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kejian

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SciRIFF-4096-0214-v2

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[ { "content": "Examine the following abstract and identify distinct entities. Focus on extracting entities related to participants, interventions, and outcomes.\n\nPresent your findings in a JSON format like: {\"Participant\": [\"example entity\", ...], \"Intervention\": [\"example entity\", ...], \"Outcome\": [\"example entity\", ...]}. If no entities are found for a category, use an empty list.\n\nAbstract Content:\n\nIntramedullary repair device against volar plating in the reconstruction of extra-articular and simple articular distal radius fractures ; a randomized pilot study . PURPOSE This prospective randomized pilot study reports our institutional experience and early results using Sonoma Wrx ( Sonoma Orthopedic Products , Santa Rosa , CA ) in the treatment of extra-articular and simple intra-articular distal radius fractures . MATERIAL AND METHODS A total of 64 patients , were enrolled in the study . They were considered eligible if they had ; unstable extra-articular distal radius fractures and simple intra-articular distal radius fractures suitable for closed reduction ( AO types ; A2.2 , A2.3 , A3.1 C2.1 , C2.2 ) . Patients in group I received intramedullary fixation using the Sonoma Wrx device and patients in group II received standard volar locking plate fixation . Radiographic criteria of acceptable healing were used for evaluation . RESULTS Two groups were similar in terms of baseline characteristics . Mean time of operation was significantly shorter in Group 1 vs. in group 2 ( 36.81 ± 7.11 vs. 48.97 ± 5.9 minutes , p = 0.001 ) . Time to healing of the fracture was not different between two groups ( 5.45 ± 1.09 vs. 5.70 ± 1.04 weeks for Group 1 vs. 2 , respectively p = 0.36 ) . Overall complications occurred in 9 patients in group 1 and in 15 patients in group 2 ( p = 0.17 ) . Follow-up was completed in all patients with a median time of 12 months and 13 months in group 1 and 2 , respectively . On radiographic evaluation radial inclination , radial height and volar tilt were not significantly different between group 1 and 2 , respectively . There were no significant differences between two groups in regard to wrist rotational degrees measured in last follow-up visit . CONCLUSION Sonoma Wrx Device is reliable and effective in terms of achieving satisfactory outcomes in treatment of distal radius fractures . It may be reasonable to use this device to prevent complications that are related to extensive soft tissue dissection .", "role": "user" }, { "content": "{\"Intervention\": [\"intramedullary fixation using the Sonoma Wrx device\", \"standard volar locking plate fixation\", \".\", \"Intramedullary repair\"], \"Outcome\": [], \"Participant\": [\"64\", \"fractures suitable\"]}", "role": "assistant" } ]

[ { "content": "Analyze the given paragraph from COVID-19 research. Determine the relevant topics discussed in the text. Your response should be a JSON array containing the identified topics. Ensure the output is a valid JSON array with no additional commentary.\n\nText:\n\nAs severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to disperse globally with worrisome speed, identifying amino acid variations in the virus could help to understand the characteristics of it. Here, we studied 489 SARS-CoV-2 genomes obtained from 32 countries from the Nextstrain database and performed phylogenetic tree analysis by clade, country, and genotype of the surface spike glycoprotein (S protein) at site 614. We found that virus strains from mainland China were mostly distributed in Clade B and Clade undefined in the phylogenetic tree, with very few found in Clade A. In contrast, Clades A2 (one case) and A2a (112 cases) predominantly contained strains from European regions. Moreover, Clades A2 and A2a differed significantly from those of mainland China in age of infected population (P = 0.0071, mean age 40.24 to 46.66), although such differences did not exist between the US and mainland China. Further analysis demonstrated that the variation of the S protein at site 614 (QHD43416.1: p.614D>G) was a characteristic of stains in Clades A2 and A2a. Importantly, this variation was predicted to have neutral or benign effects on the function of the S protein. In addition, global quality estimates and 3D protein structures tended to be different between the two S proteins. In summary, we identified different genomic epidemiology among SARS-CoV-2 strains in different clades, especially in an amino acid variation of the S protein at 614, revealing potential viral genome divergence in SARS-CoV-2 strains.", "role": "user" }, { "content": "[\"Mechanism\"]", "role": "assistant" } ]

[ { "content": "Analyze the given text to identify specific entities. Focus on extracting relevant data.\n\nProvide your findings in JSON format. Each category should list the entities found.\n\nText:\n\nLevels of PAH-DNA adducts in placental tissue and the risk of fetal neural tube defects in a Chinese population. We examined the relationship between PAH-DNA adduct levels in the placental tissue, measured by a highly sensitive (32)P-postlabeling assay, and the risk of fetal neural tube defects (NTDs). We further explored the interaction between PAH-DNA adducts and placental PAHs with respect to NTD risk. Placental tissues from 80 NTD-affected pregnancies and 50 uncomplicated normal pregnancies were included in this case-control study. Levels of PAH-DNA adducts were lower in the NTD group (8.12 per 10(8) nucleotides) compared to controls (9.92 per 10(8) nucleotides). PAH-DNA adduct concentrations below the median was associated with a 3-fold increased NTD risk. Women with a low PAH-DNA adduct level in concert with a high placental PAH level resulted in a 10-fold elevated risk of having an NTD-complicated pregnancy. A low level of placental PAH-DNA adducts was associated with an increased risk of NTDs; this risk increased dramatically when a low adduct level was coupled with a high placental PAH concentration.", "role": "user" }, { "content": "{\"Chemical\": [\"PAHs\", \"PAH\", \"(32)P\", \"nucleotides\"]}", "role": "assistant" } ]

[ { "content": "Analyze the given text and respond to the inquiry. Choose from: \"YES\", \"NO\", or \"MAYBE\".\n\nText:\n(OBJECTIVE) To evaluate the accuracy of ultrasonographic examination in boys with an undescended testis.\n(MATERIAL AND METHODS) All patients who were referred to the paediatric surgeon after detection of an undescended testis were evaluated prospectively between November 2001 and November 2004. Among these 377 patients, 87 were referred with an ultrasonogram previously prescribed by the referring primary physician. The results of the ultrasonogram were compared to the results of the clinical examination of the paediatric surgeon and, in cases of no palpable testis, to the surgical findings.\n(RESULTS) Ultrasonography did not detect the retractile testes. Ultrasonography detected 67% of the palpable undescended testes. In cases of no palpable testis, the ultrasonographic examination missed the abdominal testes and sometimes other structures were falsely interpreted as a testis.\n\nInquiry:\nIs there any interest to perform ultrasonography in boys with undescended testis?\n\nResponse:", "role": "user" }, { "content": "NO", "role": "assistant" } ]

[ { "content": "Explore the following research question and associated terms. Identify the most suitable dataset from the list provided. Use the dataset descriptions to guide your choice.\n\nInquiry: I want to train a linear classifier with the Softmax function.\n\nKeywords: classification image\n\nDataset Information:\nMNIST-1D: A minimalist, low-memory, and low-compute alternative to classic deep learning benchmarks. The training examples are 20 times smaller than MNIST examples yet they differentiate more clearly between linear, nonlinear, and convolutional models which attain 32, 68, and 94% accuracy respectively (these models obtain 94, 99+, and 99+% on MNIST).\nConvAI2: The ConvAI2 NeurIPS competition aimed at finding approaches to creating high-quality dialogue agents capable of meaningful open domain conversation. The ConvAI2 dataset for training models is based on the PERSONA-CHAT dataset.\nI-HAZE: The I-Haze dataset contains 25 indoor hazy images (size 2833×4657 pixels) training. It has 5 hazy images for validation along with their corresponding ground truth images.\nCIFAR-10: The CIFAR-10 dataset (Canadian Institute for Advanced Research, 10 classes) is a subset of the Tiny Images dataset and consists of 60000 32x32 color images. The images are labelled with one of 10 mutually exclusive classes: airplane, automobile (but not truck or pickup truck), bird, cat, deer, dog, frog, horse, ship, and truck (but not pickup truck).\n\nAvailable Datasets: A: MNIST-1D B: ConvAI2 C: I-HAZE D: CIFAR-10", "role": "user" }, { "content": "CIFAR-10", "role": "assistant" } ]

[ { "content": "Review the provided collection of medical RCT summaries. Your objective is to distill the essential insights into a brief conclusion. Focus solely on the synthesis of findings without additional commentary. The RCT summaries are as follows:\n\n\n\nReport Title 1:\nEffects of reducing insemination time in human in vitro fertilization and embryo development by using sibling oocytes.\nReport Abstract 1:\nRecent studies showed a beneficial effect of reducing the time of sperm-oocyte interaction on fertilization, division, and implantation rates of the oocytes obtained from randomized patients. In the present study, the effects of reduced insemination time on fertilization and embryo development were evaluated by using sibling oocytes from the same patient.\n A total of 464 oocytes from 36 patients was randomly allocated to be inseminated for either 1 hr (reduced) or 18 hr (regular).\n Fertilization rates were not significantly different between reduced (135/229; 59%) and regular (150/235; 64%) groups. Cleavage rates and embryo quality were similar in both groups. A total of 135 embryos (73 from the reduced and 62 from the regular group) was transferred to 36 patients. Thirty-four embryos implanted in 18 patients (25.2% implantation and 50.0% pregnancy rates).\n Fertilization, cleavage, and embryo development from 1-hr insemination is comparable, not superior, to those from an 18-hr insemination time, which is commonly used in in vitro fertilization programs. These data suggest that reduced insemination time can be used during in vitro fertilization to avoid unnecessarily longer exposure to spermatozoa.\n\n\nReport Title 2:\nProlonged sperm-oocyte exposure and high sperm concentration affect human embryo viability and pregnancy rate.\nReport Abstract 2:\nA reduced time interval of oocyte exposure to spermatozoa was investigated to assess whether it could enhance oocyte development and improve embryo viability, especially in cases of male factor infertility. A total of 167 patients were included in a prospective randomized study. They were randomly allocated to two major study groups, A (n = 85) and B (control group; n = 82). The oocytes from group A patients were exposed to spermatozoa for only 1 h; those from group B were exposed for 16 h. The two study groups were then subdivided according to semen quality for further analysis of the results. Significantly higher percentages were obtained in group A than in group B in terms of the fertilization rate (74 versus 68%, P < 0.025), cleavage rate (53 versus 41%, P < 0.005), pregnancy rate (27 versus 12%, P < 0.05) and implantation rate (11 versus 6%, P < 0.05). In addition, an increased fertilization rate was achieved in oocytes exposed to male factor spermatozoa for only 1 h compared with the conventional incubation period (78 versus 65%, P < 0.01). Advanced cellular stages (55 versus 41%, P < 0.02) and higher implantation rates (13 versus 4%, P < 0.05) were attained in the subgroup whose oocytes were exposed to normal spermatozoa for 1 h compared with the male factor spermatozoa with the standard culture interval. The higher fertilization rates, enhanced embryo development and viability achieved in group A indicate that prolonged exposure of oocytes to high concentrations of spermatozoa is detrimental, decreasing sperm-oocyte interaction and subsequent embryo implantation, particularly in male factor patients.\n\n\nReport Title 3:\nShortened exposure of oocytes to spermatozoa improves in-vitro fertilization outcome: a prospective, randomized, controlled study.\nReport Abstract 3:\nA prospective, randomized study of 158 patients undergoing in-vitro fertilization (IVF) and embryo transfer was conducted to evaluate whether a shortened exposure of oocytes to spermatozoa enhances oocyte development, and subsequently influences the IVF outcome. A comparison was made between conventional treatment time and shorter exposure of retrieved oocytes to spermatozoa. Fertilization and cleavage rates, embryo quality, implantation and pregnancy rates in the study group (short exposure) versus controls (standard IVF procedure) were evaluated. Fertilization (56 versus 61%) and cleavage rates (96 versus 92%) were similar in the two groups respectively. However, embryo quality was significantly higher in the study group (P < 0.05). Moreover, the pregnancy and implantation rates were significantly increased (42.4 versus 26% per embryo transfer, and 16 versus 10% respectively; P < 0.05). Our results demonstrated that shorter exposure of oocytes to spermatozoa is superior to the standard time in IVF and may have a favourable effect on implantation rates by improving embryo quality.\n\n\nReport Title 4:\nA prospective randomized controlled study of the effect of short coincubation of gametes during insemination on zona pellucida thickness.\nReport Abstract 4:\nA prospective, randomized study was conducted to evaluate the thickness, of zona pellucida (ZP) after brief or standard exposure of human oocytes to spermatozoa, and to determine the correlation between ZP thickness, fertilization rate and embryo quality. The mean ZP thickness 48 h after insemination was found to be significantly less in fertilized oocytes than in non-fertilized oocytes in all treated groups (13.72 +/- 3.0 microns and 15.08 +/- 2.5 microns, respectively; p < 0.007). Zona pellucida thickness correlated positively with embryo quality. Brief exposure of gametes was found to influence ZP thickness. The ZP was significantly thinner after brief and intracytoplasmic sperm injection (ICSI) exposure of oocytes to spermatozoa than after standard in vitro fertilization (IVF). The mean ZP thickness 24 and 48 h after fertilization was significantly greater in standard IVF (16.43 +/- 2.8 microns and 15.22 +/- 2.7 microns, respectively) than in either the brief exposure or ICSI groups (12.78 +/- 2.4 microns and 13.01 +/- 3.5 microns vs. 13.46 +/- 2.2 microns and 13.16 +/- 2.4 microns; p < 0.0001).\n\n\nReport Title 5:\nThe effects of brief gamete co-incubation in human in vitro fertilization.\nReport Abstract 5:\nTo investigate whether very short exposure of mature oocytes to sperm in vitro may affect the fertilization rates, embryo cleavage rates, and embryo quality between sibling oocytes in the same patient.\n Sibling oocytes of the same patient from 23 oocyte collection cycles were randomly allocated to the study group, with a 1-hr or 3-hr sperm-oocyte incubation, or the control group with the standard overnight gamete co-incubation. The fertilization rates, cleavage rates, and subsequent embryo quality were evaluated.\n Our results showed no statistically significant differences in fertilization rates, embryo cleavage rates, and quality of the embryos between the study group and the control group.\n Since the present study showed that long exposure of the oocyte to sperm has no advantage over short exposure, we prefer shortening the oocyte-sperm incubation period for reducing the negative effect induced by nonphysiologically high concentrations of spermatozoa.\n\n\nReport Title 6:\nShort coincubation of gametes in in vitro fertilization improves implantation and pregnancy rates: a prospective, randomized, controlled study.\nReport Abstract 6:\nTo examine the benefits of short coincubation of gametes compared to prolonged incubation in in vitro fertilization (IVF).\n Prospective randomized controlled study.\n Hospital-based fertility center.\n One hundred thirty patients (group 1) and 129 patients (group 2).\n Oocytes from group 1 were exposed to spermatozoa for 2 hours, and oocytes from group 2 were exposed to spermatozoa for 20 hours.\n Fertilization and cleavage rates, embryo quality, and pregnancy and implantation rates were evaluated. Estradiol (E(2)) and progesterone (P(4)) levels were measured in the wells of culture dishes after 2-hour exposure of oocytes/zygotes to spermatozoa in group 1 and after 20-hour exposure in both the groups.\n There was no difference between the two groups in the fertilization rate and the number of embryos obtained. However, the proportion of grade 1 embryos was significantly higher among group 1 compared to group 2 patients. Clinical pregnancy and implantation rates were significantly higher among group 1 compared to group 2. The significantly higher levels of E(2) and P(4) in the 20-hour cultures compared with the 2-hour cultures may have been detrimental to embryo quality, pregnancy, and implantation rates.\n Coincubation of gametes for 2 hours with standard or high insemination concentrations of spermatozoa significantly improved embryo quality and the pregnancy and implantation rates compared with overnight incubation of gametes.\n\n\nReport Title 7:\nExtending the coincubation time of gametes improves in vitro fertilization.\nReport Abstract 7:\nnan", "role": "user" }, { "content": "This review has provided evidence that brief co-incubation of sperm and oocytes may improve the ongoing pregnancy and clinical pregnancy rates for infertile women undergoing IVF cycles. More RCTs are required to assess whether brief co-incubation would contribute to a higher live birth rate and a lower miscarriage rate compared to the standard overnight insemination protocol.", "role": "assistant" } ]

[ { "content": "Examine the citation provided below. Determine the primary purpose of this citation within the context of the research paper. \n\nCitation:\n\nAs for rs846910, a haplotype containing the A allele has been previously shown to be associated with higher HSD11B1 mRNA levels and activity in the adipose tissue of southern European whites (Gambineri et al., 2011).", "role": "user" }, { "content": "Result", "role": "assistant" } ]

[ { "content": "Examine the following abstract and identify distinct entities. Focus on extracting entities related to participants, interventions, and outcomes.\n\nPresent your findings in a JSON format like: {\"Participant\": [\"example entity\", ...], \"Intervention\": [\"example entity\", ...], \"Outcome\": [\"example entity\", ...]}. If no entities are found for a category, use an empty list.\n\nAbstract Content:\n\nInfluence of infusion time on the acute toxicity of amphotericin B : results of a randomized double-blind study .", "role": "user" }, { "content": "{\"Intervention\": [\"amphotericin B\"], \"Outcome\": [\"acute toxicity of amphotericin B :\"], \"Participant\": [\"acute toxicity of amphotericin B\", \"infusion time\"]}", "role": "assistant" } ]

[ { "content": "Examine the abstracts provided from a main scientific article and its cited works. Craft a narrative that synthesizes the key insights and contributions, emphasizing their interconnections. Employ numerical citations such as [1], [2], etc., to reference the cited works.\n\nMain Article Summary:\nText-entry aims to provide an effective and efficient pathway for humans to deliver their messages to computers. With the advent of mobile computing, the recent focus of text-entry research has moved from physical keyboards to soft keyboards. Current soft keyboards, however, increase the typo rate due to lack of tactile feedback and degrade the usability of mobile devices due to their large portion on screens. To tackle these limitations, we propose a fully imaginary keyboard (I-Keyboard) with a deep neural decoder (DND). The invisibility of I-Keyboard maximizes the usability of mobile devices and DND empowered by a deep neural architecture allows users to start typing from any position on the touch screens at any angle. To the best of our knowledge, the eyes-free ten-finger typing scenario of I-Keyboard which does not necessitate both a calibration step and a predefined region for typing is first explored in this work. For the purpose of training DND, we collected the largest user data in the process of developing I-Keyboard. We verified the performance of the proposed I-Keyboard and DND by conducting a series of comprehensive simulations and experiments under various conditions. I-Keyboard showed 18.95 and 4.06 increases in typing speed (45.57 WPM) and accuracy (95.84 ), respectively over the baseline.\n\nCited Works Summary:\n[1]: Touch screen surfaces large enough for ten-finger input have become increasingly popular, yet typing on touch screens pales in comparison to physical keyboards. We examine typing patterns that emerge when expert users of physical keyboards touch-type on a flat surface. Our aim is to inform future designs of touch screen keyboards, with the ultimate goal of supporting touch-typing with limited tactile feedback. To study the issues inherent to flat-glass typing, we asked 20 expert typists to enter text under three conditions: (1) with no visual keyboard and no feedback on input errors, then (2) with and (3) without a visual keyboard, but with some feedback. We analyzed touch contact points and hand contours, looking at attributes such as natural finger positioning, the spread of hits among individual keys, and the pattern of non-finger touches. We also show that expert typists exhibit spatially consistent key press distributions within an individual, which provides evidence that eyes-free touch-typing may be possible on touch surfaces and points to the role of personalization in such a solution. We conclude with implications for design.\n\n[2]: Touch typing on flat surfaces (e.g. interactive tabletop) is challenging due to lack of tactile feedback and hand drifting. In this paper, we present TOAST, an eyes-free keyboard technique for enabling efficient touch typing on touch-sensitive surfaces. We first formalized the problem of keyboard parameter (e.g. location and size) estimation based on users' typing data. Through a user study, we then examined users' eyes-free touch typing behavior on an interactive tabletop with only asterisk feedback. We fitted the keyboard model to the typing data, results suggested that the model parameters (keyboard location and size) changed not only between different users, but also within the same user along with time. Based on the results, we proposed a Markov-Bayesian algorithm for input prediction, which considers the relative location between successive touch points within each hand respectively. Simulation results showed that based on the pooled data from all users, this model improved the top-1 accuracy of the classical statistical decoding algorithm from 86.2 to 92.1 . In a second user study, we further improved TOAST with dynamical model parameter adaptation, and evaluated users' text entry performance with TOAST using realistic text entry tasks. Participants reached a pick-up speed of 41.4 WPM with a character-level error rate of 0.6 . And with less than 10 minutes of practice, they reached 44.6 WPM without sacrificing accuracy. Participants' subjective feedback also indicated that TOAST offered a natural and efficient typing experience.\n\n[3]: Text entry rates are explored for several variations of soft keyboards. We present a model to predict novice and expert entry rates and present an empirical test with 24 subjects. Six keyboards were examined: the Qwerty, ABC, Dvorak, Fitaly, JustType, and telephone. At 8-10 wpm, novice predictions are low for all layouts because the dominant factor is the visual scan time, rather than the movement time. Expert predictions are in the range of 22-56 wpm, although these were not tested empirically. In a quick, novice test with a representative phrase of text, subjects achieved rates of 20.2 wpm (Qwerty), 10.7 wpm (ABC), 8.5 wpm (Dvorak), 8.0 wpm (Fitaly), 7.0 wpm (JustType), and 8.0 wpm (telephone). The Qwerty rate of 20.2 wpm is consistent with observations in other studies. The relatively high rate for Qwerty suggests that there is skill transfer from users' familiarity with desktop computers to the stylus tapping task.\n\n[4]: On a touchscreen keyboard, it can be difficult to continuously type without frequently looking at the keys. One factor contributing to this difficulty is called hand drift, where a user's hands gradually misalign with the touchscreen keyboard due to limited tactile feedback. Although intuitive, there remains a lack of empirical data to describe the effect of hand drift. A formal understanding of it can provide insights for improving soft keyboards. To formally quantify the degree (magnitude and direction) of hand drift, we conducted a 3-session study with 13 participants. We measured hand drift with two typing interfaces: a visible conventional keyboard and an invisible adaptive keyboard. To expose drift patterns, both keyboards used relaxed letter disambiguation to allow for unconstrained movement. Findings show that hand drift occurred in both interfaces, at an average rate of 0.25mm min on the conventional keyboard and 1.32mm min on the adaptive keyboard. Participants were also more likely to drift up and or left instead of down or right.\n\n[5]: Eyes-free input is desirable for ubiquitous computing, since interacting with mobile and wearable devices often competes for visual attention with other devices and tasks. In this paper, we explore eyes-free typing on a touchpad using one thumb, wherein a user taps on an imaginary QWERTY keyboard while receiving text feedback on a separate screen. Our hypothesis is that users can transfer their typing ability obtained from visible keyboards to eyes-free use. We propose two statistical decoding algorithms to infer users’ eyes-free input: the absolute algorithm and the relative algorithm. The absolute algorithm infers user input based on the absolute position of touch endpoints, while the relative algorithm infers based on the vectors between successive touch endpoints. Evaluation results showed users could achieve satisfying performance with both algorithms. Text entry rate was 17-23 WPM (words per minute) depending on the algorithm used. In comparison, a baseline cursor-based text entry method yielded only 7.66 WPM. In conclusion, our research demonstrates for the first time the feasibility of thumb-based eyes-free typing, which provides a new possibility for text entry on ubiquitous computing platforms such as smart TVs and HMDs.", "role": "user" }, { "content": "A number of works have attempted to understand the user behavior with ten finger typing with soft keyboards. The major findings are as follows: : The typing speed with soft keyboards drops dramatically compared to the speed with physical keyboards [3] . : The distribution of touch points resembles the mechanical keyboard layout [1] , though the distribution varies over time in shape and size [2] . : Hand-drift occurs over time and becomes stronger for invisible keyboards [4] . : Various factors cause tap variability among users [5] . The factors include finger volume, hand posture and mobility.", "role": "assistant" } ]

[ { "content": "Read the provided biomedical research paper and create a concise abstract. Ensure the abstract captures the main points of the paper.\n\nFull Paper:\nchoriocarcinoma is a highly malignant gestational trophoblastic disease associated with high urine and serum -hcg levels .\nto date , few studies have reported pulmonary embolism ( pe ) and pulmonary hypertension caused by choriocarcinoma of the pulmonary artery . here , we report a young female patient with choriocarcinoma of the pulmonary artery who was clinically misdiagnosed with pulmonary thromboembolism ( pte ) and died of acute cardiopulmonary failure very soon after embolectomy .\na 25 year - old female patient first experienced an episode of sudden dyspnea and frequent coughing after routine physical activity .\nshe was initially diagnosed at a local hospital with acute pneumonia based on a chest x - ray , which showed several small , scattered radio - opaque shadows on both lungs .\nsix months later , the patient was referred to our hospital because of severe orthopnea . upon arrival\n, arterial blood gas analysis showed that the values of ph , paco2 , and pao2 were 7.502 , 26.3 mmhg , and 50 mmhg , respectively , under 2 l / minute oxygen inhalation .\nan emergent contrast - enhanced ct scan showed occlusion of the left pulmonary artery and right inferior pulmonary artery ( fig .\nthe scan further revealed multiple patchy , cord - like , nodular fuzzy shadows in bilateral lungs ( fig .\nmeanwhile , a diagnosis of pe was made based on echocardiographs , which revealed severe pulmonary hypertension ( pulmonary systolic pressure , 105 mmhg ) and mild tricuspid regurgitation .\nalthough her d - dimer test value was only 0.27 g / ml , a pulmonary angiograph was still performed via the right femoral vein , which showed complete occlusion of the left pulmonary artery and right inferior pulmonary artery .\na : ct scan demonstrates occlusion of the left pulmonary artery and right inferior pulmonary artery .\nb : ct scan shows multiple patchy , cordlike , nodular fuzzy shadows in bilateral lungs .\nthe patient claimed that she was a non - smoker , did not use oral contraception , and had experienced three previous spontaneous abortions ( the most recent occurring one year previously ) .\nthe patient had spent more than 10 hours playing card games every day during the past four years .\nan angiographic procedure for direct injection of 400,000 iu urokinase failed to dissolve the emboli . since her pe was believed to have derived from deep venous thrombi ( sedentary clinical history ) , a filter was also placed in the inferior vena cava .\nthe condition of the patient continued to deteriorate with progressive tachypnea , cyanosis , non - productive cough , and hemoptysis ; therefore , a pulmonary embolectomy was carried out using a cardiopulmonary bypass procedure .\ncomplete obstruction of the openings of the left pulmonary artery and right inferior pulmonary artery by the yellow - pink soft emboli was observed .\nthe emboli were completely removed to re - establish blood flow from the bronchial artery . at the time of re - warming\nprior to decannulation , the pulmonary artery systolic pressure ranged from 90 - 110 mmhg and surpassed the aortic systolic pressure .\nthe hemodynamic situation was so unstable that a 5 mm hole was made in the atrial septum to mitigate the condition .\nthe patient was then transferred to the cardio - thoracic intensive care unit . in spite of intensive efforts ,\nthe patient ultimately succumbed to cardiopulmonary failure and acute renal failure approximately 14 hours after embolectomy .\npathologic evaluation of pulmonary emboli showed macroscopic fragments of yellow - pink tissue measuring 4 cm at the greatest dimension ( fig .\npost - mortem histological evaluation showed that the viable tumor constituted only a thin peripheral rim with a central area of necrosis and focal hemorrhage ( fig .\nthe tumor cells consisted of an intimate amalgamation of multinucleate syncytiotrophoblasts , mononucleate cytotrophoblasts , and intermediate trophoblasts .\nthere was considerable cytological atypia in the trophoblasts with hyperchromatic nuclei and abnormal mitotic figures ( fig .\nlack of villi and new blood vessel formation comprised the unique morphological features consistent with choriocarcinoma .\nimmunohistochemical staining demonstrated strong reactivity for hcg in syncytiotrophoblasts ( fig . 2c ) and strong cytokeratin positivity was observed in all the tumor cells ( fig .\nthe diagnosis of choriocarcinoma embolism was confirmed . a : macroscopic examination of the yellow - pink soft embolus obtained during pulmonary embolectomy .\nb : tumor characterized by atypical trophoblasts with polymorphic and hyperchromatic nuclei as well as abnormal mitotic figures .\nchoriocarcinoma of the pulmonary artery has been described as a rare cause of pe and pulmonary artery hypertension ( pah ) .\nsuch cases represent a potentially fatal emergency due to cardiopulmonary failure . however , the diagnosis is difficult to establish because of the tendency of these tumors to present characteristics of more common diseases such as pte .\nalmost all choriocarcinomas of the pulmonary artery present with pe , and pah occurs after nonmolar abortions ( mostly spontaneous abortions ) and rarely after normal pregnancies .\nthe low incidence of choriocarcinoma of the pulmonary artery and the long latency after a live birth or nonmolar abortion make early diagnosis of this condition very challenging .\nbagshawe first reported choriocarcinoma of the pulmonary arteries , identified at necropsy in patients who died of pah in 1959 .\nhe suggested that choriocarcinoma emboli could be the result of a progressive neoplastic obstruction of pulmonary arteries leading to pah and respiratory distress .\nin addition to the case reported here , we reviewed 10 cases of pulmonary choriocarcinoma presenting with pe and pah reported between 1991 and 2008 ; the findings of these 11 cases are summarized in table 1 .\nalmost all of the patients ( 10/11 ) had a history of abortion with latency periods ranging from two months to six years and no primary uterine tumor identified . among these cases ,\nseven ( 7/10 ) were spontaneous abortion and , only one patient ( 1/11 ) a normal delivery three years previously .\nthe most important risk factor , a history of hydatidiform mole , was absent from the cases included in our review ; almost all cases occur after a spontaneous abortion and rarely after normal full term pregnancy . owing to regular check - ups for potential malignant sequelae after hydatidiform molar pregnancies , few of these patients present with advanced disease , such as pulmonary hypertension\n. therefore , almost all trophoblastic tumors that occur after a normal pregnancy are choriocarcinomas .\ne : etoposide ; m : methotrexate ; a : actinomycin d / dactinomycin ; v : vincristine ; cyc : cyclophosphamide ; car : carboplatin ; cis : cisplatin ; aned : alive with no evidence of disease ; dod : dead of disease ; na : not available ; pe : pulmonary embolism ; pte : pulmonary thromboembolism ; mcc : metastatic choriocarcinoma ; el : embolectomy .\n. almost all results of pelvic ultrasound and gynecologic examination of the uteri and ovaries were negative , even by autopsy .\nrare cases of pe due to choriocarcinoma in women occurring many years after hysterectomy have been reported .\nmoreover , tanimura and colleagues revealed trophoblasts in the pulmonary arteries in autopsies of nine of ten patients who died after delivery or abortion .\ntherefore , it has been speculated that primary choriocarcinoma of the pulmonary arteries in women may be due to malignant transformation of normal villous trophoblasts which entered the pulmonary artery at the time of abortion or delivery ; however , the others consider that pulmonary choriocarcinoma derives metastatically from a regressed tumor previously present in the uterus .\nsimilar to our case , patients commonly present with non - specific symptoms such as chest pain , cough and dyspnea , as well as abnormal findings of chest x - rays ( diffuse radiopaque shadows in the bilateral lungs ) .\nthese manifestations are commonly misdiagnosed as pneumonia due to the absence of molar pregnancy history and gynecologic symptoms .\nas the quantity and volume of the pulmonary artery embolus increases , symptoms of pulmonary hypertension are present .\nchest ct imaging may show intraluminal contrast filling defects ( emboli ) in the pulmonary artery down to the segmental and subsegmental levels , as well as multiple peripheral opacities in both lungs . at this stage ,\nthoracic surgeons frequently misdiagnosed the condition as pulmonary thromboembolism and as a result , the duration from onset to treatment ranged from one to 12 months ( average 6 months ) . typically , serum -hcg levels in patients with choriocarcinoma of the pulmonary artery are high , ranging from 1,000 miu / ml to over 1,000,000 miu / ml , and urine pregnancy tests are always positive . in most developed countries , urine and/or\nserum -hcg evaluation is a routine screening test in female patients regardless of the disorders that bring them to clinics .\nhowever , there are still many hospitals around the world ( especially in developing countries ) in which urine and/or serum -hcg is still not on the list of routine tests .\nsimilarly , the clinician responsible for the case described here noted the long sedentary history of the patient but disregarded the three spontaneous abortions ; therefore , urine and/or serum -hcg tests were consistently omitted .\nthus , urine and/or serum -hcg test should always be a frontline test ordered when female patients present with the symptoms of pe and pah to rule out the possibility of choriocarcinoma .\nseckl and coworkers reported three cases of young women with complete remission following chemotherapy of choriocarcinoma embolism .\nthe diagnosis was based mainly on high -hcg levels in non - pregnant women , indicating that a definitive histological diagnosis is not essential before initiation of chemotherapy , particularly since surgery is associated with considerable morbidity .\nrecently , fdg - pet / ct has been utilized to assist diagnosis for increased metabolism of the embolus .\nmultiagent chemotherapy includes etoposide , methotrexate , actinomycin d , cyclophosphamide , cisplatin , vincristine , and dactinomycin , leading to a cure rate in excess of 89% .\nthus , chemotherapy coupled with biochemical and radiological monitoring constitutes an attractive management approach for pulmonary choriocarcinoma embolism therapy . in conclusion ,\npulmonary choriocarcinoma embolism is now a curable disease which is commonly associated with spontaneous abortion , a long latency and empty uteri . in order to avoid unnecessary deaths , it is very important for the clinician to recognize the non - specific clinical characteristics in the early stages and to use urine and/or serum -hcg as the frontline test in the fertile female patients who are clinically suspected of pe ; the earlier the diagnosis and initiation of chemotherapy , the better the prognosis .", "role": "user" }, { "content": "abstractcases of pulmonary embolism and pulmonary artery hypertension caused by choriocarcinoma represent a rare clinical emergency . \n we report a case of a 25-year - old woman who presented with pulmonary embolism and hypertension and died soon after complete pulmonary embolectomy . \n a related literature review revealed that almost all of these patients had previously experienced a spontaneous abortion ( average , 6 months ) and were not pregnant .", "role": "assistant" } ]

[ { "content": "Review the following segment from a research document in AI. Answer the subsequent query based solely on the provided information. Limit your response to the answer itself.\n\nResearch Segment: Besides a straightforward integration, we have also studied whetherInception itself can be made more efficient by making it deeper and wider.For that purpose, we designed a new version named Inception-v4which has a more uniform simplified architecture and more inception modulesthan Inception-v3. Historically, Inception-v3 had inherited a lot of thebaggage of the earlier incarnations. The technical constraints chiefly came fromthe need for partitioning the model for distributed training usingDistBelief [2].Now, after migrating our training setup to TensorFlow [1]these constraints have been lifted, which allowed us to simplify the architecturesignificantly. The details of that simplified architecture are described in Section 3.\n\nInquiry: Why does inception-v4’s inception module use average pooling instead of max pooling?", "role": "user" }, { "content": "One possible reason to use average pooling instead of max pooling is that max pooling introduces some kind of technical constraints which are reduced by average pooling. But these constraint have not been explained in the paper. So this question cannot be fully answered in this paper.", "role": "assistant" } ]

[ { "content": "Review the provided sections from a computer science paper and distill the primary contribution into a single sentence. Provide only the summary sentence.\n\nSections:\n\nState-of-the-art deep neural networks (DNNs) typically have tens of millions of parameters, which might not fit into the upper levels of the memory hierarchy, thus increasing the inference time and energy consumption significantly, and prohibiting their use on edge devices such as mobile phones.\nThe compression of DNN models has therefore become an active area of research recently, with \\emph{connection pruning} emerging as one of the most successful strategies.\nA very natural approach is to prune connections of DNNs via $\\ell_1$ regularization, but recent empirical investigations have suggested that this does not work as well in the context of DNN compression.\nIn this work, we revisit this simple strategy and analyze it rigorously, to show that:\n(a) any \\emph{stationary point} of an $\\ell_1$-regularized layerwise-pruning objective has its number of non-zero elements bounded by the number of penalized prediction logits, regardless of the strength of the regularization;\n(b) successful pruning highly relies on an accurate optimization solver, and there is a trade-off between compression speed and distortion of prediction accuracy, controlled by the strength of regularization.\nOur theoretical results thus suggest that $\\ell_1$ pruning could be successful provided we use an accurate optimization solver.\nWe corroborate this in our experiments, where we show that simple $\\ell_1$ regularization with an Adamax-L1(cumulative) solver gives pruning ratio competitive to the state-of-the-art.\nState-of-the-art Deep Neural Networks (DNNs) typically have millions of parameters.\nFor example, the VGG-16 network BID0 ), from the winning team of ILSVRC-2014, contains more than one hundred million parameters; inference with this network on a single image takes tens of billions of operations, prohibiting its use on edge devices such as mobile phones or in real-time applications.\nIn addition, the huge size of DNNs often precludes them from being placed at the upper level of the memory hierarchy, with resulting slow access times and expensive energy consumption.A recent thread of research has thus focused on the question of how to compress DNNs.\nOne successful approach that has emerged is to trim the connections between neurons, which reduces the number of non-zero parameters and thus the model size BID1\nb) ; BID3 ; BID4 ; BID5 ; BID6 ; BID7 ).\nHowever, there has been a gap between the theory and practice: the trimming algorithms that have been practically successful BID1\nb) ; BID3 ) do not have theoretical guarantees, while theoretically-motivated approaches have been less competitive compared to the heuristics-based approaches BID5 , and often relies on stringent distributional assumption such as Gaussian-distributed matrices which might not hold in practice.\nWith a better theoretical understanding, we might be able to answer how much pruning one can achieve via different approaches on different tasks, and moreover when a given pruning approach might or might not work.\nIndeed, as we discuss in our experiments, even the generally practically successful approaches are subject to certain failure cases.\nBeyond simple connection pruning, there have been other works on structured pruning that prune a whole filter, whole row, or whole column at a time BID8 ; BID9 ; BID10 ; ; BID12 ).\nThe structured pruning strategy can often speed up inference speed at prediction time more than simple connection pruning, but the pruning ratios are typically not as high as non-structured connection pruning; so that the storage complexity is still too high, so that the caveats we noted earlier largely remain.A very natural strategy is to use 1 regularized training to prune DNNs, due to their considerable practical success in general sparse estimation in shallow model settings.\nHowever, many recent investigations seemed to suggest that such 1 regularization does not work as well with non-shallow DNNs, especially compared to other proposed methods.\nDoes 1 regularization not work as well in non-shallow models?\nIn this work, we theoretically analyze this question, revisit the trimming of DNNs through 1 regularization.\nOur analysis provides two interesting findings:\n(a) for any stationary point under 1 regularization, the number of non-zero parameters in each layer of a DNN is bounded by the number of penalized prediction logits-an upper bound typically several orders of magnitude smaller than the total number of DNN parameters, and\n(b) it is critical to employ an 1 -friendly optimization solver with a high precision in order to find the stationary point of sparse support.Our theoretical findings thus suggest that one could achieve high pruning ratios even via 1 regularization provided one uses high-precision solvers (which we emphasize are typically not required if we only care about prediction error rather than sparsity).\nWe corroborate these findings in our experiments, where we show that solving the 1 -regularized objective by the combination of SGD pretraining and Adamax-L1(cumulative) yields competitive pruning results compared to the state-ofthe-art.\nIn this work, we revisit the simple idea of pruning connections of DNNs through 1 regularization.\nWhile recent empirical investigations suggested that this might not necessarily achieve high sparsity levels in the context of DNNs, we provide a rigorous theoretical analysis that does provide small upper bounds on the number of non-zero elements, but with the caveat that one needs to use a high-precision optimization solver (which is typically not needed if we care only about prediction error rather than sparsity).\nWhen using such an accurate optimization solver, we can converge closer to stationary points than traditional SGD, and achieve much better pruning ratios than SGD, which might explain the poorer performance of 1 regularization in recent investigations.\nWe perform experiments across different datasets and networks and demonstrate state-of-the-art result with such simple 1 regularization.\nTable 5 : Per-layer Resnet-32 architecture.\nThere are 3 main convolutional blocks with downsampling through stride=2 for the first layer of each block.\nAfter the convloutional layers, global pooling is applied on the spatial axes and a fully-connected layer is appended for the output.\nEach set of rows is a residual block.", "role": "user" }, { "content": "We revisit the simple idea of pruning connections of DNNs through $\\ell_1$ regularization achieving state-of-the-art results on multiple datasets with theoretic guarantees.", "role": "assistant" } ]

[ { "content": "Read the provided biomedical research paper and create a concise abstract. Ensure the abstract captures the main points of the paper.\n\nFull Paper:\nthe disrupted in schizophrenia 1 ( disc1 ) gene is a 414.3 kb gene located on chromosomal region 1q42.2 , and consists of 13 exons .\ndisc1 was originally identified as a candidate gene for schizophrenia in a large scottish family , in which a balanced translocation involving chromosomes 1 and 11 was strongly linked to schizophrenia , schizoaffective disorder , bipolar affective disorder , and recurrent , major depression . in this family\n, carriers of the translocation were found to have reduced p300 amplitude , which is observed in some patients with schizophrenia .\nsubsequent association studies identified numerous polymorphisms in the disc1 gene associated with schizophrenia and affective disorders , although different , polymorphisms / haplotypes in various regions of the gene were implicated in these studies . \n in the adult mouse brain ,\ndisc1 is expressed widely , including in the olfactory bulb , cortex , hippocampus , hypothalamus , cerebellum , and brain stem . during development ,\ndisc1 protein is detected at all stages , from embryonic day 10 ( elo ) to 6 months old , with two significant peaks of protein expression of one of the disc1 isoforms at e13.5 and postnatal day 35 .\ninterestingly , these time points correspond to periods of active neurogenesis and puberty in the mouse .\nthese results suggest , that disc1 may play a critical role in brain development , lending support to the neurodevelopmental hypothesis of schizophrenia . \n\ndisc1 encodes an 854-amino acid ( aa ) protein , which shows no homology to other known proteins and little homology between species .\nthis amino - acid sequence predicts that the protein disc1 may act as a scaffolding protein with multiple binding motifs , facilitating formation of protein complexes .\nthe n -terminus ( aa 1 - 347 ) contains nuclear localization signals , whereas the c - terminus ( aa 348 - 854 ) appears to be important , for microtubule and centrosomal targeting,17 - 19 although no centrosomal localization has been detected so far for the native protein .\nalthough the precise function of disc1 in the brain is unknown , a number of disc1 -interacting partners have been identified , including fasciculation and elongation protein zeta-1 ( fez1 ) , nuclear distribution element - like ( nudel ) , and lissencephaly 1 ( lis1 ) , which are known to play a role in neuronal development and functioning .\naltered interactions between disc1 and its binding partners are currently being investigated in order to understand more accurately the biology of disc1 as a schizophrenia susceptibility gene .\nin an effort to understand the cellular function of disc1 , yeast - two hybrid studies have been used to identify molecular interactors of disc1 .\nit , was found that , disc1 has numerous binding partners , including nudel , fez1 , activating transcription factor ( att ' ) 4/5 , and microtubule - associated protein 1 a ( mapi a ) .\nnudel is a component of a pathway involved in cytoplasmic dynein movement , and is involved in neurofilament assembly , neuronal migration , and development of neurite morphology .\noverexpression of truncated disc1 protein inhibits neurite outgrowth in pci 2 cells , suggesting that the disc1-nudel complex may be involved in neuronal outgrowth .\nthe hypothetical peptide product , resulting from the scottish translocation removes the interaction domain for nudel .\nrecently , it has been shown that nudel oligopeptidase activity is under tight , regulation through binding to disc1 , since a mutation very close to the disc1-binding site of nudel abolishes this activity .\ninterestingly , nudel cleaves a number of neuropeptides in vitro , some of which have previously been implicated in the pathophysiology of schizophrenia , including neurotensin ( nt ) .\nnt receptor agonists may be potential antipsychotics ; thus , inhibition of nudel could lead to increase in local concentration of nt , which may have an antipsychotic effect .\naltered subcellular distribution of disc1 has been reported in patients with psychosis and alcohol / substance abuse , with increased ratios of nuclear to cytoplasmic disc1 protein levels in patients .\ncell culture studies in cortical neurons have found evidence that disc1 may colocalize with mitochondrial markers , and that its subcellular targeting is independent of the nudel - binding site .\nhayashi et al have also demonstrated that disc1 and nudel bind in a neurodevelopmentally regulated manner and form a trimolecular complex with another protein , lis1 .\nlis1 is involved in neuronal migration and corticogenesis . although the function of this complex is currently unknown , it .\nanother interacting partner of disc1 is fez1 , which is a mammalian homologue of the caenorhabditis elegans unc-76 protein , involved in axonal outgrowth and fasciculation .\nmiyoshi et al demonstrated that disc1 participates in neurite extension through its c - terminal interaction with fez1 .\nthe chromosomal location for fez1 was previously implicated in a schizophrenia linkage analysis , although results from different , populations vary in significance .\na modest association between schizophrenia and fez1 polymorphisms has been detected in a subset of japanese patients . \n\nin our laboratory , we have tested the hypothesis that , altered expression of disc1 , and/or its molecular partners nudel , fez1 , and lis1 may underlie its pathogenic role in schizophrenia and explain its genetic association .\nwe examined the expression of disc1 and these selected binding partners in postmortem human brain .\nwe found no difference in the expression of disc1 mrna in schizophrenia , and no association with previously identified risk snps ( all f values < 1.5 , all p values > 0.2 ) .\ndisc1 immunoreactivity was significantly , albeit modestly ( by approximately 20% ) , increased in the hippocampus of patients with schizophrenia : f(1,73)=3.6 , p=0.05 .\nhowever , the expression of nudel , fez1 , and lis1 mrna was each significantly reduced in schizophrenic tissue in both the dorsolateral prefrontal cortex and hippocampus and the expression of each gene showed association with a high risk disc1 polymorphism ( all p values < 0.05 ) .\nthese data implicate genetically linked abnormalities in the disc1 molecular pathway in the pathophysiology of schizophrenia . given its role in brain development and plasticity via .\nits interaction with a. number of different proteins , disc1 remains a. candidate gene for schizophrenia , and an understanding of its exact mechanistic role in neuronal pathways may shed more light on the disease .\nschizophrenia is a devastating neuropsychiatrie disorder , the genetics of which has been under extensive investigation for several decades . despite being an exceedingly complex disease in terms of both etiology and pathogenesis , recent research is finally shedding light on schizophrenia susceptibility genes .\nprominent , among them are the genes comt , dtnbp1 , grm3 , disc1 , nrg1 , akt1 , gad1 , rgs4 , and drd2 .\ndisc1 and its binding partners fez1 , nudel , and lis1 are involved in cytoplasmic dynein movement , neurofilament assembly , neuronal migration , and neurite morphology , and may play a role in the neurodevelopmental deficits observed in schizophrenia . although the precise neurobiological cause of schizophrenia continues to be unknown , the abundance of evidence regarding susceptibility genes for schizophrenia can not be dismissed .\nidentification of the molecular and cellular mechanisms that link susceptibility genes to the neurobiological functioning of the brain continues to be a major focus of research . as evidence for\nmay be determined that these genes operate in a convergent molecular pathway affecting neural development and synaptic plasticity .\nthe disruption of multiple genes within this pathway may lead to the development of schizophrenia .", "role": "user" }, { "content": "the disrupted in schizophrenia 1 ( disc1 ) gene has been identified as a schizophrenia susceptibility gene based on linkage and single nucleotide polymorphism ( snp ) association studies and clinical data , suggesting that risk snps impact on hippocampal structure and function . \n we hypothesized that altered expression of disc1 andlor its molecular partners ( nuclear distribution element - like [ nudel ] , fasciculation and elongation protein zeta-1 [ fez1 ] , and lissencephaly 1 [ l1s1 ] ) may underlie its pathogenic role in schizophrenia and explain its genetic association . \n we examined the expression of disc1 and its binding partners in the hippocampus and dorsolateral prefrontal cortex of postmortem human brains of schizophrenic patients and controls . \n we found no difference in the expression of disc1 mrna in schizophrenia , and no association with previously identified risk snps , however , the expression of nudel , fez1 , and lis1 vas significantly reduced in tissue from schizophrenic subjects , and the expression of each showed association with high - risk disc1 polymorphisms . \n these data suggest involvement of genetically linked abnormalities in the disc1 molecular pathway in the pathophysiology of schizophrenia .", "role": "assistant" } ]

[ { "content": "Craft a cohesive chapter for a literature review using the abstracts provided. Focus on the chapter's theme, weaving together insights and findings from the abstracts. Highlight key points and note any research gaps.\nLiterature Review Title: A survey of single and multi-hop link schedulers for mmWave wireless systems \nChapter Title: HYBRID APPROACHES \n1. Abstract of Cited Paper (BIB001): In this paper, we propose a spacial time slot scheduling algorithm for relay operation to improve the throughput performance of millimeter-wave wireless personal area network (mmWave WPAN) systems which employ directional antenna. The upcoming mmWave WPAN is designed for high definition TV (HDTV) transmission, high speed wireless docking and gaming, etc. Based on the fact that the significant path loss of millimeter-wave environments provides good space isolation, we have proposed a coexistence mechanism by sharing time slots for relay with direct transmission to guarantee throughput for the above data-rate-greedy applications. This paper is an extension that addresses spacial time slot scheduling for relay operation taking the effect of directional antenna into consideration. We model the throughput maximization with scheduling as an integer optimization and solve it by transforming the problem to a max-weight matching problem of a bipartite graph. We propose a scheduling algorithm based on the Kuhn-Munkres algorithm which can be used to solve the max weight matching problem. Simulation results show that there is up to 25% throughput improvement achieved compared with random scheduling method. \n2. Abstract of Cited Paper (BIB002): Millimeter-wave (mmWave) communications is a promising enabling technology for high rate (Giga-bit) multimedia applications. However, because oxygen absorption peaks at 60 GHz, mmWave signal power degrades significantly over distance. Therefore, a traffic flow transmitting over multiple short hops is preferred to improve flow throughput. In this paper, we first design a hop selection metric for the piconet controller (PNC) to select appropriate relay hops for a traffic flow, aiming to improve the flow throughput and balance the traffic load across the network. We then propose a multi-hop concurrent transmission (MHCT) scheme to exploit the spatial capacity of the mmWave WPAN. Extensive simulations show that the proposed MHCT scheme can significantly improve the traffic flow throughput and network throughput.\n\nReview Chapter:", "role": "user" }, { "content": "To date, only three works have considered both spatial re-use and selecting the best relay paths concurrently. In BIB001 , Zhou et al. propose two algorithms, random fit deflect routing (RFDR) and best fit deflect routing (BFDR) to schedule shared time slots to enable concurrent transmissions between direct links and multihop paths. The authors argue that although multi-hop relaying is effective in solving link degradation and blockage problems, the actual throughput of the network is decreased due to the extra airtime introduced by relaying. In Figure 12b , we see that Link(1, 2) is replaced with a multi-hop path Link(1, 3) and Link(3, 2) via relay node 3. This replacement adds an extra airtime if links are scheduled in a TDMA-based manner. However, if two links can be scheduled in the same time slot, the extra airtime in Figure 12b can be removed. In Figure 12c , Link(3, 2) is scheduled to share the same time slots with Link(4, 5). To schedule multiple links in the same time slot, the CCI on each link needs to be measured before scheduling. In particular, the authors derive the concurrent transmission condition as follows: a link is scheduled to a time slot only if the CCI on every link in the same time slot is lower than a given threshold. The authors consider a network consisting of n pairs of DEVs. There are m pairs of DEVs requesting multi-hop operation from the AP, where 0 < m < n. The problem is to find relays for these m pairs of DEVs and to schedule their transmission in a manner that maximizes system throughput. , d d ) . RFDR repeats the procedure until all multi-hop requests are processed. On the other hand, BFDR checks every DEV to find the best relay. In particular, BFDR checks every time slot in order to locate one that causes the least CCI to links scheduled in a time slot. BFDR terminates when all m pairs are scheduled with a relay. In a subsequent work, Zhou et al. BIB002 present a Binary Integer Program (BIP) with an objective to maximize data rate for the same problem. As the problem is NP-hard, they reformulated the BIP as a maximum weight bipartite matching problem. The resulting problem is then solved using the well-known Kuhn-Munkres (Hungarian) algorithm. The third work, see BIB003 , presents a multi-hop concurrent transmission scheme that consists of a hop selection metric and a concurrent transmission scheme. The aim is to improve flow and network throughput. The problem is to find an optimal route such that the aggregated throughput is maximized and one that also load balances nodes. In addition, to explore spatial reuse efficiency, given a set of multi-hop routes, the problem is to schedule non-conflicting links on the routes to transmit simultaneously in a fair manner. To solve the multi-hop route selection problem, the authors use a weighted graph. The weight of an edge reflects both distance and traffic load; i.e., where d(i, j) is the link distance between node i and node j, F (j) is the traffic load on node j,D andF are the average link length and traffic load among all nodes respectively. The hop selection metric always selects the multi-hop route with the minimum aggregated link weights as computed by the Dijkstra algorithm. The hop selection method re-computes routes whenever the network topology changes or new flows are added. The authors then propose a concurrent transmission scheme that preferentially schedules links on a path in descending order of transmission loads. It also groups non-interfering links together, and assigns the group a time slot that is equal to the maximum scheduled time slot. It is possible that some links cannot be scheduled in the current superframe because there are insufficient time slots remaining in the transmission period. These links are removed from consideration and the corresponding flows are removed from the current schedule and are re-scheduled in the next superframe.", "role": "assistant" } ]

[ { "content": "Examine the provided abstract from a computer science paper. Your objective is to identify and extract relationships between entities. Present these relationships in a structured JSON format.\n\nInput Text:\n\nMultimodal interfaces require effective parsing and understanding of utterances whose content is distributed across multiple input modes. Johnston 1998 presents an approach in which strategies for multimodal integration are stated declaratively using a unification-based grammar that is used by a multidimensional chart parser to compose inputs. This approach is highly expressive and supports a broad class of interfaces, but offers only limited potential for mutual compensation among the input modes, is subject to significant concerns in terms of computational complexity, and complicates selection among alternative multimodal interpretations of the input. In this paper, we present an alternative approach in which multimodal parsing and understanding are achieved using a weighted finite-state device which takes speech and gesture streams as inputs and outputs their joint interpretation. This approach is significantly more efficient, enables tight-coupling of multimodal understanding with speech recognition, and provides a general probabilistic framework for multimodal ambiguity resolution.", "role": "user" }, { "content": "[[\"weighted finite-state device\", \"multimodal parsing and understanding\", \"USED-FOR\"], [\"approach\", \"multimodal parsing and understanding\", \"USED-FOR\"], [\"approach\", \"multimodal integration\", \"USED-FOR\"], [\"approach\", \"multimodal ambiguity resolution\", \"USED-FOR\"], [\"parsing\", \"Multimodal interfaces\", \"USED-FOR\"], [\"unification-based grammar\", \"multimodal integration\", \"USED-FOR\"], [\"speech and gesture streams\", \"weighted finite-state device\", \"USED-FOR\"], [\"speech recognition\", \"multimodal understanding\", \"CONJUNCTION\"], [\"unification-based grammar\", \"multidimensional chart parser\", \"USED-FOR\"]]", "role": "assistant" } ]

[ { "content": "Review the provided collection of medical RCT summaries. Your objective is to distill the essential insights into a brief conclusion. Focus solely on the synthesis of findings without additional commentary. The RCT summaries are as follows:\n\n\n\nReport Title 1:\nThe role of post-operative radiotherapy in non-small-cell lung cancer: a multicentre randomised trial in patients with pathologically staged T1-2, N1-2, M0 disease. Medical Research Council Lung Cancer Working Party.\nReport Abstract 1:\nThe role of post-operative radiotherapy for patients with non-small-cell lung cancer (NSCLC) is unclear despite five previous randomised trials. One deficiency with these trials was that they did not include adequate TNM staging, and so the present randomised trial was designed to compare surgery alone (S) with surgery plus post-operative radiotherapy (SR) in patients with pathologically staged T1-2, N1-2. M0 NSCLC. Between July 1986 and October 1993, 308 patients (154 S, 154 SR) were entered from 16 centres in the UK. The median age of the patients was 62 years, 74% were male, > 85% had normal or near normal levels of general condition, activity and breathlessness, 68% had squamous carcinoma, 52% had had a pneumonectomy, 63% had N1 disease and 37% N2 disease. SR patients received 40 Gy in 15 fractions starting 4-6 weeks post-operatively. Overall there was no advantage to either group in terms of survival, although definite local recurrence and bony metastases appeared less frequently and later in the SR group. In a subgroup analysis, in the N1 group no differences between the treatment groups were seen, but in the N2 group SR patients appeared to gain a one month survival advantage, delayed time to local recurrence and time to appearance of the bone metastases. There is, therefore, no clear indication for post-operative radiotherapy in N1 disease, but the question remains unresolved in N2 disease.\n\n\nReport Title 2:\nPostresection irradiation for T2 N0 M0 non-small cell carcinoma: a prospective, randomized study.\nReport Abstract 2:\nStage I nonirradiated T2 N0 non-small cell lung carcinoma has a postoperative prognosis not very different from stage II irradiated T1 N1 carcinoma. The hypothesis was that more locoregional malignant sites are overlooked in T2 N0 M0 than in T1 N0 M0 tumors, considering the better prognosis of this last group, and that T2 N0 cancer might benefit from postresection irradiation.\n From 1985 to 1991, 163 non-small cell lung carcinomas were classified T2 N0 M0 and randomized for irradiation or nonirradiation after operation. After revision of all the cases, 132 were included in this study: 60 were irradiated and 72 were not irradiated. All were followed up. The study was closed in October 1995. Statistical analysis was then performed considering volume, location, cell type, survival, and recurrence in the two groups.\n One hundred thirteen patients were followed up during a minimum of 5 years: the survival was 44.2%. There was no significant difference considering cell type or irradiation. There was no recurrence-free survivor beyond 5 years with a tumor invading the visceral pleura. At the close of the study (follow up, 4 years 3 months to 10 years 1 month), 49 of 132 patients were alive. The median survival was 3 years 11 months. Fifty-nine patients had died of local (21) or distant (40) recurrences (2 patients had both local and distant recurrence). There was again no significant difference considering cell type or irradiation, either in the survival or in the mode of recurrence.\n Stage I T2 N0 M0 non-small cell lung carcinoma tends to manifest distant metastasis. Prospective studies of stratified systemic adjuvant therapy should improve the present moderate result of radical resection in this group of tumors.\n\n\nReport Title 3:\nA study of postoperative radiotherapy in patients with non-small-cell lung cancer: a randomized trial.\nReport Abstract 3:\nTo study the value of postoperative radiotherapy for non-small-cell lung cancer (NSCLC) with positive regional lymph metastases (NI or N2) after radical surgery.\n From February 1982 to October 1995, 366 patients with NSCLC and N1 or N2 disease were randomized into postoperative radiotherapy (S + R) (183 patients) and no further treatment (S alone) (182 patients). Postoperative radiotherapy (RT) was administrated 3-4 weeks after radical operation. Irradiated fields covered the bronchial stump, ipsilateral hilum, and most of the mediastinum. The midplane dose was 6000 cGy/30 fractions/6 weeks, with the spinal cord limited to 4000 cGy/20 fractions/4 weeks or less. One hundred thirty-four patients in S + R group and 162 patients in S alone group were evaluated. Clinical data were comparable in both arms, except for the numbers of N2 patients.\n The 3-year and 5-year overall survival rates were 51.9% and 42.9% in the S + R group and 50.2% and 40.5% in the S alone Group (p = 0.56). The 3-year and 5-year disease-free survival rates were 50.7% +/- 4.7% and 42.9% +/- 5.2% in the S + R group vs. 44.4% +/- 4.3% and 38.2% +/- 4.5% in the S alone group (p = 0.28), respectively. In the patients with NI or T3-4 tumors, there was a trend toward improved survival in the S + R group, especially in the patients with T3-4N1M0. These patients demonstrated 20% improvement in overall survival (p = 0.092) and greater than 20% better disease-free survival (p = 0.057). Postoperative RT reduced local recurrence but had no impact on distant metastases.\n Postoperative RT significantly reduced local relapses, but did not improve overall survival, due to a high frequency of distant metastases in this patient group.\n\n\nReport Title 4:\nAdjuvant radiotherapy in non-small cell lung cancer with pathological stage I: definitive results of a phase III randomized trial.\nReport Abstract 4:\nTo evaluate the benefits and the drawbacks of post-operative radiotherapy in completely resected Stage I (a and b) non-small cell lung cancer (NSCLC).\n Patients with pathological Stages Ia and Ib NSCLC have been randomized into two groups: Group 1 (G1) received adjuvant radiotherapy, Group 0 (G0) the control group did not receive any adjuvant therapy. Local control, toxicity and survival have been evaluated.\n Between July 1989 and June 1997, 104 patients with pathological stage I NSCLC have been enrolled in this study. Fifty-one patients were randomized to G1 and 53 to G0. Six patients have been excluded from the study due to incomplete follow-up data. Regarding local control, one patient in the G1 group had a local recurrence (2.2%) while in the G0 12 local recurrences have been observed (23%). Seventy-one percent of patients are disease-free at 5 years in G1 and 60% in G0 (P=0.039). Overall 5-year survival (Kaplan-Meier) showed a positive trend in the treated group: 67 versus 58% (P=0.048). Regarding toxicity in G1, six patients experienced a grade 1 acute toxicity. Radiological evidence of long-term lung toxicity, with no significant impairment of the respiratory function, has been detected in 18 of the 19 patients who have been diagnosed as having a post-radiation lung fibrosis.\n Adjuvant radiotherapy gave good results in terms of local control in patients with completely resected NSCLC with pathological Stage I. Overall 5-year survival and disease-free survival showed a promising trend. Treatment-related toxicity is acceptable.\n\n\nReport Title 5:\nPostoperative radiotherapy for radically resected N2 non-small-cell lung cancer (NSCLC): randomised clinical study 1988-1992.\nReport Abstract 5:\nIn the period 1988-1992, 74 consecutive radically resected patients with NSCLC were randomised to postoperative radiotherapy or surgery alone in order to evaluate the influence of postoperative radiotherapy on survival. There were 61 males and 13 females, aged 35-80 years, median 59 years. Their distribution by stage was as follows: pT1N2 = 19, pT2N2 = 54, pT3N2 = one patient; histology: 32 squamous, 32 adeno and 10 large cell carcinomas; surgery: atypical resection in six, lobectomy in 27, bilobectomy in ten, and pneumonectomy in 31 patients. In 27 patients, only one lymph node in a single mediastinal lymph node site was affected; in 31 patients more than one lymph node in one site; in 16 patients more sites were affected. In 35/74 patients radiotherapy of hilar and mediastinal sites with 3000 cGy in 2 weeks was performed. On December 31, 1994, 19 patients (26%) were still alive; 39/55 patients died of the following causes: locoregional failure-10(26%), distant metastases- 25 (64%), other tumor-unrelated causes-four patients (10%). Five-year survival rates did not show statistically significant differences between the irradiated and surgically treated patients only with respect to sex, pTNM stage, histology and frequency of locoregional failure. The number of metastatic mediastinal lymph nodes was the only significant prognostic factor (P < 0.005) in both randomised groups.", "role": "user" }, { "content": "PORT is detrimental to patients with early stage completely resected non-small cell lung cancer and should not be used in the routine treatment of such patients. The role of PORT in the treatment of N2 tumours is not clear and may justify further research.", "role": "assistant" } ]

[ { "content": "Write an abstract for the research paper below. Your response should only include the abstract and no additional text.\n\nArticle text:\ndispersion forces such as the casimir \npolder interaction between microscopic particles ( atoms and molecules ) with macroscopic bodies are prototypical forces that result from quantum vacuum fluctuations of a physical quantity , in this case the electromagnetic field @xcite .\ntheir magnitude depends sensitively on the geometry of the macroscopic body and the optical response of both particle and medium . in the simplest case of flat surfaces and isotropic optical response the casimir \npolder force is usually attractive and perpendicular to the surface .\nhowever , in more complex geometries this force can be modified to a large extent .\nfor example , surfaces with gratings can induce force components that are parallel to the ( spatially averaged ) interface .\nthis has been shown for casimir forces between corrugated surfaces @xcite as well as for casimir polder forces @xcite .\nmoreover , the sign of the dispersion force can be reversed .\na repulsive force with associated equilibrium , at least in the form of a saddle point , has been predicted for objects above a metal plate with a circular hole @xcite and near wedges @xcite .\napart from geometry , non - equilibrium situations such as resonant casimir polder interactions of excited atoms can provide transient repulsion @xcite . in this article\n, we will show how a strong anisotropic optical response of an atom can lead to a repulsive casimir \npolder force normal to a one - dimensional grating structure . from a theoretical point of view , to compute an electromagnetic dispersion force means to determine the scattering properties of a surface , typically in terms of reflection matrices that enter a mode expansion @xcite or , equivalently , a green s tensor construction @xcite .\nhere we use the dyadic green s tensor expansion in terms of rayleigh reflection coefficients to investigate the interaction of an anisotropic atom with a one - dimensional periodic surface .\nwe require the scattering green s tensor for source point @xmath0 and field point @xmath1 being situated in the vacuum half space above a nano - grating ( see fig .\n[ ris1 ] ) . above a one - dimensional rectangular grating.,width=377 ] the grating displays a periodic surface profile in the @xmath2-direction with period @xmath3 , and height @xmath4 while being translationally invariant in the @xmath5-direction . to construct the green s tensor\n, we employ a plane - wave basis which is adapted to the symmetry of the system .\nwave vectors for upward ( + ) and downward ( - ) moving waves are parametrised as .\ntheir @xmath2-components are decomposed according to into a continuous part that lies within the first brillouin zone and a discrete part comprised of integer multiples of the reciprocal lattice vector .\nthe @xmath5-component takes arbitrary continuous values while the @xmath6-component then follows from the dispersion relation : @xmath7 for each such wave vector , we choose two perpendicular polarisation vectors @xmath8 and @xmath9 such that only the respective electric and magnetic fields exhibit non - vanishing @xmath6-components , respectively : @xmath10 these vectors are obviously normalised , and orthogonal to each other , , as well as to the unit wave vector , .\nthe three orthonormal vectors form a right - handed triad , . with these preparations at hand ,\nthe required scattering green s tensor can be given as @xmath11}}{k_y^n}\\ , { \\bm{e}}_{m+}^\\sigma r_{mn}^{\\sigma\\sigma'}{\\bm{e}}_{n-}^{\\sigma'}.\\end{gathered}\\ ] ] the rayleigh reflection coefficients conserve @xmath12 and @xmath13 of the incident wave , but they mix polarisations @xmath14 as well as diffraction orders @xmath15 @xcite . in general , they have to be calculated numerically by integrating the maxwell equations within the grating ( ) and imposing conditions of continuity at its upper and lower boundaries @xcite . for a rectangular grating ( fig . [ ris1 ] ) , the formalism for computing the rayleigh coefficients is presented in [ appa ] . before we proceed ,\nlet us derive some symmetry properties of the reflection coefficients as well as consider the asymptotes of small and large grating periods .\n_ schwarz reflection principle . _ like every causal response function , the scattering green s tensor obeys the schwarz reflection principle @xcite . applying this to eq . ( [ greentensor ] )\nleads to @xmath16 _ onsager reciprocity . _\nprovided that the grating consists of a medium which obeys time - reversal symmetry @xcite , the scattering green s tensor fulfils onsager reciprocity .\nthis implies @xmath17 _ grating symmetries .\n_ finally , we consider symmetries imposed by the geometry of the grating .\nthe invariance of the grating with respect to an inversion of the @xmath5 coordinate implies that the diagonal / off - diagonal rayleigh coefficients are even / odd functions of @xmath13 , respectively : @xmath18 for a symmetric grating with , we further have @xmath19 by virtue of the @xmath2-inversion symmetry .\nfurther symmetries can be obtained by combining the above .\nfor instance , eqs .\n( [ s1 ] ) and ( [ s2 ] ) imply for at purely imaginary frequencies .\nthe exponential factors @xmath20 and @xmath21 become either exponentially damped or rapidly oscillating whenever or , respectively . in the limit where the grating period is small with respect to the distances of source and field points from the grating , , this implies that the rayleigh sums in eq .\n( [ greentensor ] ) are effectively limited to small values . to leading order\n, we have @xmath22 in the coincidence limit .\nthis asymptote of the scattering green s tensor is thus translationally invariant along the @xmath2-direction and it is described by the effective properties of the grating averaged over one period .\nthe leading correction to this @xmath2-independent green s tensor is a harmonic variation in @xmath23 which is due to terms and . in particular for a symmetric grating ,\nthis correction is proportional to @xmath24 in the coincidence limit . in the opposite extreme of the grating period being very large with respect to the distances of source and field points from the grating , , very large rayleigh reflection orders contribute .\nwe thus have , , so that the polarisation unit vectors and reflection coefficients can be approximated by @xmath25 and .\ncarrying out the remaining @xmath12-integral , the scattering green s tensor assumes the asymptotic form @xmath26}{4\\pi^2(x - x ' ) } \\sum_{m , n=-\\infty}^\\infty{\\mathrm{e}}^{{\\mathrm{i}}q(mx - nx')}\\\\ \\times\\int_{-\\infty}^\\infty{\\mathrm{d}}k_z \\frac{{\\mathrm{e}}^{{\\mathrm{i}}(k_y^my+k_y^ny')+{\\mathrm{i}}k_z(z - z')}}{k_y^{n- } } \\sum_{\\sigma,\\sigma'=e , h}r_{mn}^{\\sigma\\sigma ' } { \\bm{e}}_{m+}^\\sigma { \\bm{e}}_{n-}^{\\sigma'}.\\end{gathered}\\ ] ] in the coincidence limit , the scattering green s tensor is then well described by a proximity force approximation @xcite where the grating is replaced by the local surface at .\nwithin leading - order perturbation theory , the cp potential of a ground - state atom within an arbitrary structure is given as @xcite @xmath27 , \\ ] ] where @xmath28 is the ground - state polarisability of the atom as given in terms of its transition frequencies and dipole matrix elements @xmath29 .\nusing the green s tensor ( [ greentensor ] ) from the previous section , we find the cp potential of an atom above a one - dimensional grating as @xmath30 with and @xmath31 in the limit of small grating period , we use the asymptote ( [ greentensorasymp1 ] ) of the green s tensor to find the @xmath2-independent potential @xmath32 for large grating period , eq .\n( [ greentensorasymp2 ] ) leads to @xmath33 with @xmath34 taken in all expressions inside the integrand .\nwe study a ground - state rb atom above a rectangular au grating as shown in fig .\nthe grating consists of a periodic array of rectangular bars of height and width with separation , so that the grating period is .\nthe atom grating potential is derived by numerically integrating eq .\n( [ cpgrating ] ) with the rayleigh coefficients as given in [ appa ] .\n.,width=529 ] to study the effect of possible anisotropies on the potential , we separate the latter into contributions from where @xmath35 is the ground - state polarisability of the rb atom : @xmath36 .\nthe resulting potentials at are shown in fig .\nwe find that the component @xmath37 leads to a repulsive casimir polder potential in normal direction at separations .\nthis is the first demonstration of a repulsive casimir polder potential for a grating geometry .\nnm above an au grating as a function of lateral position .\nthick lines : exact numerical results from eq .\n( [ cpgrating ] ) .\nthin lines : asymptotes from eq .\n( [ cpasymp2]).,width=529 ] in many cases of interest , a full numerical calculation of the potential is neither desirable nor needed . for short atom - grating separations , the asymptotic expression ( [ cpasymp2 ] )\ngives reliable results . in fig .\n[ ris3 ] , we show a comparison of the full numerical calculation according to eq .\n( [ cpgrating ] ) ( thick lines ) with the short - distance asymptote ( [ cpasymp2 ] ) ( thin lines ) at a fixed atom - grating distance of\n. the obvious appearance of a non - sinusoidal lateral force across the grating implies in particular that the repulsive @xmath37 component at leads to an unstable , saddle - point equilibrium in accordance with the generalised earnshaw theorem @xcite .\none further notices that the short - distance ( or large grating ) approximation already provides very accurate results already at . at smaller separations of ,\nthe difference between exact and approximate potentials are within the thickness of the lines .\nwe have shown that it is possible to generate repulsive casimir polder forces above material gratings using anisotropic atoms .\nour calculation was based on the green s tensor expansion of the electromagnetic field which , using a rayleigh expansion , yields both a numerically exact result as well as analytically tractable asymptotes for small and large gratings .\nsurprisingly , the short - distance ( or large grating ) asymptote becomes already accurate at a distance of above a grating with a period .\nsyb was supported by the dfg ( grant bu 1803/3 - 1 ) and the freiburg institute for advanced studies .\nvnm was partially supported by grants of saint petersburg state university 11.38.237.2015 and 11.38.660.2013 .\nvnm thanks the participants of the 9th friedmann seminar for interesting discussions ; it is a pleasure to thank the organizers for an excellent seminar .\nin the following , we determine the rayleigh reflection coefficients for the rectangular grating depicted in fig .\n[ ris1 ] . to this end\n, we express the electromagnetic fields above and below the grating for incident waves of polarisation @xmath38 according to eqs .\n( [ polarisationvectore ] ) and ( [ polarisationvectorh ] ) as ( the factor @xmath39 is omitted for brevity ) @xmath40 for and @xmath41 for , respectively . for simplicity , we take throughout this appendix . in the region @xmath42 one\ncan write @xmath43 , analogous decompositions hold for the other components of the electromagnetic field .\nit is convenient to denote by @xmath44 $ ] the @xmath45-component vector with components .\nwe further introduce a diagonal @xmath46-matrix @xmath47 the maxwell equations in the region can then be written as @xcite @xmath48}{\\partial y}-{\\mathrm{i}}k_z[e_y ] = { \\mathrm{i}}\\omega[h_x],\\qquad & & \\frac{\\partial[h_z]}{\\partial y}-{\\mathrm{i}}k_z [ h_y ] = -{\\mathrm{i}}\\omega[d_x ] , \\label{1}\\\\ { \\mathrm{i}}k_z[e_x]-i\\lambda[e_z]={\\mathrm{i}}\\omega[h_y],\\qquad & & { \\mathrm{i}}k_z[h_x]-i\\lambda[h_z]=-{\\mathrm{i}}\\omega[d_y ] , \\label{2}\\\\ { \\mathrm{i}}\\lambda[e_y]-\\frac{\\partial[e_x]}{\\partial y } = { \\mathrm{i}}\\omega[h_z],\\qquad & & { \\mathrm{i}}\\lambda[h_y]-\\frac{[h_x]}{\\partial y } = -{\\mathrm{i}}\\omega [ d_z ] .\n\\label{3}\\end{aligned}\\ ] ] writing and using the results of ref .\n@xcite , one has for a rectangular grating : @xmath49 here , @xmath50 is a toeplitz matrix defined as @xmath51 where @xmath52 is a fourier coefficient of the periodic function @xmath53 : @xmath54 in order to solve the above system of equations , we proceed as follows\n. equation ( [ 2 ] ) implies , which can be substituted into equations ( [ 1 ] ) and ( [ 3 ] ) to eliminate @xmath55 $ ] . similarly , eq . ( [ 2 ] ) leads to , which can be substituted into equations ( [ 1 ] ) and ( [ 3 ] ) to eliminate @xmath56 $ ] . as a result ,\nthe maxwell equations in the region can be rewritten as @xmath57 \\\\ [ e_z ] \\\\ [ h_x ] \\\\ [ h_z ] \\end{pmatrix } = m \\begin{pmatrix } [ e_x ] \\\\ [ e_z ] \\\\ [ h_x ] \\\\ [ h_z ] \\end{pmatrix } , \\label{eq1}\\ ] ] where the matrix @xmath58 is defined as @xmath59 knowing the transmitted fields ( [ ezt ] ) and ( [ hzt ] ) at , one can determine the fields at by integrating eq .\n( [ eq1 ] ) from @xmath60 to @xmath61 . imposing the continuity conditions on all fourier components of @xmath62 , [ e_z ] , [ h_x ] , [ h_z]$ ] at @xmath63 ,\none then determines the rayleigh reflection and transmission coefficients .\nd. maystre ( ed . ) _ selected papers on diffraction gratings _ ( spie , bellingham , 1993 ) ; r. petit ( ed . ) , _ electromagnetic theory of gratings _ ( springer - verlag , berlin , 1980 ) ; m. c. hutley , _ diffraction gratings _ ( academic press , london , 1982 ) ; e. g.loewen and e. popov , _ diffraction gratings and applications _ ( marcel dekker , new york , 1997 ) .", "role": "user" }, { "content": "we study the interaction of an atom with a one - dimensional nano - grating within the framework of macroscopic qed , with special emphasis on possible anisotropic contributions . to this end \n , we first derive the scattering green s tensor of the grating by means of a rayleigh expansion and discuss its symmetry properties and asymptotes . \n we then determine the casimir polder potential of an atom with the grating . \n in particular , we find that strong anisotropy can lead to a repulsive casimir polder potential in the normal direction . _ \n _ _ keywords _ : casimir polder potential ; material grating ; rayleigh scattering . \n pacs numbers : 34.35.+a , 37.10.vz , 42.50.nn , 42.25.gy", "role": "assistant" } ]

[ { "content": "Consider the following research inquiry and associated key terms. Review the dataset summaries provided and determine which datasets are suitable for addressing the research question. Base your decision on your understanding of machine learning datasets.\nProvide your answer as a JSON list. For example, for the inquiry \"Semi supervised image classification\", a possible response could be: [\"CIFAR-10\", \"CIFAR-100\"]. Ensure the response contains only the dataset names in JSON format.\n\nResearch Inquiry: A triplet-center loss based part-aware model for vehicle re-identification.\n\nKey Terms: vehicle re-identification video\n\nDataset Summaries:\nPartial-iLIDS: Partial iLIDS is a dataset for occluded person person re-identification. It contains a total of 476 images of 119 people captured by 4 non-overlapping cameras.\nVRAI: VRAI is a large-scale vehicle ReID dataset for UAV-based intelligent applications. The dataset consists of 137, 613 images of 13, 022 vehicle instances.\nVeRi-776: VeRi-776 is a vehicle re-identification dataset which contains 49,357 images of 776 vehicles from 20 cameras. The dataset is collected in the real traffic scenario, which is close to the setting of CityFlow.\nVehicleID: The “VehicleID” dataset contains CARS captured during the daytime by multiple real-world surveillance cameras distributed in a small city in China. There are 26,267 vehicles (221,763 images in total) in the entire dataset.\nPRID2011: PRID 2011 is a person reidentification dataset that provides multiple person trajectories recorded from two different static surveillance cameras, monitoring crosswalks and sidewalks. The dataset shows a clean background, and the people in the dataset are rarely occluded.\nMARS: MARS (Motion Analysis and Re-identification Set) is a large scale video based person reidentification dataset, an extension of the Market-1501 dataset. It has been collected from six near-synchronized cameras.\n\nDataset Options: A: Partial-iLIDS B: VRAI C: VeRi-776 D: VehicleID E: PRID2011 F: MARS", "role": "user" }, { "content": "[\"VeRi-776\", \"VehicleID\"]", "role": "assistant" } ]

[ { "content": "Explore the following research question and associated terms. Identify the most suitable dataset from the list provided. Use the dataset descriptions to guide your choice.\n\nInquiry: We propose a novel approach for learning novel visual concepts and their interactions with other concepts from a\n\nKeywords: novel visual concept learning images\n\nDataset Information:\nCOCO: The MS COCO (Microsoft Common Objects in Context) dataset is a large-scale object detection, segmentation, key-point detection, and captioning dataset. The dataset consists of 328K images.\nCommonsenseQA: The CommonsenseQA is a dataset for commonsense question answering task. The dataset consists of 12,247 questions with 5 choices each.\nFollowUp: 1000 query triples on 120 tables.\nWebVision: The WebVision dataset is designed to facilitate the research on learning visual representation from noisy web data. It is a large scale web images dataset that contains more than 2.4 million of images crawled from the Flickr website and Google Images search.\n\nAvailable Datasets: A: COCO B: CommonsenseQA C: FollowUp D: WebVision", "role": "user" }, { "content": "COCO", "role": "assistant" } ]

[ { "content": "Analyze the given text to identify specific entities. Focus on extracting relevant data.\n\nProvide your findings in JSON format. Each category should list the entities found.\n\nText:\n\nExploring the Energy Landscapes of Cyclic Tetrapeptides with Discrete Path Sampling. Cyclic tetrapeptides are an important class of biologically active molecules that exhibit interesting conformational dynamics, with slow interconversion of several different structures. We present calculations on their energy landscapes using discrete path sampling. In acyclic peptides and large cyclic peptides, isomers containing cis-peptide groups are much less stable than the all-trans isomers and separated from them by large barriers. Strain in small cyclic peptides causes the cis and trans isomers to be closer in energy and separated by much lower barriers. If d-amino acids or proline residues are introduced, isomers containing cis-peptides become more stable than the all-trans structures. We also show that changing the polarity of the solvent has a significant effect on the energy landscapes of cyclic tetrapeptides, causing changes in the orientations of the peptide groups and in the degree of intramolecular hydrogen bonding.", "role": "user" }, { "content": "{\"Chemical\": [\"Cyclic tetrapeptides\", \"cyclic tetrapeptides\", \"proline\", \"d-amino acids\", \"Cyclic Tetrapeptides\", \"hydrogen\"]}", "role": "assistant" } ]

[ { "content": "Examine the abstracts provided from a main scientific article and its cited works. Craft a narrative that synthesizes the key insights and contributions, emphasizing their interconnections. Employ numerical citations such as [1], [2], etc., to reference the cited works.\n\nMain Article Summary:\nWeakly supervised temporal action localization, which aims at temporally locating action instances in untrimmed videos using only video-level class labels during training, is an important yet challenging problem in video analysis. Many current methods adopt the \"localization by classification\" framework: first do video classification, then locate temporal area contributing to the results most. However, this framework fails to locate the entire action instances and gives little consideration to the local context. In this paper, we present a novel architecture called Cascaded Pyramid Mining Network (CPMN) to address these issues using two effective modules. First, to discover the entire temporal interval of specific action, we design a two-stage cascaded module with proposed Online Adversarial Erasing (OAE) mechanism, where new and complementary regions are mined through feeding the erased feature maps of discovered regions back to the system. Second, to exploit hierarchical contextual information in videos and reduce missing detections, we design a pyramid module which produces a scale-invariant attention map through combining the feature maps from different levels. Final, we aggregate the results of two modules to perform action localization via locating high score areas in temporal Class Activation Sequence (CAS). Extensive experiments conducted on THUMOS14 and ActivityNet-1.3 datasets demonstrate the effectiveness of our method.\n\nCited Works Summary:\n[1]: \n\n[2]: We propose a simple, yet effective approach for spatiotemporal feature learning using deep 3-dimensional convolutional networks (3D ConvNets) trained on a large scale supervised video dataset. Our findings are three-fold: 1) 3D ConvNets are more suitable for spatiotemporal feature learning compared to 2D ConvNets; 2) A homogeneous architecture with small 3x3x3 convolution kernels in all layers is among the best performing architectures for 3D ConvNets; and 3) Our learned features, namely C3D (Convolutional 3D), with a simple linear classifier outperform state-of-the-art methods on 4 different benchmarks and are comparable with current best methods on the other 2 benchmarks. In addition, the features are compact: achieving 52.8 accuracy on UCF101 dataset with only 10 dimensions and also very efficient to compute due to the fast inference of ConvNets. Finally, they are conceptually very simple and easy to train and use.\n\n[3]: \n\n[4]: Recently dense trajectories were shown to be an efficient video representation for action recognition and achieved state-of-the-art results on a variety of datasets. This paper improves their performance by taking into account camera motion to correct them. To estimate camera motion, we match feature points between frames using SURF descriptors and dense optical flow, which are shown to be complementary. These matches are, then, used to robustly estimate a homography with RANSAC. Human motion is in general different from camera motion and generates inconsistent matches. To improve the estimation, a human detector is employed to remove these matches. Given the estimated camera motion, we remove trajectories consistent with it. We also use this estimation to cancel out camera motion from the optical flow. This significantly improves motion-based descriptors, such as HOF and MBH. Experimental results on four challenging action datasets (i.e., Hollywood2, HMDB51, Olympic Sports and UCF50) significantly outperform the current state of the art.\n\n[5]: Deep convolutional networks have achieved great success for visual recognition in still images. However, for action recognition in videos, the advantage over traditional methods is not so evident. This paper aims to discover the principles to design effective ConvNet architectures for action recognition in videos and learn these models given limited training samples. Our first contribution is temporal segment network (TSN), a novel framework for video-based action recognition. which is based on the idea of long-range temporal structure modeling. It combines a sparse temporal sampling strategy and video-level supervision to enable efficient and effective learning using the whole action video. The other contribution is our study on a series of good practices in learning ConvNets on video data with the help of temporal segment network. Our approach obtains the state-the-of-art performance on the datasets of HMDB51 ( ( 69.4 , )) and UCF101 ( ( 94.2 , )). We also visualize the learned ConvNet models, which qualitatively demonstrates the effectiveness of temporal segment network and the proposed good practices (Models and code at https: github.com yjxiong temporal-segment-networks).\n\n[6]: Recent applications of Convolutional Neural Networks (ConvNets) for human action recognition in videos have proposed different solutions for incorporating the appearance and motion information. We study a number of ways of fusing ConvNet towers both spatially and temporally in order to best take advantage of this spatio-temporal information. We make the following findings: (i) that rather than fusing at the softmax layer, a spatial and temporal network can be fused at a convolution layer without loss of performance, but with a substantial saving in parameters, (ii) that it is better to fuse such networks spatially at the last convolutional layer than earlier, and that additionally fusing at the class prediction layer can boost accuracy, finally (iii) that pooling of abstract convolutional features over spatiotemporal neighbourhoods further boosts performance. Based on these studies we propose a new ConvNet architecture for spatiotemporal fusion of video snippets, and evaluate its performance on standard benchmarks where this architecture achieves state-of-the-art results.", "role": "user" }, { "content": "Action recognition. Action recognition has been widely studied in recent years, which aims to identify one or multiple action categories of a video. Earlier works mainly focus on hand-crafted feature engineering, such as improved Dense Trajectory (iDT) [1] [4] . With the development of convolutional neural networks, many deep learning based methods [3] [6] [5] [2] have been applied to action recognition task and achieve convincing performance. Two-stream network [3] [6] [5] typically consists of two branches which learn the appearance and motion information using RGB image and optical flow respectively. C3D network [2] simultaneously captures appearance and motion features using a series of 3D convolutional layers. These action recognition models are usually adopted to extract frame or unit level visual representation in long and untrimmed videos.", "role": "assistant" } ]

[ { "content": "Analyze the given paragraph from COVID-19 research. Determine the relevant topics discussed in the text. Your response should be a JSON array containing the identified topics. Ensure the output is a valid JSON array with no additional commentary.\n\nText:\n\nQingfei Paidu decoction (QFPD), a multi-component herbal formula, has been widely used to treat COVID-19 in China. However, its active compounds and mechanisms of action are still unknown. Firstly, we divided QFPD into five functional units (FUs) according to the compatibility theory of traditional Chinese medicine. The corresponding common targets of the five FUs were all significantly enriched in Go Ontology (oxidoreductase activity, lipid metabolic process, homeostatic process, etc.), KEGG pathways (steroid biosynthesis, PPAR signaling pathway, adipocytokine signaling pathway, etc.), TTD diseases (chronic inflammatory diseases, asthma, chronic obstructive pulmonary Disease, etc.), miRNA (MIR183), kinase (CDK7) and TF (LXR). QFPD contained 257 specific targets in addition to HCoV, pneumonia and ACE2 co-expression proteins. Then, network topology analysis of the five components-target-pathway-disease networks yielded 67 active ingredients. In addition, ADMET estimations showed that 20 compounds passed the stringent lead-like criteria and in silico drug-likeness test with high gastrointestinal absorption and the median lethal dose (LD50 > 1600 mg/kg). Moreover, 4 specific ingredients (M3, S1, X2 and O2) and 5 common ingredients (MS1, MX16, SX1, WO1 and XO1) of QFPD presented good molecular docking score for 2019-nCov structure and non-structure proteins. Finally, drug perturbation of COVID-19 network robustness showed that all five FUs may protect COVID-19 independently, and target 8 specifically expressed drug-attacked nodes which were related to the bacterial and viral responses, immune system, signaling transduction, etc. In conclusion, our new FUNP analysis showed that QFPD had a protection effect on COVID-19 by regulating a complex molecular network with safety and efficacy. Part of the mechanism was associated with the regulation of anti-viral, anti-inflammatory activity and metabolic programming.", "role": "user" }, { "content": "[\"Mechanism\", \"Treatment\"]", "role": "assistant" } ]

[ { "content": "Craft a cohesive chapter for a literature review using the abstracts provided. Focus on the chapter's theme, weaving together insights and findings from the abstracts. Highlight key points and note any research gaps.\nLiterature Review Title: Dataset search: a survey \nChapter Title: Data handling: extra knowledge \n1. Abstract of Cited Paper (BIB001): There are thousands of data repositories on the Web, providing access to millions of datasets. National and regional governments, scientific publishers and consortia, commercial data providers, and others publish data for fields ranging from social science to life science to high-energy physics to climate science and more. Access to this data is critical to facilitating reproducibility of research results, enabling scientists to build on others' work, and providing data journalists easier access to information and its provenance. In this paper, we discuss Google Dataset Search, a dataset-discovery tool that provides search capabilities over potentially all datasets published on the Web. The approach relies on an open ecosystem, where dataset owners and providers publish semantically enhanced metadata on their own sites. We then aggregate, normalize, and reconcile this metadata, providing a search engine that lets users find datasets in the “long tail” of the Web. In this paper, we discuss both social and technical challenges in building this type of tool, and the lessons that we learned from this experience.\n\nReview Chapter:", "role": "user" }, { "content": "In order to support the differentiated access and advanced exploratory interfaces articulated above, dataset search engines will need to become more advanced in their ingestion, indexing and cataloging procedures. This problem divides into two areas: incorporation of external knowledge in the data handling process and better management and usage of dataset-intrinsic information. As described in BIB002 , links between datasets are still rare, making identification and usage of extra knowledge difficult. Incorporating external knowledge, whether through the use of domain ontologies, external quality indicators or even unstructured information (i.e., papers) that describe the datasets, is a critical problem. A concrete example of this problem: many datasets are described through code books that are written in natural language. These datasets are nearly useless without integration of external information about the codebooks themselves. Utilizing dataset-intrinsic information, is necessary to more fully capture the richness of each dataset, and allow users to express a richer set of criteria during search. Within this space, there are open problems related to data preprocessing. How to do quality assessment on the fly? What kinds of indexes around quality need to be created? Moving beyond quality, in general, the automatic creation and maintenance of metadata that describes datasets is difficult. Users rely up on metadata to chose appropriate datasets. Open problems for metadata include: 1. identifying the metadata that is of highest value to users w.r.t. datasets; 2. tools to automatically create and maintain that metadata; 3. automatic annotation of dataset with metadata-linking them automatically to global ontologies. In addition to pre-processing, current dataset search systems primarily rely on information retrieval architectures (e.g., indexing into ElasticSearch) to index and perform queries. Here, lessons learned from database architectures could be applied. This is particularly the case as we have seen the importance of lessons learned from relational query engines being applied in the case of distributed data environments BIB001 . Thus, we think an important open problem is what the most effective architectures are for dataset search systems.", "role": "assistant" } ]

[ { "content": "Analyze the provided paragraph from a scientific document. Your goal is to identify and extract relevant entities.\n\nFormat your findings as a JSON object, where each key represents a category of entities, and the corresponding value is a list of entities identified in that category. If no entities are found for a category, return an empty list.\n\nFocus on precision and ensure that the output is strictly in JSON format.\n\nDocument:\n\nStatistical algorithms improve accuracy of gene fusion detection Gene fusions are known to play critical roles in tumor pathogenesis. Yet, sensitive and specific algorithms to detect gene fusions in cancer do not currently exist. In this paper, we present a new statistical algorithm, MACHETE (Mismatched Alignment CHimEra Tracking Engine), which achieves highly sensitive and specific detection of gene fusions from RNA-Seq data, including the highest Positive Predictive Value (PPV) compared to the current state-of-the-art, as assessed in simulated data. We show that the best performing published algorithms either find large numbers of fusions in negative control data or suffer from low sensitivity detecting known driving fusions in gold standard settings, such as EWSR1-FLI1. As proof of principle that MACHETE discovers novel gene fusions with high accuracy in vivo, we mined public data to discover and subsequently PCR validate novel gene fusions missed by other algorithms in the ovarian cancer cell line OVCAR3. These results highlight the gains in accuracy achieved by introducing statistical models into fusion detection, and pave the way for unbiased discovery of potentially driving and druggable gene fusions in primary tumors.", "role": "user" }, { "content": "{\"AnatomicalStructure\": [\"OVCAR3\", \"EWSR1-FLI1\", \"cell line\"], \"Bacterium\": [], \"BiologicFunction\": [\"ovarian cancer\", \"cancer\", \"pathogenesis\", \"primary tumors\", \"tumor\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [], \"BodySystem\": [], \"Chemical\": [], \"ClinicalAttribute\": [], \"Eukaryote\": [], \"Finding\": [\"detecting\", \"negative\", \"detection\", \"detect\"], \"Food\": [], \"HealthCareActivity\": [], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [\"algorithms\", \"MACHETE\", \"Mismatched Alignment CHimEra Tracking Engine)\", \"RNA-Seq data\", \"statistical models\", \"published\", \"statistical algorithm\", \"Statistical algorithms\"], \"MedicalDevice\": [], \"Organization\": [\"public\"], \"PopulationGroup\": [], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [\"fusion\", \"gene fusion\", \"Gene fusions\", \"PCR\", \"fusions\", \"gene fusions\", \"validate\"], \"SpatialConcept\": [\"in vivo\"], \"Virus\": []}", "role": "assistant" } ]

[ { "content": "Examine the following abstract and identify distinct entities. Focus on extracting entities related to participants, interventions, and outcomes.\n\nPresent your findings in a JSON format like: {\"Participant\": [\"example entity\", ...], \"Intervention\": [\"example entity\", ...], \"Outcome\": [\"example entity\", ...]}. If no entities are found for a category, use an empty list.\n\nAbstract Content:\n\nEffect of postmenopausal hormonal replacement therapy on mammographic density and parenchymal pattern . PURPOSE To measure changes and predictors of change in mammograms obtained in postmenopausal women undergoing continuous combined hormonal replacement therapy ( HRT ) . MATERIALS AND METHODS Mammograms of 41 postmenopausal women obtained before and 1 year after the initiation of HRT were evaluated blindly according to the quantitative density percentage method and the Wolfe classification system . RESULTS Mammographic densities increased compared with baseline values in 73 % of subjects ( mean increase , 6.7 % ; 95 % confidence interval , 2.5 % , 11.0 % ; P = .003 ) . A shift in Wolfe classification from lower to greater parenchymal density was noted in 24 % of subjects ( P = .016 ) . Multivariate analysis results indicated that the lower the tissue density percentage before treatment , the greater the increase in density percentage after treatment . CONCLUSION An increase in mammographic density was demonstrated in most subjects undergoing continuous combined HRT and was most pronounced in subjects with a lower baseline density percentage .", "role": "user" }, { "content": "{\"Intervention\": [\"hormonal replacement therapy ( HRT )\", \"HRT\", \"Mammograms\", \"postmenopausal hormonal replacement therapy\"], \"Outcome\": [\"tissue density percentage\", \"increase in density percentage\", \"Mammographic densities\", \"parenchymal pattern\", \"lower to greater parenchymal density\", \"mammographic density\"], \"Participant\": [\"41 postmenopausal women obtained before and 1 year after the initiation of HRT\", \"postmenopausal women undergoing continuous combined hormonal replacement therapy ( HRT ) .\"]}", "role": "assistant" } ]

[ { "content": "Consider the following research inquiry and associated key terms. Review the dataset summaries provided and determine which datasets are suitable for addressing the research question. Base your decision on your understanding of machine learning datasets.\nProvide your answer as a JSON list. For example, for the inquiry \"Semi supervised image classification\", a possible response could be: [\"CIFAR-10\", \"CIFAR-100\"]. Ensure the response contains only the dataset names in JSON format.\n\nResearch Inquiry: I want to train a generative model that can manipulate images based on poses.\n\nKey Terms: image synthesis images pose\n\nDataset Summaries:\nConvAI2: The ConvAI2 NeurIPS competition aimed at finding approaches to creating high-quality dialogue agents capable of meaningful open domain conversation. The ConvAI2 dataset for training models is based on the PERSONA-CHAT dataset.\nDeepFashion: DeepFashion is a dataset containing around 800K diverse fashion images with their rich annotations (46 categories, 1,000 descriptive attributes, bounding boxes and landmark information) ranging from well-posed product images to real-world-like consumer photos.\nMulti-Modal CelebA-HQ: Multi-Modal-CelebA-HQ is a large-scale face image dataset that has 30,000 high-resolution face images selected from the CelebA dataset by following CelebA-HQ. Each image has high-quality segmentation mask, sketch, descriptive text, and image with transparent background.\nRoboNet: An open database for sharing robotic experience, which provides an initial pool of 15 million video frames, from 7 different robot platforms, and study how it can be used to learn generalizable models for vision-based robotic manipulation.\nSNIPS: The SNIPS Natural Language Understanding benchmark is a dataset of over 16,000 crowdsourced queries distributed among 7 user intents of various complexity: SearchCreativeWork (e.g. Find me the I, Robot television show), GetWeather (e.g.\nMarket-1501: Market-1501 is a large-scale public benchmark dataset for person re-identification. It contains 1501 identities which are captured by six different cameras, and 32,668 pedestrian image bounding-boxes obtained using the Deformable Part Models pedestrian detector.\n\nDataset Options: A: ConvAI2 B: DeepFashion C: Multi-Modal CelebA-HQ D: RoboNet E: SNIPS F: Market-1501", "role": "user" }, { "content": "[\"DeepFashion\", \"Market-1501\"]", "role": "assistant" } ]

[ { "content": "Analyze the given paragraph from COVID-19 research. Determine the relevant topics discussed in the text. Your response should be a JSON array containing the identified topics. Ensure the output is a valid JSON array with no additional commentary.\n\nText:\n\nWith the COVID-19 pandemic and the ensuing barriers to the collection and transport of donor cells, it is often necessary to collect and cryopreserve grafts before initiation of transplantation conditioning. The effect on transplantation outcomes in nonmalignant disease is unknown. This analysis examined the effect of cryopreservation of related and unrelated donor grafts for transplantation for severe aplastic anemia in the United States during 2013 to 2019. Included are 52 recipients of cryopreserved grafts who were matched for age, donor type, and graft type to 194 recipients who received noncryopreserved grafts. Marginal Cox regression models were built to study the effect of cryopreservation and other risk factors associated with outcomes. We recorded higher 1-year rates of graft failure (hazard ratio [HR], 2.26; 95% confidence interval, 1.17 to 4.35; P = .01) and of 1-year overall mortality (HR, 3.13; 95% CI, 1.60 to 6.11; P = .0008) after transplantation of cryopreserved compared with noncryopreserved grafts, with adjustment for sex, performance score, comorbidity, cytomegalovirus serostatus, and ABO blood group match. The incidence of acute and chronic graft-versus-host disease did not differ between the 2 groups. Adjusted probabilities of 1-year survival were 73% (95% CI, 60% to 84%) in the cryopreserved graft group and 91% (95% CI, 86% to 94%) in the noncryopreserved graft group. These data support the use of noncryopreserved grafts whenever possible in patients with severe aplastic anemia.", "role": "user" }, { "content": "[\"Prevention\"]", "role": "assistant" } ]

[ { "content": "Analyze the following collection of medical RCT summaries. Your goal is to craft a concise synthesis of the findings. Focus on the core insights and present them succinctly. Only include the synthesis in your response. Below are the RCT summaries:\n\n\n\nReport 1:\nTitle: Low 25-OH vitamin D is associated with benign prostatic hyperplasia.\nSummary: PURPOSE We tested the hypothesis that low vitamin D is associated with benign prostatic hyperplasia . We also studied whether body composition , sex hormones , serum sex hormone-binding globulin , albumin corrected serum calcium , adiponectin and lipid status are associated with benign prostatic hyperplasia . MATERIAL S AND METHODS We investigated 184 representative , r and omly selected men 72 to 76 years old enrolled in the Gothenburg arm of the Osteoporotic Fractures in Men Study ( MrOS ) . Men with a history of prostate cancer , prostate operation or medication for benign prostatic hyperplasia were excluded from study , leaving 155 available for analysis . A cross-sectional study was performed in which benign prostatic hyperplasia measured by total prostate volume was related to clinical , anthropometric , endocrine and metabolic factors on univariate and multivariate analyses with regression models . RESULTS Median prostate volume was 40 ml . In multivariate models only 25-OH vitamin D , albumin corrected serum calcium , serum sex hormone-binding globulin and high density lipoprotein cholesterol were significantly and inversely associated with large prostate gl and s. CONCLUSIONS The current report adds 4 independent factors associated with benign prostatic hyperplasia , including low 25-OH vitamin D , serum calcium , sex hormone-binding globulin and high density lipoprotein cholesterol\n\n\nReport 2:\nTitle: Impact of obesity on urinary storage symptoms: results from the FINNO study.\nSummary: PURPOSE Urinary storage symptoms are the most common and most bothersome urinary symptoms . Many studies on the relation between body weight and urinary symptoms have focused on urinary incontinence in women . We evaluated the association of obesity with urinary storage symptoms in a population based study of men and women age 18 to 79 years old . MATERIAL S AND METHODS Question naires were mailed to 6,000 adults r and omly identified from the Finnish Population Register . Self-reported height and weight were used to calculate body mass index . Urinary frequency , nocturia , urgency , stress urinary incontinence and urgency urinary incontinence were assessed using vali date d instruments . Multivariate logistic regression analyses ( adjusted for age , comorbidity and medications , and sociodemographic , lifestyle and reproductive factors ) were performed to evaluate associations between body mass index and each symptom . RESULTS Of the 6,000 individuals approached 3,727 participated ( 62.4 % response , 53.7 % women ) . In men and women obesity was associated with nocturia ( adjusted OR 2.0 , 95 % CI 1.2 - 3.3 for men ; OR 2.4 , 95 % CI 1.5 - 3.8 for women ) but not with urgency ( adjusted OR 1.2 , 95 % CI 0.7 - 2.3 for men ; OR 1.2 , 95 % CI 0.7 - 2.1 for women ) . In men obesity was also associated with urinary frequency ( OR 2.0 , 95 % CI 1.0 - 3.9 ) , and in women it was associated with stress urinary incontinence ( OR 1.9 , 95 % CI 1.2 - 3.0 ) and urgency urinary incontinence ( OR 3.0 , 95 % CI 1.2 - 7.4 ) . However , the number of men with stress urinary incontinence or urgency urinary incontinence was insufficient for precise analyses . CONCLUSIONS This study extends previous research by providing symptom specific associations between obesity and urinary storage symptoms in a population based sample of men and women . Obesity impacts individual urinary storage symptoms differently and these associations may be influenced by gender\n\n\nReport 3:\nTitle: Obesity increases and physical activity decreases lower urinary tract symptom risk in older men: the Osteoporotic Fractures in Men study.\nSummary: BACKGROUND Two potential targets for preventing chronic lower urinary tract symptoms ( LUTS ) in older men are obesity and physical activity . OBJECTIVE To examine associations of adiposity and physical activity with incident LUTS in community-dwelling older men . DESIGN , SETTING , AND PARTICIPANTS The Osteoporotic Fractures in Men Study ( MrOS ) is a prospect i ve cohort of men ≥65 yr of age . MrOS participants without LUTS and a history of LUTS treatment at baseline were included in this analysis . MEASUREMENTS Adiposity was measured with body mass index ( BMI ) , physical activity with the Physical Activity Scale for the Elderly ( PASE ) and self-report of daily walking , and LUTS with the American Urological Association Symptom Index . RESULTS AND LIMITATIONS The mean age ( st and ard deviation [ SD ] ) of the 1695 participants was 72 ( 5 ) yr at baseline . At a mean ( SD ) follow-up of 4.6 ( 0.5 ) yr , 524 ( 31 % ) of men reported incident LUTS . In multivariate analyses , compared with men of normal weight at baseline ( BMI < 25 kg/m² ) , overweight ( BMI : 25.0 - 29.9 kg/m² ) and obese ( ≥30 kg/m² ) men were 29 % ( adjusted odds ratio [ OR(adj ) ] : 1.29 ; 95 % confidence interval [ CI ] , 1.00 - 1.68 ) and 41 % ( OR(adj ) : 1.41 ; 95 % CI , 1.03 - 1.93 ) more likely to develop LUTS , respectively . Men in the highest quartile of physical activity were 29 % ( OR(adj ) : 0.71 ; 95 % CI , 0.53 - 0.97 ) and those who walked daily 20 % ( OR(adj ) : 0.80 ; 95 % CI , 0.65 - 0.98 ) less likely than their sedentary peers to develop LUTS , adjusting for BMI . The homogeneous composition of MrOS potentially diminishes the external validity of these results . CONCLUSIONS In older men , obesity and higher physical activity are associated with increased and decreased risks of incident LUTS , respectively . Prevention of chronic urinary symptoms represents another potential health benefit of exercise in elderly men\n\n\nReport 4:\nTitle: BXL628, a novel vitamin D3 analog arrests prostate growth in patients with benign prostatic hyperplasia: a randomized clinical trial.\nSummary: OBJECTIVE To evaluate the effect of BXL628 , a vitamin D3 analog , on prostate volume in patients with benign prostatic hyperplasia ( BPH ) . METHODS We conducted a phase II , double blind , r and omized , placebo controlled , clinical study . Patients eligible were aged > or=50 years , had a diagnosis of BPH and a prostate volume > or=40 ml . Eligible patients were r and omized and given either BXL628 150 mcg daily or placebo for 12 weeks . All r and omized patients underwent at baseline and at the end of study pelvic MRI to measure prostatic volume , uroflowmetry ( Qmax ) , American Urological Association Symptom Index ( AUASI ) , serum PSA , testosterone , dihydrotestosterone and luteizing hormone . RESULTS A total of 119 patients were r and omized : 57 patients to BXL628 and 62 to placebo . The percentage change of prostate volume at 12 week was -2.90 in the BXL628 group vs. + 4.32 in the placebo group ( p-value<0.0001 ) . The estimated difference between treatments ( BXL628 minus placebo ) was -7.22 % ( 95 % confidence limit -9.27 to -5.18 ) . Considering Qmax , mean change vs. baseline was -0.30 in BXL628 vs. + 1.50 in the placebo group : this finding was not statistically significant . The mean change of the AUASI total score at final visit vs. baseline was -1.77 in the BXL628 group vs. -3.45 in the placebo group ( p = not significant ) . CONCLUSION BXL628 was able to arrest prostate growth within 12 weeks in men aged > or=50 years with prostatic volume > or=40 ml . Its unprecedented mechanism of action may offer a new opportunity for the treatment of BPH\n\n\nReport 5:\nTitle: Association between family history of benign prostatic hyperplasia and urinary symptoms: results of a population-based study.\nSummary: Baseline measurements for a population -based prospect i ve cohort study were used to assess the association between family history of enlarged prostate and urinary symptoms . Between December 1989 and March 1991 , a group of r and omly selected men aged 40 - 79 years from Olmsted County , Minnesota , was administered a previously vali date d question naire that included questions with wording close to that of the American Urological Association 's Symptom Index . A detailed family history of an enlarged prostate was obtained by personal interview , and peak urinary flow rates were measured for each participant . Of the 2,119 men , 440 ( 21 percent ) reported a family history of an enlarged prostate . The age-adjusted odds of having moderate or severe urinary symptoms were elevated among those with a family history relative to those without ( odds ratio = 1.3 , 95 percent confidence interval 1.1 - 1.7 ) . With simultaneous control for effects of age and worry about urologic function , the odds ratio remained at 1.3 ( 95 percent confidence interval 1.0 - 1.6 ) . Furthermore , this risk was greater for men with relatives diagnosed at a younger age ( odds ratio = 2.5 , 95 percent confidence interval 1.5 - 4.3 ) . Men with a family history were also 1.3 times as likely to have an impaired peak urinary flow rate . These findings suggest that men with a family history of an enlarged prostate may be at increased risk for development of symptoms and signs suggestive of benign prostatic hyperplasia and that this risk is greater in men with relatives diagnosed at a younger age . Recognition of this association may help to target early interventions and may lead to further clues about the causes of benign prostatic hyperplasia\n\n\nReport 6:\nTitle: The effect of benign lower urinary tract symptoms on subsequent prostate cancer testing and diagnosis.\nSummary: BACKGROUND Lower urinary tract symptoms ( LUTS ) are common and have been associated with the subsequent diagnosis of prostate cancer ( PCa ) in population cohorts . OBJECTIVE To determine whether the association between LUTS and PCa is due to the intensity of PCa testing after LUTS diagnosis . DESIGN , SETTING , AND PARTICIPANTS We prospect ively followed a representative , population -based cohort of 1922 men , aged 40 - 79 yr , from 1990 until 2010 with interviews , question naires , and abstract ing of medical records for prostate outcomes . Men were excluded if they had a previous prostate biopsy or PCa diagnosis . Self-reported LUTS was defined as an American Urological Association symptom index score > 7 ( n=621 ) . Men treated for LUTS ( n=168 ) were identified from review of medical records and /or self report . Median follow-up was 11.8 yr ( interquartile range : 10.7 - 12.3 ) . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Associations between self-reported LUTS , or treatment for LUTS , and risk of subsequent prostate biopsy and PCa were estimated using Cox proportional hazard models . RESULTS AND LIMITATIONS Fifty-five percent of eligible men enrolled in the study . Men treated for LUTS were more likely to undergo a prostate biopsy ( hazard ratio [ HR ] : 2.4 ; 95 % confidence interval [ CI ] , 1.7 - 3.3 ) . Men younger than 65 yr who were treated for LUTS were more likely to be diagnosed with PCa ( HR : 2.3 , 95 % CI , 1.5 - 3.5 ) , while men aged > 65 yr were not ( HR : 0.89 , 95 % CI , 0.35 - 1.9 ) . Men with self-reported LUTS were not more likely to be biopsied or diagnosed with PCa . Neither definition of LUTS was associated with subsequent intermediate- to high-risk cancer . The study is limited by lack of histologic or prostate-specific antigen level data for the cohort . CONCLUSIONS These results indicate that a possible cause of the association between LUTS and PCa is increased diagnostic intensity among men whose LUTS come to the attention of physicians . Increased symptoms themselves were not associated with intensity of testing or diagnosis\n\n\nReport 7:\nTitle: Genetic sequence variants are associated with severity of lower urinary tract symptoms and prostate cancer susceptibility.\nSummary: PURPOSE While a clear heritable component underlies lower urinary tract symptoms and benign prostatic hyperplasia , few studies have identified specific genetic factors . In contrast , recent genome-wide association studies identified single nucleotide polymorphisms that increase prostate cancer risk . Some of these single nucleotide polymorphisms may also predispose to surgical intervention for benign prostatic hyperplasia . We determined whether these single nucleotide polymorphisms are also associated with lower urinary tract symptom severity and benign prostatic hyperplasia medication use . MATERIAL S AND METHODS The genotypes of 38 single nucleotide polymorphisms previously associated with prostate cancer risk were determined for 1,168 healthy white male volunteers . American Urological Association symptom index score and medication for benign prostatic hyperplasia were documented prospect ively . Statistical analyses were done to compare the frequency of the single nucleotide polymorphisms with American Urological Association symptom index and benign prostatic hyperplasia medication use . RESULTS Several single nucleotide polymorphisms , including rs2736098 on chromosome 5p15 , showed a significant relationship with benign prostatic hyperplasia medication . After adjusting for the other genetic variants , patient age and medication use , rs1571801 on chromosome 9q33.2 ( OR 1.31 , 95 % CI 1.0 - 1.74 ) and rs5945572 on chromosome Xp11 ( OR 1.28 , 95 % CI 1.04 - 1.59 ) were significantly associated with increased urinary symptoms . In contrast , rs445114 on chromosome 8q24 was marginally associated with decreased urinary symptoms ( OR 0.83 , 95 % CI 0.66 - 1.01 ) . CONCLUSIONS Of 38 single nucleotide polymorphisms that predispose to prostate cancer we identified 3 that are also associated with a well characterized lower urinary tract symptom phenotype . These single nucleotide polymorphisms may aid in the improved characterization of men with lower urinary tract symptoms/benign prostatic hyperplasia", "role": "user" }, { "content": "Few putative genetic risk variants have been reliably replicated across population s. We found consistent evidence of a reduced risk of LUTS associated with the common rs731236 variant of the vitamin D receptor gene in our meta-analyses .\nOnly one , a variant of the vitamin D receptor , was consistently protective across different population", "role": "assistant" } ]

[ { "content": "Analyze the following sentence to identify chemical entities of interest. List these entities in a JSON array format. If no entities are found, return an empty array.\n\nText to Analyze:\nThesim4algorithmusessplice-siteconsensussequencestorefinealignments.", "role": "user" }, { "content": "[]", "role": "assistant" } ]

[ { "content": "Review the provided sections from a computer science paper and distill the primary contribution into a single sentence. Provide only the summary sentence.\n\nSections:\n\nAchieving faster execution with shorter compilation time can foster further diversity and innovation in neural networks.\nHowever, the current paradigm of executing neural networks either relies on hand-optimized libraries, traditional compilation heuristics, or very recently genetic algorithms and other stochastic methods.\nThese methods suffer from frequent costly hardware measurements rendering them not only too time consuming but also suboptimal.\nAs such, we devise a solution that can learn to quickly adapt to a previously unseen design space for code optimization, both accelerating the search and improving the output performance.\nThis solution dubbed CHAMELEON leverages reinforcement learning whose solution takes fewer steps to converge, and develops an adaptive sampling algorithm that not only focuses on the costly samples (real hardware measurements) on representative points but also uses a domain knowledge inspired logic to improve the samples itself.\nExperimentation with real hardware shows that CHAMELEON provides 4.45×speed up in optimization time over AutoTVM, while also improving inference time of the modern deep networks by 5.6%.\nThe enormous computational intensity of DNNs have resulted in developing either hand-optimized kernels, such as NVIDIA cuDNN or Intel MKL that serve as backend for a variety of programming environment such as TensorFlow (Abadi et al., 2016) and PyTorch (Paszke et al., 2017) .\nHowever, the complexity of the tensor operations in DNNs and the volatility of algorithms, which has led to unprecedented rate of innovation (LeCun, 2019) , calls for developing automated compilation frameworks.\nTo imitate or even surpass the success of hand-optimized libraries, recent research has developed stochastic optimization passes for general code: STOKE (Schkufza et al., 2013) , and neural network code, TVM (Chen et al., 2018a) and TensorComprehensions (Vasilache et al., 2018) .\nTVM and TensorComprehensions are based on random or genetic algorithms to search the space of optimized code for neural networks.\nAutoTVM (Chen et al., 2018b ) builds on top of TVM and leverage boosted trees (Chen & Guestrin, 2016) as part of the search cost model to avoid measuring the fitness of each solution (optimized candidate neural network code), and instead predict its fitness.\nHowever, even with these innovations the optimizing compilation time can be around 10 hours for ResNet-18 (He et al., 2016) , and even more for deeper or wider networks.\nSince the general objective is to unleash new possibilities by developing automatic optimization passes, long compilation time hinders innovation and could put the current solutions in a position of questionable utility.\nTo solve this problem, we first question the very statistical guarantees which the aforementioned optimization passes rely on.\nThe current approaches are oblivious to the patterns in the design space of schedules that are available for exploitation, and causes inefficient search or even converges to solutions that may even be suboptimal.\nAlso, we notice that current approaches rely on greedy sampling that neglects the distribution of the candidate solutions (configurations).\nWhile greedy sampling that passively filter samples based on the fitness estimations from the cost models work, many of their hardware measurements (required for optimization) tend to be redundant and wasteful.\nMoreover, we found that current solutions that rely on greedy sampling lead to significant fractions of the candidate configurations being redundant over iterations, and that any optimizing compiler are prone to invalid configurations which significantly prolongs the optimization time.\nAs such, this work sets out to present an Adaptive approach to significantly reduce the compilation time and offer automation while avoiding dependence to hand-optimization, enabling far more diverse tensor operations in the next generation DNNs.\nWe tackle this challenge from two fronts with the following contributions:\n(1) Devising an Adaptive Exploration module that utilizes reinforcement learning to adapt to unseen design space of new networks to reduce search time yet achieve better performance.\n(2) Proposing an Adaptive Sampling algorithm that utilizes clustering to adaptively reduce the number of costly hardware measurements, and devising a domain-knowledge inspired Sample Synthesis to find configurations that would potentially yield better performance.\nReal hardware experimentation with modern DNNs (AlexNet, VGG-16, and ResNet-18) on a highend GPU (Titan Xp), shows that the combination of these two innovations, dubbed CHAMELEON, yields 4.45×speedup over the leading framework, AutoTVM.\nCHAMELEON is anonymously available in https://github.com/anony-sub/chameleon, which will be made public.\nWe present CHAMELEON to allow optimizing compilers to adapt to unseen design spaces of code schedules to reduce the optimization time.\nThis paper is also an initial effort to bring Reinforcement Learning to the realm of optimizing compilers for neural networks, and we also develop an Adaptive Sampling with domain-knowledge inspired Sample Synthesis to not only reduce the number of samples required to navigate the design space but also augment its quality in terms of fitness.\nExperimentation with real-world deep models shows that CHAMELEON not only reduces the time for compilation significantly, but also improves the quality of the code.\nThis encouraging result suggests a significant potential for various learning techniques to optimizing deep learning models.", "role": "user" }, { "content": "Reinforcement learning and Adaptive Sampling for Optimized Compilation of Deep Neural Networks.", "role": "assistant" } ]

[ { "content": "Examine the following abstract and identify distinct entities. Focus on extracting entities related to participants, interventions, and outcomes.\n\nPresent your findings in a JSON format like: {\"Participant\": [\"example entity\", ...], \"Intervention\": [\"example entity\", ...], \"Outcome\": [\"example entity\", ...]}. If no entities are found for a category, use an empty list.\n\nAbstract Content:\n\nIntramuscular compared to intravenous midazolam for paediatric sedation : A study on cardiopulmonary safety and effectiveness . BACKGROUND Sedation in children remains a controversial issue in emergency departments ( ED ) . Midazolam , as a benzodiazepine is widely used for procedural sedation among paediatrics . We compared the effectiveness and safety of two forms of midazolam prescription ; intramuscular ( IM ) and intravenous ( IV ) . PATIENTS AND METHODS A cohort study was conducted on two matched groups of 30 children referred to our ED between 2010 and 2011 . The first group received IM midazolam ( 0.3 mg/kg ) and the second group received IV midazolam ( 0.15 mg/kg ) for sedation . For evaluating effectiveness , sedation , irritation and cooperation score were followed every 15 min for 60 min and for safety assessment , vital signs and O 2 saturation were observed . RESULTS Mean age was 6.18 ± 2.88 years and 31 patients ( 51.7 % ) were male . All patients were sedated completely after using first dose . There was an overall complication rate of 68.3 % . 35 ( 58.3 % ) patients presented euphoria as the most common complication , but there was no statistical difference between the two groups ( P = 0.396 ) . Cases who received IV midazolam became sedated faster than those received IM midazolam ( P > 0.001 ) . The vital signs including heart rate , respiratory rate , systolic blood pressure and O 2 saturation changed significantly between and within groups during the sedation ( P < 0.05 ) . CONCLUSION Both forms of midazolam , IM and IV , are effective and safe for paediatric sedation in ED . Although the sedative with IV form might appear sooner , IM form of midazolam can be effectively used in patient with limited IV access . Patients are better to observe closely for psychological side-effects .", "role": "user" }, { "content": "{\"Intervention\": [\"IV midazolam\", \"IM midazolam\", \"Intramuscular compared to intravenous midazolam\", \"benzodiazepine\", \"midazolam prescription ; intramuscular ( IM ) and intravenous ( IV ) .\", \"Midazolam\"], \"Outcome\": [\"were sedated\", \"sedation\", \"irritation and cooperation score\", \"including heart rate , respiratory rate , systolic blood pressure and O 2 saturation\", \"are effective and safe\", \"an overall complication rate\", \"presented euphoria\", \"became sedated\", \"safety assessment , vital signs and O 2 saturation\", \"effectiveness\"], \"Participant\": [\"ED between 2010 and 2011\", \"31\", \"children\", \"Mean age was 6.18 \\u00b1 2.88 years\", \"male\", \"30\"]}", "role": "assistant" } ]

[ { "content": "Craft a cohesive chapter for a literature review using the abstracts provided. Focus on the chapter's theme, weaving together insights and findings from the abstracts. Highlight key points and note any research gaps.\nLiterature Review Title: Word Embeddings: A Survey \nChapter Title: Log-linear Model, Hierarchical Softmax \n1. Abstract of Cited Paper (BIB001): The supremacy of n-gram models in statistical language modelling has recently been challenged by parametric models that use distributed representations to counteract the difficulties caused by data sparsity. We propose three new probabilistic language models that define the distribution of the next word in a sequence given several preceding words by using distributed representations of those words. We show how real-valued distributed representations for words can be learned at the same time as learning a large set of stochastic binary hidden features that are used to predict the distributed representation of the next word from previous distributed representations. Adding connections from the previous states of the binary hidden features improves performance as does adding direct connections between the real-valued distributed representations. One of our models significantly outperforms the very best n-gram models. \n2. Abstract of Cited Paper (BIB002): Neural probabilistic language models (NPLMs) have been shown to be competitive with and occasionally superior to the widely-used n-gram language models. The main drawback of NPLMs is their extremely long training and testing times. Morin and Bengio have proposed a hierarchical language model built around a binary tree of words, which was two orders of magnitude faster than the non-hierarchical model it was based on. However, it performed considerably worse than its non-hierarchical counterpart in spite of using a word tree created using expert knowledge. We introduce a fast hierarchical language model along with a simple feature-based algorithm for automatic construction of word trees from the data. We then show that the resulting models can outperform non-hierarchical neural models as well as the best n-gram models. \n3. Abstract of Cited Paper (BIB003): We describe a single convolutional neural network architecture that, given a sentence, outputs a host of language processing predictions: part-of-speech tags, chunks, named entity tags, semantic roles, semantically similar words and the likelihood that the sentence makes sense (grammatically and semantically) using a language model. The entire network is trained jointly on all these tasks using weight-sharing, an instance of multitask learning. All the tasks use labeled data except the language model which is learnt from unlabeled text and represents a novel form of semi-supervised learning for the shared tasks. We show how both multitask learning and semi-supervised learning improve the generalization of the shared tasks, resulting in state-of-the-art-performance. \n4. Abstract of Cited Paper (BIB004): We present a new estimation principle for parameterized statistical models. The idea is to perform nonlinear logistic regression to discriminate between the observed data and some artificially generated noise, using the model log-density function in the regression nonlinearity. We show that this leads to a consistent (convergent) estimator of the parameters, and analyze the asymptotic variance. In particular, the method is shown to directly work for unnormalized models, i.e. models where the density function does not integrate to one. The normalization constant can be estimated just like any other parameter. For a tractable ICA model, we compare the method with other estimation methods that can be used to learn unnormalized models, including score matching, contrastive divergence, and maximum-likelihood where the normalization constant is estimated with importance sampling. Simulations show that noise-contrastive estimation offers the best trade-off between computational and statistical efficiency. The method is then applied to the modeling of natural images: We show that the method can successfully estimate a large-scale two-layer model and a Markov random field. \n5. Abstract of Cited Paper (BIB005): The recently introduced continuous Skip-gram model is an efficient method for learning high-quality distributed vector representations that capture a large number of precise syntactic and semantic word relationships. In this paper we present several extensions that improve both the quality of the vectors and the training speed. By subsampling of the frequent words we obtain significant speedup and also learn more regular word representations. We also describe a simple alternative to the hierarchical softmax called negative sampling. ::: ::: An inherent limitation of word representations is their indifference to word order and their inability to represent idiomatic phrases. For example, the meanings of \"Canada\" and \"Air\" cannot be easily combined to obtain \"Air Canada\". Motivated by this example, we present a simple method for finding phrases in text, and show that learning good vector representations for millions of phrases is possible. \n6. Abstract of Cited Paper (BIB006): Continuous space language models have recently demonstrated outstanding results across a variety of tasks. In this paper, we examine the vector-space word representations that are implicitly learned by the input-layer weights. We find that these representations are surprisingly good at capturing syntactic and semantic regularities in language, and that each relationship is characterized by a relation-specific vector offset. This allows vector-oriented reasoning based on the offsets between words. For example, the male/female relationship is automatically learned, and with the induced vector representations, “King Man + Woman” results in a vector very close to “Queen.” We demonstrate that the word vectors capture syntactic regularities by means of syntactic analogy questions (provided with this paper), and are able to correctly answer almost 40% of the questions. We demonstrate that the word vectors capture semantic regularities by using the vector offset method to answer SemEval-2012 Task 2 questions. Remarkably, this method outperforms the best previous systems. \n7. Abstract of Cited Paper (BIB007): We propose two novel model architectures for computing continuous vector representations of words from very large data sets. The quality of these representations is measured in a word similarity task, and the results are compared to the previously best performing techniques based on different types of neural networks. We observe large improvements in accuracy at much lower computational cost, i.e. it takes less than a day to learn high quality word vectors from a 1.6 billion words data set. Furthermore, we show that these vectors provide state-of-the-art performance on our test set for measuring syntactic and semantic word similarities. \n8. Abstract of Cited Paper (BIB008): This paper explores a simple and efficient baseline for text classification. Our experiments show that our fast text classifier fastText is often on par with deep learning classifiers in terms of accuracy, and many orders of magnitude faster for training and evaluation. We can train fastText on more than one billion words in less than ten minutes using a standard multicore~CPU, and classify half a million sentences among~312K classes in less than a minute.\n\nReview Chapter:", "role": "user" }, { "content": "Trained on DistBelief, which is the precursor to TensorFlow ). Reports better results than SGNS. Embeddings are also reported to be good for composition (into sentence, document embeddings). partition function or normalization factor required by softmax output layers 5 , such as those in neural network language models (NNLMs). Using a concept called importance sampling ), they managed to bypass calculation of the costly normalization factor, estimating instead gradients in the neural net using an auxiliary distribution (e.g. old n-gram language models) and sampling random examples from the vocabulary. They report gains of a factor of 19 in training time, with respect to the previous model, with similar scores (as measured by perplexity). A little bit later, Morin and Bengio 6 (2005) have 5 Softmax output layers are used when you train neural networks that need to predict multiple outputs, in this case the probability of each word in the vocabulary being the next word, given the context. 6 To our knowledge, this is the first time the term word suggested yet another approach for speeding up training and testing times, using a Hierarchical Softmax layer. They realized that, if one arranged the output words in a hierarchical binary tree structure, one could use, as a proxy for calculating the full distribution for each word, the probability that, at each node leading to the word, the correct path is chosen. Since the height of a binary tree over a set V of words is |V |/ log(|V |), this could yield exponential speedup. In practice, gains were less pronounced, but they still managed gains of a factor of 3 for training times and 100 for testing times, w.r.t. the model using importance sampling. BIB002 were probably the first authors to suggest the Log-bilinear Model 7 (LBL), embedding was used in this context.which has been very influential in later works as well. Another article by BIB003 can be seen as an extension of the LBL BIB002 ) model, using a slightly modified version of the hierarchical softmax scheme proposed by BIB001 , yielding a socalled Hierarchical Log-bilinear Model (HLBL). Whereas BIB001 used a prebuilt word tree from WordNet, BIB003 learned such a tree specifically for the task at hand. In addition to other minor optimizations, they reports large gains over previous LBL models (200 times as fast) and conclude that using purpose-built word trees was key to such results. Somewhat parallel to the works just mentioned, BIB004 approached the problem from a slightly different angle; they were the first to design model with the specific intent of learning embeddings only. In previous models, embeddings were just treated as an interesting by product of the main task (usually language models). In addition to this, they also introduced two improvements worth mentioning: they used words' full contexts (before and after) to predict the centre word 8 . Perhaps most importantly, they introduced a more clever way of leveraging unlabelled data for producing good embeddings: instead of training a language model (which is not the objective here), they expanded the dataset with false or negative examples 9 and simply trained a model that could tell positive (actually occurring) from false examples. 10 Here we should mention two specific contributions by Mikolov et al. (2009; , which have been used in later models. In the first work, (Mikolov et al. (2009) ) a two-step method for bootstraping a NNLM was suggested, whereby a first model was trained using a single word as context. Then, the full model (with larger context) was trained, using as initial embeddings those found by the first step. In (Mikolov et al. (2010) ), the idea of using Recurrent Neural Networks (RNNs) to train lanpendix A for more information. 8 Previous models focused on building language models, so they just used the left context. 9 I.e. sequences of words with the actual centre word replaced by a random word from the vocabulary. 10 This has been BIB006 ) called negative sampling and speeds up training because one can avoid costly operations such as calculating cross-entropies and softmax terms. guage models is first suggested; the argument is that RNNs keep state in the hidden layers, helping the model remember arbitrarily long contexts, and one would not need to decide, beforehand, how many words to use as context in either side. In 2012 Mnih and Teh have suggested further efficiency gains to the training of NNLMs. By leveraging Noise-contrastive Estimation (NCE). 11 NCE BIB005 ) is a way of estimating probability distributions by means of binary decisions over true/false examples. 12 . This has enabled the authors to further reduce training times for NNLMs. In addition to faster training times, they also report better perplexity score w.r.t. previous neural language models. It could be said that, in 2013, with BIB007 BIB008 BIB006 ) the NLP community have again (the main other example being BIB004 ) had its attention drawn to word embeddings as a topic worthy of research in and of itself. These authors analyzed the embeddings obtained with the training of a recurrent neural network model (Mikolov et al. (2010) ) with an eye to finding possible syntactic regularities possibly encoded in the vectors. Perhaps surprisingly, event for the authors themselves, they did find not only syntactic but also semantic regularities in the data. Many common relationships such as male-female, singularplural, etc actually correspond to arithmetical operations one can perform on word vectors (see Figure 1 for an example). A little later, in 2013b and 2013c, Mikolov et al. have introduced two models for learning embeddings, namely the continuous bag-of-words (CBOW) and skip-gram (SG) models. Both of these models are log-linear models (as seen in previous works) and use the two-step procedure (Mikolov et al. (2009) ) for training. The main difference between CBOW and SG lies in the loss function used to update the model; while CBOW trains a model that aims to predict the centre word based upon its context, in SG the roles are reversed, and the centre word is, instead, used to predict each word appearing in its context. The first versions of CBOW and SG BIB008 ) use hierarchical softmax layers, while the variants 13 suggested in BIB006 use negative sampling instead. Furthermore, the variants introduced subsampling of frequent words, to reduce the amount of noise due to overly frequent words and accelerate training. These variants were shown to perform better, with faster training times. Among the most recent contributions to prediction-based models for word embeddings one can cite the two articles BIB009 and BIB009 ) usually cited as the sources of the FastText 14 toolkit, made available by Facebook, Inc. They have suggested an improvement over the skip-gram model from BIB006 , whereby one learns not word embeddings, but n-gram embeddings (which can be composed to form words). The rationale behind this decision lies in the fact that languages that rely heavily on morphology and compositional word-building (such as Turkish, Finnish and other highly inflexional languages) have some information encoded in the word parts themselves, which can be used to help generalize to unseen words. They report better results w.r.t. SGNS (skip-gram variant with negative sampling) BIB006 ), particularly in languages such as German, French and Spanish. A structured comparison of prediction-based models for building word embeddings can be seen on Table 1 .", "role": "assistant" } ]

[ { "content": "Analyze the given text to identify specific entities. Focus on extracting relevant data.\n\nProvide your findings in JSON format. Each category should list the entities found.\n\nText:\n\nStructure-activity relationships of glucosamine-derived glycerolipids: the role of the anomeric linkage, the cationic charge and the glycero moiety on the antitumor activity. The potent antitumor activity of 1-O-hexadecyl-2-O-methyl-3-O-(2'-amino-2'-deoxy-β-D-glucopyranosyl)-sn-glycerol (1) was previously shown to arise through an apoptosis-independent pathway. Here, a systematic structure-activity study in which the effects of the anomeric linkage, the cationic charge and the glycero moiety on the antitumor activity is described. Eight analogues of 1 were synthesized, and their antitumor activity against breast (JIMT1 and BT549), pancreas (MiaPaCa2) and prostate (DU145, PC3) cancer was determined. 1-O-Hexadecyl-2-O-methyl-3-O-(2'-amino-2'-deoxy-α-D-glucopyranosyl)-sn-glycerol (2) consistently displayed the most potent activity against all five cell lines with CC(50) values in the range of 6-10 μM. However, replacement of the O-glycosidic linkage by a thioglycosidic linkage or replacement of the amino group by an azide or guanidino group leads to a threefold or greater decrease in potency. The glycero moiety also contributes to the overall activity of 1 and 2 but its effects are of lesser importance. Investigation into the mode of action of this class of compounds revealed that, in agreement with previous findings, the cytotoxic effects arise through induction of large acid vacuoles.", "role": "user" }, { "content": "{\"Chemical\": [\"1-O-Hexadecyl-2-O-methyl-3-O-(2\\u0027-amino-2\\u0027-deoxy-\\u03b1-D-glucopyranosyl)-sn-glycerol\", \"O\", \"thioglycosidic\", \"guanidino\", \"amino\", \"azide\", \"glucosamine\", \"1-O-hexadecyl-2-O-methyl-3-O-(2\\u0027-amino-2\\u0027-deoxy-\\u03b2-D-glucopyranosyl)-sn-glycerol\", \"glycero\"]}", "role": "assistant" } ]

[ { "content": "Evaluate the given public health statement using the provided research abstract. Your goal is to determine the relationship between the claim and the abstract content.\n\n- \"decision\": Indicate whether the abstract \"SUPPORTS\", \"CONTRADICTS\", or provides \"INSUFFICIENT\" information regarding the claim.\n- \"justification\": List sentences from the abstract that back your decision. If the decision is \"INSUFFICIENT\", leave this list empty.\n\nStatement: COVID-19: Novel Coronavirus May Lead to A Cardiac Arrest or heart attack\n\nResearch Abstract:\nBACKGROUND: A novel coronavirus disease (COVID-19) in Wuhan has caused an outbreak and become a major public health issue in China and great concern from international community.\nMyocarditis and myocardial injury were suspected and may even be considered as one of the leading causes for death of COVID-19 patients.\nTherefore, we focused on the condition of the heart, and sought to provide firsthand evidence for whether myocarditis and myocardial injury were caused by COVID-19.\nMETHODS: We enrolled patients with confirmed diagnosis of COVID-19 retrospectively and collected heart-related clinical data, mainly including cardiac imaging findings, laboratory results and clinical outcomes.\nSerial tests of cardiac markers were traced for the analysis of potential myocardial injury/myocarditis.\nRESULTS: 112 COVID-19 patients were enrolled in our study.\nThere was evidence of myocardial injury in COVID-19 patients and 14 (12.5%) patients had presented abnormalities similar to myocarditis.\nMost of patients had normal levels of troponin at admission, that in 42 (37.5%) patients increased during hospitalization, especially in those that died.\nTroponin levels were significantly increased in the week preceding the death.\n15 (13.4%) patients have presented signs of pulmonary hypertension.\nTypical signs of myocarditis were absent on echocardiography and electrocardiogram.\nCONCLUSIONS: The clinical evidence in our study suggested that myocardial injury is more likely related to systemic consequences rather than direct damage by the 2019 novel coronavirus.\nThe elevation in cardiac markers was probably due to secondary and systemic consequences and can be considered as the warning sign for recent adverse clinical outcomes of the patients.", "role": "user" }, { "content": "{\"verdict\": \"CONTRADICT\", \"evidence\": [\"CONCLUSIONS: The clinical evidence in our study suggested that myocardial injury is more likely related to systemic consequences rather than direct damage by the 2019 novel coronavirus.\", \"The elevation in cardiac markers was probably due to secondary and systemic consequences and can be considered as the warning sign for recent adverse clinical outcomes of the patients.\"]}", "role": "assistant" } ]

[ { "content": "Analyze the given paragraph from COVID-19 research. Determine the relevant topics discussed in the text. Your response should be a JSON array containing the identified topics. Ensure the output is a valid JSON array with no additional commentary.\n\nText:\n\nIn December 2019, the novel coronavirus pneumonia (COVID-19) occurred in Wuhan, Hubei Province, China. The epidemic quickly broke out and spread throughout the country. Now it becomes a pandemic that affects the whole world. In this study, three models were used to fit and predict the epidemic situation in China: a modified SEIRD (Susceptible-Exposed-Infected-Recovered-Dead) dynamic model, a neural network method LSTM (Long Short-Term Memory), and a GWR (Geographically Weighted Regression) model reflecting spatial heterogeneity. Overall, all the three models performed well with great accuracy. The dynamic SEIRD prediction APE (absolute percent error) of China had been </= 1.0% since Mid-February. The LSTM model showed comparable accuracy. The GWR model took into account the influence of geographical differences, with R2 = 99.98% in fitting and 97.95% in prediction. Wilcoxon test showed that none of the three models outperformed the other two at the significance level of 0.05. The parametric analysis of the infectious rate and recovery rate demonstrated that China's national policies had effectively slowed down the spread of the epidemic. Furthermore, the models in this study provided a wide range of implications for other countries to predict the short-term and long-term trend of COVID-19, and to evaluate the intensity and effect of their interventions.", "role": "user" }, { "content": "[\"Epidemic Forecasting\", \"Prevention\"]", "role": "assistant" } ]

[ { "content": "Evaluate the given public health statement using the provided research abstract. Your goal is to determine the relationship between the claim and the abstract content.\n\n- \"decision\": Indicate whether the abstract \"SUPPORTS\", \"CONTRADICTS\", or provides \"INSUFFICIENT\" information regarding the claim.\n- \"justification\": List sentences from the abstract that back your decision. If the decision is \"INSUFFICIENT\", leave this list empty.\n\nStatement: Taking a hot bath will not prevent you from catching COVID-19.\n\nResearch Abstract:\nAirborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via air-conditioning systems poses a significant threat for the continued escalation of the current coronavirus disease (COVID-19) pandemic.\nConsidering that SARS-CoV-2 cannot tolerate temperatures above 70 °C, here we designed and fabricated efficient air disinfection systems based on heated nickel (Ni) foam to catch and kill SARS-CoV-2.\nVirus test results revealed that 99.8% of the aerosolized SARS-CoV-2 was caught and killed by a single pass through a Ni-foam-based filter when heated up to 200 °C.\nAdditionally, the same filter was also used to catch and kill 99.9% of Bacillus anthracis, an airborne spore.\nThis study paves the way for preventing transmission of SARS-CoV-2 and other highly infectious airborne agents in closed environments.\nOne Sentence Summary Heated Ni-foam filters are capable of effectively catching and killing airborne SARS-CoV-2 and Bacillus anthracis spores.", "role": "user" }, { "content": "{\"verdict\": \"NEI\", \"evidence\": []}", "role": "assistant" } ]

[ { "content": "Analyze the following collection of medical RCT summaries. Your goal is to craft a concise synthesis of the findings. Focus on the core insights and present them succinctly. Only include the synthesis in your response. Below are the RCT summaries:\n\n\n\nReport 1:\nTitle: Exercise Stress Test Amplifies Genotype-Phenotype Correlation in the LQT1 and LQT2 Forms of the Long-QT Syndrome\nSummary: Background —Experimental studies suggest that the interval between peak and end of T wave ( Tpe ) in transmural ECGs reflects transmural dispersion of repolarization ( TDR ) , which is amplified by & bgr;-adrenergic stimulation in the LQT1 model . In 82 patients with genetically identified long-QT syndrome ( LQTS ) and 33 control subjects , we examined T-wave morphology and various parameters for repolarization in 12-lead ECGs including corrected QT ( QTc ; QT/R-R1/2 ) and corrected Tpe ( Tpec ; Tpe/R-R1/2 ) before and during exercise stress tests . Methods and Results —Under baseline conditions , LQT1 ( n=51 ) showed 3 cardinal T-wave patterns ( broad-based , normal-appearing , late-onset ) and LQT2 ( n=31 ) 3 patterns ( broad-based , bifid with a small or large notch ) . The QTc and Tpec were 510±68 ms and 143±53 ms in LQT1 and 520±61 ms and 195±69 ms in LQT2 , respectively , which were both significantly larger than those in control subjects ( 402±36 ms and 99±36 ms ) . Both QTc and Tpec were significantly prolonged during exercise in LQT1 ( 599±54 ms and 215±46 ms ) with morphological change into a broad-based T-wave pattern . In contrast , exercise produced a prominent notch on the descending limb of the T wave , with no significant changes in the QTc and Tpec ( 502±82 ms and 163±86 ms : n=19 ) in LQT2 . Conclusions —Tpe interval increases during exercise in LQT1 but not in LQT2 , which may partially account for the finding that fatal cardiac events in LQT1 are more often associated with exercise\n\n\nReport 2:\nTitle: The prognostic value of the QT interval and QT interval dispersion in all-cause and cardiac mortality and morbidity in a population of Danish citizens.\nSummary: AIMS To evaluate the prognostic value of the QT interval and QT interval dispersion in total and in cardiovascular mortality , as well as in cardiac morbidity , in a general population . METHODS AND RESULTS The QT interval was measured in all leads from a st and ard 12-lead ECG in a r and om sample of 1658 women and 1797 men aged 30 - 60 years . QT interval dispersion was calculated from the maximal difference between QT intervals in any two leads . All cause mortality over 13 years , and cardiovascular mortality as well as cardiac morbidity over 11 years , were the main outcome parameters . Subjects with a prolonged QT interval ( 430 ms or more ) or prolonged QT interval dispersion ( 80 ms or more ) were at higher risk of cardiovascular death and cardiac morbidity than subjects whose QT interval was less than 360 ms , or whose QT interval dispersion was less than 30 ms . Cardiovascular death relative risk ratios , adjusted for age , gender , myocardial infa rct , angina pectoris , diabetes mellitus , arterial hypertension , smoking habits , serum cholesterol level , and heart rate were 2.9 for the QT interval ( 95 % confidence interval 1.1 - 7.8 ) and 4.4 for QT interval dispersion ( 95 % confidence interval 1.0 - 19 - 1 ) . Fatal and non-fatal cardiac morbidity relative risk ratios were similar , at 2.7 ( 95 % confidence interval 1.4 - 5.5 ) for the QT interval and 2.2 ( 95 % confidence interval 1.1 - 4.0 ) for QT interval dispersion . CONCLUSION Prolongation of the QT interval and QT interval dispersion independently affected the prognosis of cardiovascular mortality and cardiac fatal and non-fatal morbidity in a general population over 11 years", "role": "user" }, { "content": "This meta- analysis showed that Tpeak-Tend interval is significant higher in individuals who are at elevated risk of adverse events in congenital LQTS , offering incremental value for risk stratification", "role": "assistant" } ]

[ { "content": "Review the following segment from a research document in AI. Answer the subsequent query based solely on the provided information. Limit your response to the answer itself.\n\nResearch Segment: To evaluate Self-Instruct empirically, we run this framework on GPT3 Brown et al. (2020), which is a vanilla LM (§4).The iterative Self-Instruct process on this model leads to about 52k instructions, paired with about 82K instance inputs and target outputs.We observe that the resulting data provides a diverse range of creative tasks and over 50% of them have less than 0.3 ROUGE-L overlaps with the seed instructions (§4.2).On this resulting data, we build GPT3{}_{\\textsc{Self-Inst}} by fine-tuning GPT3 (i.e., the same model used for generating the instructional data).We evaluate GPT3{}_{\\textsc{Self-Inst}} in comparison to various other models on both typical NLP tasks included in Super-NaturalInstructions Wang et al. (2022), and a set of new instructions that are created for novel usage of instruction-following models (§5).The SuperNI results indicate thatGPT3{}_{\\textsc{Self-Inst}} outperforms GPT3 (the original model) by a large margin (+33.1%) and nearly matches the performance of \\text{InstructGPT}_{\\text{001}}. Moreover, our human evaluation on the newly-created instruction set shows that GPT3{}_{\\textsc{Self-Inst}} demonstrates a broad range of instruction following ability, outperforming models trained on other publicly available instruction datasets and leaving only a 5% gap behind \\text{InstructGPT}_{\\text{001}}. Additionally, to compare Self-Instruct training with other publicly available instruction tuning data, we further finetune GPT3 model with data from PromptSource and SuperNI, which are used to train the T0 and Tk-Instruct models. We call them T0 training and SuperNI training for short, respectively.To save the training budget, we sampled 50K instances (but covering all their instructions) for each dataset, which has a comparable size to the instruction data we generated. Based on the findings from Wang et al. (2022) and our early experiments, reducing the number of instances per task does not degrade the model’s generalization performance to unseen tasks. We make the following observations from the results in Table 3.Self-Instructboosts the instruction-following ability of GPT3 by a large margin. The vanilla GPT3 model basically cannot follow human instructions at all. Upon manual analysis, we find that it usually generates irrelevant and repetitive text, and does not know when to stop generation.Compared with other models that are not specifically trained for SuperNI, GPT3{}_{\\textsc{Self-Inst}} achieves better performance than T0 or the GPT3 finetuned on the T0 training set, which takes tremendous human labeling efforts. Notably, GPT3{}_{\\textsc{Self-Inst}} also nearly matches the performance of \\text{InstructGPT}_{\\text{001}}, which is trained with private user data and human-annotated labels. Models trained on SuperNI training set still achieve better performance on its evaluation set, which we attribute to the similar instruction style and formatting. However, we show that Self-Instruct still brings in additional gains when combined with the SuperNI training set, proving its value as complementary data. Figure 5 provides the performance of GPT3 model and its instruction-tuned counterparts on this newly written instruction set. As anticipated, the vanilla GPT3 language model is largely unable to respond to instructions, and all instruction-tuned models demonstrate comparatively higher performance,Nonetheless, GPT3{}_{\\textsc{Self-Inst}} (i.e., GPT3 model fine-tuned with Self-Instruct) outperforms those counterparts trained on T0 or SuperNI by a large margin, demonstrating the value of the generated data despite the noise.Compared with \\text{InstructGPT}_{\\text{001}} (c.f. footnote 1), GPT3{}_{\\textsc{Self-Inst}} is quite close in the performance—if we count acceptable response with minor imperfections (Rating-3) as valid, GPT3{}_{\\textsc{Self-Inst}} is only 5% behind \\text{InstructGPT}_{\\text{001}}. Lastly, our evaluation confirms the impressive instruction-following ability of \\text{InstructGPT}_{\\text{002}} & \\text{InstructGPT}_{\\text{003}} models. Although there are many factors behind this success, we conjecture that future work can largely benefit from improving the quality of our generated data by using human annotators or training a reward model to select better generations, similar to the algorithm used in Ouyang et al. (2022). We introduce Self-Instruct, a task-agnostic method to improve the instruction-following capabilities of language models via its own generation of instruction data (instruction, input, and output samples) and bootstrapping with it. Our method conducts instruction-tuning of the original model on the pruned subset of generated samples. On experimenting with vanilla GPT3, we observe a 33% absolute improvement over the original model on Super-NaturalInstructions. This performance is on par with \\text{InstructGPT}_{\\text{001}}, which is trained with private user data and expensive human annotations. Furthermore, we curate a set of expert-written instructions for novel tasks. Human evaluation on this set shows that tuning GPT3 with Self-Instruct outperforms using existing public instruction datasets by a large margin, leaving only a 5% absolute gap behind \\text{InstructGPT}_{\\text{001}}. We hope Self-Instruct can serve as the first step to align pretrained language models to follow human instructions, and future work can build on top of this data to improve instruction-following models.\n\nInquiry: Was the performance difference between Self-Instruct training and SuperNI training significant?", "role": "user" }, { "content": "While it does appear as though there is a measurable performance improvement from SuperNI to Self-Instruct, quantifying the impact and magnitude of that improvement is not straightforward. Evaluations with ROGUE-L scores find that the absolute difference between both these methods is not very high, though additional information and context may be needed to judge the meaning of the absolute difference between these numbers. The authors do claim that they outperform T0 or SuperNI by a large margin, which is strong evidence to suggest that the difference was indeed significant, but such claims must be taken with some grains of salt since authors are usually incentivized to show their models are the best.", "role": "assistant" } ]

[ { "content": "Examine the provided text and determine the interactions between chemical entities and genes. Focus on identifying any connections present.\n\nPresent your findings in a structured JSON format. Each relationship should be represented as an array entry. If no interactions are detected, return an empty array.\n\nText Content:\n\nSulindac sulfide inhibits epidermal growth factor-induced phosphorylation of extracellular-regulated kinase 1/2 and Bad in human colon cancer cells. Colorectal cancer is the second leading cause of cancer death in the United States. Nonsteroidal anti-inflammatory drugs including sulindac are promising chemopreventive agents for colorectal cancer. Sulindac and selective cyclooxygenase (COX) -2 inhibitors cause regression of colonic polyps in familial polyposis patients. Sulindac induces apoptotic cell death in cancer cells in vitro and in vivo. In tumor cells, activation of extracellular-regulated kinase (ERK) 1/2 results in phosphorylation of several ERK1/2 effectors, including the proapoptotic protein Bad. Phosphorylation of Ser112 by ERK1/2 inactivates Bad and protects the tumor cell from apoptosis. Sulindac metabolites and other nonsteroidal anti-inflammatory drugs selectively inhibit ERK1/2 phosphorylation in human colon cancer cells. In this study we show that epidermal growth factor (EGF) strongly induces phosphorylation of ERK1/2 and Bad in HT29 colon cancer cells. EGF-stimulated phosphorylation of ERK and Bad is blocked by pretreatment with U0126, a selective MAP kinase kinase (MKK) 1/2 inhibitor. Similarly, pretreatment with sulindac sulfide blocks the ability of EGF to induce ERK1/2 and Bad phosphorylation, but also down-regulates total Bad but not ERK1/2 protein levels. The ability of sulindac to block ERK1/2 signaling by the EGF receptor may account for at least part of its potent growth-inhibitory effects against cancer cells.", "role": "user" }, { "content": "[[\"Sulindac\", \"INHIBITOR\", \"cyclooxygenase (COX) -2\"], [\"Sulindac sulfide\", \"INHIBITOR\", \"Bad\"], [\"U0126\", \"INHIBITOR\", \"ERK\"], [\"sulindac sulfide\", \"REGULATOR\", \"ERK1/2\"], [\"sulindac sulfide\", \"INDIRECT-DOWNREGULATOR\", \"Bad\"], [\"U0126\", \"INHIBITOR\", \"MAP kinase kinase (MKK) 1/2\"], [\"sulindac sulfide\", \"INHIBITOR\", \"EGF\"], [\"sulindac sulfide\", \"INHIBITOR\", \"Bad\"], [\"sulindac\", \"INDIRECT-DOWNREGULATOR\", \"ERK1/2\"], [\"sulindac\", \"INHIBITOR\", \"EGF receptor\"], [\"Sulindac\", \"DOWNREGULATOR\", \"ERK1/2\"], [\"U0126\", \"INHIBITOR\", \"Bad\"], [\"Sulindac sulfide\", \"INDIRECT-REGULATOR\", \"extracellular-regulated kinase 1/2\"]]", "role": "assistant" } ]

[ { "content": "Evaluate the given public health statement using the provided research abstract. Your goal is to determine the relationship between the claim and the abstract content.\n\n- \"decision\": Indicate whether the abstract \"SUPPORTS\", \"CONTRADICTS\", or provides \"INSUFFICIENT\" information regarding the claim.\n- \"justification\": List sentences from the abstract that back your decision. If the decision is \"INSUFFICIENT\", leave this list empty.\n\nStatement: Ginger can treat a coronavirus infection\n\nResearch Abstract:\nThe severity of coronavirus disease 2019 (COVID-19) infection is quite variable and the manifestations varies from asymptomatic disease to severe acute respiratory infection.\nFever, dry cough, dyspnea, myalgia, fatigue, loss of appetite, olfactory and gustatory dysfunctions are the most prevalent general symptoms.\nDecreased immune system cells such as suppressed regulatory T cells, cytotoxic and helper T cells, natural killer cells, monocytes/macrophages and increased proinflammatory cytokines are the characteristic features.\nCompounds derived from Allium sativum (garlic) have the potential to decrease the expression of proinflammatory cytokines and to reverse the immunological abnormalities to more acceptable levels.\nAllium sativum is suggested as a beneficial preventive measure before being infected with SARS-CoV-2 virus.\nAllium sativum is a functional food well-known for its immunomodulatory, antimicrobial, antiinflammatory, antimutagenic, antitumor properties.\nIts antiviral efficiency was also demonstrated.\nSome constituents of this plant were found to be active against protozoan parasites.\nWithin this context, it appears to reverse most immune system dysfunctions observed in patients with COVID-19 infection.\nThe relations among immune system parameters, leptin, leptin receptor, adenosin mono phosphate-activated protein kinase, peroxisome proliferator activated receptor-gamma have also been interpreted.\nLeptin's role in boosting proinflammatory cytokines and in appetite decreasing suggest the possible beneficial effect of decreasing the concentration of this proinflammatory adipose tissue hormone in relieving some symptoms detected during COVID-19 infection.\nIn conclusion, Allium sativum may be an acceptable preventive measure against COVID-19 infection to boost immune system cells and to repress the production and secretion of proinflammatory cytokines as well as an adipose tissue derived hormone leptin having the proinflammatory nature.", "role": "user" }, { "content": "{\"verdict\": \"NEI\", \"evidence\": []}", "role": "assistant" } ]

[ { "content": "Analyze the following excerpt from a biomedical text. Identify the relevant information needed to respond to the inquiry. Provide only the necessary details in your answer.\n\nContext: We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters’ index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases. Text: In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters' index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases. A cluster of pneumonia of unknown origin was identified in Wuhan, China, in December 2019 [1] . On 12 January 2020, Chinese authorities shared the sequence of a novel coronavirus termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated from some clustered cases [2] . Since then, the disease caused by SARS-CoV-2 has been named coronavirus disease 2019 (COVID -19) . As at 21 February 2020, the virus had spread rapidly mostly within China but also to 28 other countries, including in the World Health Organization (WHO) European Region [3] [4] [5] . Here we describe the epidemiology of the first cases of COVID-19 in this region, excluding cases reported in the United Kingdom (UK), as at 21 February 2020. The study includes a comparison between cases detected among travellers from China and cases whose infection was acquired due to subsequent local transmission. On 27 January 2020, the European Centre for Disease Prevention and Control (ECDC) and the WHO Regional Office for Europe asked countries to complete a WHO standard COVID-19 case report form for all confirmed and probable cases according to WHO criteria [6] [7] [8] . The overall aim of surveillance at this time was to support the global strategy of containment of COVID-19 with rapid identification and follow-up of cases linked to affected countries in order to minimise onward transmission. The surveillance objectives were to: describe the key epidemiological and clinical characteristics of COVID-19 cases detected in Europe; inform country preparedness; and improve further case detection and management. Data collected included demographics, history of recent travel to affected areas, close contact with a probable or confirmed COVID-19 case, underlying conditions, signs and symptoms of disease at onset, type of specimens from which the virus was detected, and clinical outcome. The WHO case definition was adopted for surveillance: a confirmed case was a person with laboratory confirmation of SARS-CoV-2 infection (ECDC recommended two separate SARS-CoV-2 RT-PCR tests), irrespective of clinical signs and symptoms, whereas a probable case was a suspect case for whom testing for SARS-CoV-2 was inconclusive or positive using a pan-coronavirus assay [8] . By 31 January 2020, 47 laboratories in 31 countries, including 38 laboratories in 24 European Union and European Economic Area (EU/EEA) countries, had diagnostic capability for SARS-CoV-2 available (close to 60% of countries in the WHO European Region), with cross-border shipment arrangements in place for many of those lacking domestic testing capacity. The remaining six EU/EEA countries were expected to have diagnostic testing available by mid-February [9] . As at 09:00 on 21 February 2020, 47 confirmed cases of COVID-19 were reported in the WHO European Region and one of these cases had died [4] . Data on 38 of these cases (i.e. all except the nine reported in the UK) are included in this analysis. The first three cases detected were reported in France on 24 January 2020 and had onset of symptoms on 17, 19 and 23 January respectively [10] . The first death was reported on 15 February in France. As at 21 February, nine countries had reported cases ( Figure) : Belgium (1), Finland (1), France (12), Germany (16), Italy (3), Russia (2), Spain (2), Sweden (1) and the UK (9 -not included further). The place of infection (assessed at national level based on an incubation period presumed to be up to 14 days [11] , travel history and contact with probable or confirmed cases as per the case definition) was reported for 35 cases (missing for three cases), of whom 14 were infected in China (Hubei province: 10 cases; Shandong province: one case; province not reported for three cases). The remaining 21 cases were infected in Europe. Of these, 14 were linked to a cluster in Bavaria, Germany, and seven to a cluster in Haute-Savoie, France [12, 13] . Cases from the Bavarian cluster were reported from Germany and Spain, whereas cases from the Haute-Savoie cluster were reported from France All but two cases were hospitalised (35 of 37 where information on hospitalisation was reported), although it is likely that most were hospitalised to isolate the person rather than because of severe disease. The time from onset of symptoms to hospitalisation (and isolation) ranged between 0 and 10 days with a mean of 3.7 days (reported for 29 cases). The mean number of days to hospitalisation was 2.5 days for cases imported from China, but 4.6 days for those infected in Europe. This was mostly a result of delays in identifying the index cases of the two clusters in France and Germany. In the German cluster, for example, the first three cases detected locally were hospitalised in a mean of 5.7 days, whereas the following six took only a mean of 2 days to be hospitalised. Symptoms at the point of diagnosis were reported for 31 cases. Two cases were asymptomatic and remained so until tested negative. The asymptomatic cases were tested as part of screening following repatriation and during contact tracing respectively. Of the remaining 29, 20 reported fever, 14 reported cough and eight reported weakness. Additional symptoms reported included headaches (6 cases), sore throat (2), rhinorrhoea (2), shortness of breath (2), myalgia (1), diarrhoea (1) and nausea (1). Fever was reported as the sole symptom for nine cases. In 16 of 29 symptomatic cases, the symptoms at diagnosis were consistent with the case definition for acute respiratory infection [16] , although it is possible that cases presented additional symptoms after diagnosis and these were not reported. Data on pre-existing conditions were reported for seven cases; five had no pre-existing conditions while one was reported to be obese and one had pre-existing cardiac disease. No data on clinical signs e.g. dyspnea etc. were reported for any of the 38 cases. All hospitalised cases had a benign clinical evolution except four, two reported in Italy and two reported in France, all of whom developed viral pneumonia. All three cases who were aged 65 years or over were admitted to intensive care and required respiratory support and one French case died. The case who died was hospitalised for 21 days and required intensive care and mechanical ventilation for 19 days. The duration of hospitalisation was reported for 16 cases with a median of 13 days (range: 8-23 days). As at 21 February 2020, four cases were still hospitalised. All cases were confirmed according to specific assays targeting at least two separate genes (envelope (E) gene as a screening test and RNA-dependent RNA polymerase (RdRp) gene or nucleoprotein (N) gene for confirmation) [8, 17] . The specimen types tested were reported for 27 cases: 15 had positive nasopharyngeal swabs, nine had positive throat swabs, three cases had positive sputum, two had a positive nasal swab, one case had a positive nasopharyngeal aspirate and one a positive endotracheal aspirate. As at 09:00 on 21 February, few COVID-19 cases had been detected in Europe compared with Asia. However the situation is rapidly developing, with a large outbreak recently identified in northern Italy, with transmission in several municipalities and at least two deaths [18] . As at 5 March 2020, there are 4,250 cases including 113 deaths reported among 38 countries in the WHO European region [19] . In our analysis of early cases, we observed transmission in two broad contexts: sporadic cases among travellers from China (14 cases) and cases who acquired infection due to subsequent local transmission in Europe (21 cases). Our analysis shows that the time from symptom onset to hospitalisation/case isolation was about 3 days longer for locally acquired cases than for imported cases. People returning from affected areas are likely to have a low threshold to seek care and be tested when symptomatic, however delays in identifying the index cases of the two clusters in France and Germany meant that locally acquired cases took longer to be detected and isolated. Once the exposure is determined and contacts identified and quarantined (171 contacts in France and 200 in Germany for the clusters in Haute-Savoie and Bavaria, respectively), further cases are likely to be rapidly detected and isolated when they develop symptoms [15, 20] . In the German cluster, for example, the first three cases detected locally were hospitalised in a mean of 5.7 days, whereas the following six were hospitalised after a mean of 2 days. Locally acquired cases require significant resources for contact tracing and quarantine, and countries should be prepared to allocate considerable public health resources during the containment phase, should local clusters emerge in their population. In addition, prompt sharing of information on cases and contacts through international notification systems such as the International Health Regulations (IHR) mechanism and the European Commission's European Early Warning and Response System is essential to contain international spread of infection. All of the imported cases had a history of travel to China. This was consistent with the epidemiological situation in Asia, and supported the recommendation for testing of suspected cases with travel history to China and potentially other areas of presumed ongoing community transmission. The situation has evolved rapidly since then, however, and the number of countries reporting COVID-19 transmission increased rapidly, notably with a large outbreak in northern Italy with 3,089 cases reported as at 5 March [18, 19] . Testing of suspected cases based on geographical risk of importation needs to be complemented with additional approaches to ensure early detection of local circulation of COVID-19, including through testing of severe acute respiratory infections in hospitals irrespectively of travel history as recommended in the WHO case definition updated on 27 February 2020 [21] . The clinical presentation observed in the cases in Europe is that of an acute respiratory infection. However, of the 31 cases with information on symptoms, 20 cases presented with fever and nine cases presented only with fever and no other symptoms. These findings, which are consistent with other published case series, have prompted ECDC to include fever among several clinical signs or symptoms indicative for the suspected case definition. Three cases were aged 65 years or over. All required admission to intensive care and were tourists (imported cases). These findings could reflect the average older age of the tourist population compared with the local contacts exposed to infection in Europe and do not allow us to draw any conclusion on the proportion of severe cases that we could expect in the general population of Europe. Despite this, the finding of older individuals being at higher risk of a severe clinical course is consistent with the evidence from Chinese case series published so far although the majority of infections in China have been mild [22, 23] . This preliminary analysis is based on the first reported cases of COVID-19 cases in the WHO European Region. Given the small sample size, and limited completeness for some variables, all the results presented should be interpreted with caution. With increasing numbers of cases in Europe, data from surveillance and investigations in the region can build on the evidence from countries in Asia experiencing more widespread transmission particularly on disease spectrum and the proportion of infections with severe outcome [22] . Understanding the infection-severity is critical to help plan for the impact on the healthcare system and the wider population. Serological studies are vital to understand the proportion of cases who are asymptomatic. Hospital-based surveillance could help estimate the incidence of severe cases and identify risk factors for severity and death. Established hospital surveillance systems that are in place for influenza and other diseases in Europe may be expanded for this purpose. In addition, a number of countries in Europe are adapting and, in some cases, already using existing sentinel primary care based surveillance systems for influenza to detect community transmission of SARS-CoV-2. This approach will be used globally to help identify evidence of widespread community transmission and, should the virus spread and containment no longer be deemed feasible, to monitor intensity of disease transmission, trends and its geographical spread. Additional research is needed to complement surveillance data to build knowledge on the infectious period, modes of transmission, basic and effective reproduction numbers, and effectiveness of prevention and case management options also in settings outside of China. Such special studies are being conducted globally, including a cohort study on citizens repatriated from China to Europe, with the aim to extrapolate disease incidence and risk factors for infection in areas with community transmission. Countries together with ECDC and WHO, should use all opportunities to address these questions in a coordinated fashion at the European and global level. provided input to the outline, multiple versions of the manuscript and gave approval to the final draft.\n\nInquiry: What was the clinical evolution of the hospitalised cases?", "role": "user" }, { "content": "All hospitalised cases had a benign clinical evolution except four,", "role": "assistant" } ]

[ { "content": "Analyze the provided abstract from a materials science paper. Identify synthesis events and represent them in JSON format. Each event should be captured as an object with:\n\n- \"trigger\": The verb indicating the synthesis action, directly quoted from the text.\n- \"arguments\": A list of pairs, each containing the text of an argument and its type, both extracted from the abstract. The types are predefined: [\"Atmospheric_Material\", \"Recipe_Precursor\", \"Solvent_Material\", \"Participant_Material\", \"Recipe_Target\"].\n\nAbstract:\n10.1039/c7ta05788a\nExtremely low thermal conductivity and high thermoelectric performance in liquid-like Cu2Se1-xSx polymorphic materials\n\nPolycrystalline Cu2Se1-xSx (x = 0.2, 0.3, 0.5, and 0.7) samples were synthesized by a combination of melting and long-term high-temperature annealing. High purity raw elements, Cu (shot, 99.999%, Alfa Aesar), Se (shot, 99.999%, Alfa Aesar), and S (shots, 99.9999%, Alfa Aesar) were combined in their stoichiometric ratios and placed in boron nitride crucibles, which were then sealed in fused silica tubes under vacuum. The temperature of the tubes was slowly (100 K h-1) raised to 1423 K and maintained at that temperature for 12 h, and then cooled down to 1073 K in 24 h. After annealing at 1073 K for 8 days, the tubes were furnace cooled to room temperature. Small single crystals were extracted from the polycrystalline ingot sample after the annealing process. Finally, the annealed ingots were crushed into powders and consolidated by spark plasma sintering (Sumitomo SPS-2040) at 873 K under a pressure of 65 MPa for 5 minutes. Electrically insulating and thermally conducting BN layers were sprayed onto the carbon foils and the inner sides of the graphite die before the SPS process in order to prohibit DC pulsed currents going through the powders.", "role": "user" }, { "content": "[{\"arguments\": [[\"Cu2Se1-xSx\", \"Recipe_Target\"]], \"trigger\": \"synthesized\"}, {\"arguments\": [[\"Cu\", \"Recipe_Precursor\"], [\"S\", \"Recipe_Precursor\"], [\"Se\", \"Recipe_Precursor\"]], \"trigger\": \"combined\"}]", "role": "assistant" } ]

[ { "content": "Examine the following abstract and identify distinct entities. Focus on extracting entities related to participants, interventions, and outcomes.\n\nPresent your findings in a JSON format like: {\"Participant\": [\"example entity\", ...], \"Intervention\": [\"example entity\", ...], \"Outcome\": [\"example entity\", ...]}. If no entities are found for a category, use an empty list.\n\nAbstract Content:\n\nJust-in-time evidence-based e-mail \" reminders \" in home health care : impact on nurse practices . OBJECTIVE To test the effectiveness of two interventions designed to improve the adoption of evidence-based practices by home health nurses caring for heart failure ( HF ) patients . DATA SOURCES/STUDY SETTING Information on nurse practices was abstracted from the clinical records of patients admitted between June 2000 and November 2001 to the care of 354 study nurses at a large , urban , nonprofit home care agency . STUDY DESIGN The study employed a randomized design with nurses assigned to usual care or one of two intervention groups upon identification of an eligible patient . The basic intervention was a one-time e-mail reminder highlighting six HF-specific clinical recommendations . The augmented intervention consisted of the initial e-mail reminder supplemented by provider prompts , patient education material , and clinical nurse specialist outreach . DATA COLLECTION At each home health visit provided by a study nurse to an eligible HF patient during the 45-day follow-up period , a structured chart abstraction tool was used to collect information on whether the nurse provided the care practices highlighted in the e-mail reminder . PRINCIPAL FINDINGS Both the basic and the augmented interventions greatly increased the practice of evidence-based care , according to patient records , in the areas of patient assessment and instructions about HF disease management . While not all results were statistically significant at conventional levels , intervention effects were positive in virtually all cases and effect magnitudes frequently were large . CONCLUSIONS The results of this randomized trial strongly support the efficacy of just-in-time evidence-based reminders as a means of changing clinical practice among home health nurses who are geographically dispersed and spend much of their time in the field .", "role": "user" }, { "content": "{\"Intervention\": [\"one-time e-mail reminder highlighting six HF-specific clinical recommendations\", \"initial e-mail reminder supplemented by provider prompts , patient education material , and clinical nurse specialist outreach\"], \"Outcome\": [\"just-in-time evidence-based reminders\", \"effect magnitudes frequently\", \"practice of evidence-based care\", \"intervention effects\", \"efficacy\"], \"Participant\": [\"home health nurses\", \"impact on nurse practices .\"]}", "role": "assistant" } ]

[ { "content": "Consider the following research inquiry and associated key terms. Review the dataset summaries provided and determine which datasets are suitable for addressing the research question. Base your decision on your understanding of machine learning datasets.\nProvide your answer as a JSON list. For example, for the inquiry \"Semi supervised image classification\", a possible response could be: [\"CIFAR-10\", \"CIFAR-100\"]. Ensure the response contains only the dataset names in JSON format.\n\nResearch Inquiry: This paper reviews recent advances of deep learning architectures for processing unstructured Euclidean data.\n\nKey Terms: point cloud processing 3d clouds\n\nDataset Summaries:\nCOG: A configurable visual question and answer dataset (COG) to parallel experiments in humans and animals. COG is much simpler than the general problem of video analysis, yet it addresses many of the problems relating to visual and logical reasoning and memory -- problems that remain challenging for modern deep learning architectures.\nSUN3D: SUN3D contains a large-scale RGB-D video database, with 8 annotated sequences. Each frame has a semantic segmentation of the objects in the scene and information about the camera pose.\nCLOTH: The Cloze Test by Teachers (CLOTH) benchmark is a collection of nearly 100,000 4-way multiple-choice cloze-style questions from middle- and high school-level English language exams, where the answer fills a blank in a given text. Each question is labeled with a type of deep reasoning it involves, where the four possible types are grammar, short-term reasoning, matching/paraphrasing, and long-term reasoning, i.e., reasoning over multiple sentences\nShapeNet: ShapeNet is a large scale repository for 3D CAD models developed by researchers from Stanford University, Princeton University and the Toyota Technological Institute at Chicago, USA. The repository contains over 300M models with 220,000 classified into 3,135 classes arranged using WordNet hypernym-hyponym relationships.\nCholec80: Cholec80 is an endoscopic video dataset containing 80 videos of cholecystectomy surgeries performed by 13 surgeons. The videos are captured at 25 fps and downsampled to 1 fps for processing.\nSemantic3D: Semantic3D is a point cloud dataset of scanned outdoor scenes with over 3 billion points. It contains 15 training and 15 test scenes annotated with 8 class labels.\nScanNet: ScanNet is an instance-level indoor RGB-D dataset that includes both 2D and 3D data. It is a collection of labeled voxels rather than points or objects.\n\nDataset Options: A: COG B: SUN3D C: CLOTH D: ShapeNet E: Cholec80 F: Semantic3D G: ScanNet", "role": "user" }, { "content": "[\"SUN3D\", \"ShapeNet\", \"Semantic3D\", \"ScanNet\"]", "role": "assistant" } ]

[ { "content": "Review the provided collection of medical RCT summaries. Your objective is to distill the essential insights into a brief conclusion. Focus solely on the synthesis of findings without additional commentary. The RCT summaries are as follows:\n\n\n\nReport Title 1:\nPsychological aspects of the Canadian randomized controlled trial of human growth hormone and low-dose ethinyl oestradiol in children with Turner syndrome. The Canadian Growth Hormone Advisory Group.\nReport Abstract 1:\nPreliminary results are presented after 2 years of the Canadian long-term multicentre study on the impact of hormone therapy on the final height, sexual development and psychological status of girls with Turner syndrome. Girls entering the study were randomized either to be treated with recombinant human growth hormone or to act as controls. Both groups received oestrogen replacement therapy in the same dose and format at the age of 13 years. However, for the purposes of the psychological study at this time, children receiving oestrogen were excluded from analysis. Girls treated with GH for a period of 2 years showed a significant increase in growth rate, which declined with continued treatment, while the growth rate in the control group remained constant throughout. There was a correlation between the higher growth rate and the girls' perceptions of themselves as more intelligent, more attractive, having more friends, greater popularity and experiencing less teasing than the untreated group. Growth rate was not correlated with family or school functioning.\n\n\nReport Title 2:\nGrowth hormone and low dose estrogen in Turner syndrome: results of a United States multi-center trial to near-final height.\nReport Abstract 2:\nA cardinal clinical feature of Turner syndrome (TS) is linear growth failure resulting in extreme short stature: the median adult height of untreated women with TS is 143 cm, 20 cm (8 in.) below that of the general female population. In the largest multicenter, randomized, long-term, dose-response study conducted in the United States, 232 subjects with TS received either 0.27 or 0.36 mg/kg.wk of recombinant human GH with either low dose ethinyl E2 or oral placebo. The study was placebo-controlled for both GH and estrogen for the first 18 months and remained placebo-controlled for estrogen for its duration. The near-final height of the 99 subjects whose bone age was at least 14 yr was 148.7 +/- 6.1 cm after 5.5 +/- 1.8 yr of GH started at a mean age of 10.9 +/- 2.3 yr; this represents an average increase of 1.3 +/- 0.6 SD scores from baseline (TS standard). Height was greater than 152.4 cm (60 in.) in 29% of subjects compared with the expected 5% of untreated patients. Mean near-final heights of subjects who received the lower GH dose, with or without estrogen, were 145.1 +/- 5.4 and 149.9 +/- 6.0 cm, respectively; those who received the higher GH dose with or without estrogen achieved mean near-final heights of 149.1 +/- 6.0 and 150.4 +/- 6.0 cm, respectively. Factors that most impacted outcome were younger age, lower bone age/chronological age ratio, lower body weight, and greater height SD score at study entry. This study demonstrates significant GH-induced improvement in height SD score, with correction of height to within the normal channels for a significant number of patients, and provides evidence of a GH dose-response effect. These data also indicate that early administration of estrogen, even at relatively low doses, does not improve gain in near-final height in patients with TS.\n\n\nReport Title 3:\nAcceleration of growth in Turner syndrome patients treated with growth hormone: summary of three-year results.\nReport Abstract 3:\nIn 1983, a multicenter, collaborative, prospective study was begun to investigate the efficacy of human growth hormone (hGH), alone and in combination with oxandrolone, in girls with Turner syndrome. While subjects in the control group grew 3.8 cm/yr (-0.1 SD for untreated Turner patients), subjects receiving hGH alone grew 6.6, 5.4 and 4.6 cm/yr in years 1-3, respectively (+3.1, +2.0, +1.4 SD). Subjects in the combination therapy group grew 9.8, 7.4 and 6.1 cm/yr (+6.6, +4.3, +3.0 SD). Turner subjects in both treatment groups showed increased in Bayley-Pinneau predicted adult heights and in Turner projected adult heights.", "role": "user" }, { "content": "Recombinant human growth hormone (hGH) doses between 0.3 to 0.375 mg/kg/wk increase short-term growth in girls with Turner syndrome by approximately three (two) cm in the first (second) year of treatment. Treatment in one trial increased final height by approximately six cm over an untreated control group. Despite this increase, the final height of treated women was still outside the normal range. Additional trials of the effects of hGH carried out with control groups until final height is achieved would allow better informed decisions about whether the benefits of hGH treatment outweigh the requirement of treatment over several years at considerable cost.", "role": "assistant" } ]

[ { "content": "Examine the provided biomedical abstract. Identify and list entities based on the specified categories: [\"Brand\", \"Drug\", \"DrugGroup\", \"UnapprovedDrug\"].\n\nFormat your findings as a JSON object: {\"Brand\": [\"Aspirin\", ...], \"DrugGroup\": [\"Salicylate\", ...], \"Drug\": [\"Phenobarbital\", ...], \"UnapprovedDrug\": [\"Heroin\", ...]}. Each key represents an entity type, and the corresponding value is a list of entities. If no entities are found for a type, use an empty list [].\n\nFocus solely on producing the JSON object.\n\nSource Text:\n\nIsoflurane potentiates the muscle relaxant effect of all muscle relaxants, most notably nondepolarizing muscle relaxants, and MAC (minimum alveolar concentration) is reduced by concomitant administration of N 2O. See CLINICAL PHARMACOLOGY.", "role": "user" }, { "content": "{\"Brand\": [], \"Drug\": [\"Isoflurane\"], \"DrugGroup\": [\"muscle relaxants\", \"nondepolarizing muscle relaxants\"], \"UnapprovedDrug\": []}", "role": "assistant" } ]

[ { "content": "Analyze the following text to identify specific entities. Focus on the categories provided: [\"Chemical\", \"Protein\"].\n\nDeliver your findings as a JSON structure: {\"Chemical\": [\"ExampleChemical\", ...], \"Protein\": [\"ExampleProtein\", ...]}. Each key represents an entity type, and the associated list contains the entities found. \n\nEnsure the response is strictly the JSON format without any extra text.\n\nSource:\n\nDiclofenac inhibits proliferation and differentiation of neural stem cells.\nNonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in clinical situations as anti-inflammatory, analgesic and antipyretic drugs. However, it is still unknown whether NSAIDs have effects on the development of the central nervous system. In the present study, we investigated the effects of NSAIDs on neural stem cell (NSC) proliferation and differentiation into neurons. In contrast to aspirin, naproxen, indomethacin and ibuprofen, treatment with diclofenac (10 microM) for 2 days induced the death of NSCs in a concentration-dependent manner. Diclofenac also inhibited the proliferation of NSCs and their differentiation into neurons. Treatment with diclofenac resulted in nuclear condensation (a morphological change due to apoptosis of NSCs) 24hr after the treatment and activated caspase-3 after 6 hr, indicating that diclofenac may cause apoptosis of neuronal cells via activation of the caspase cascade. These results suggest that diclofenac may affect the development of the central nervous system.", "role": "user" }, { "content": "{\"Chemical\": [\"indomethacin\", \"aspirin\", \"naproxen\", \"Diclofenac\", \"ibuprofen\", \"diclofenac\"], \"Protein\": [\"caspase\", \"caspase-3\"]}", "role": "assistant" } ]

[ { "content": "Transform the provided sections of a biomedical research paper into a digestible summary for a general audience. Focus on simplifying complex ideas while retaining key scientific insights.\n\nResearch Title: Guanylate cyclase 1 relies on rhodopsin for intracellular stability and ciliary trafficking\nContent Overview:\nAbstract:\nSensory cilia are populated by a select group of signaling proteins that detect environmental stimuli. How these molecules are delivered to the sensory cilium and whether they rely on one another for specific transport remains poorly understood. Here, we investigated whether the visual pigment, rhodopsin, is critical for delivering other signaling proteins to the sensory cilium of photoreceptor cells, the outer segment. Rhodopsin is the most abundant outer segment protein and its proper transport is essential for formation of this organelle, suggesting that such a dependency might exist. Indeed, we demonstrated that guanylate cyclase-1, producing the cGMP second messenger in photoreceptors, requires rhodopsin for intracellular stability and outer segment delivery. We elucidated this dependency by showing that guanylate cyclase-1 is a novel rhodopsin-binding protein. These findings expand rhodopsin’s role in vision from being a visual pigment and major outer segment building block to directing trafficking of another key signaling protein.\nIntroduction:\nPhotoreceptor cells transform information entering the eye as photons into patterns of neuronal electrical activity. This transformation takes place in the sensory cilium organelle, the outer segment. Outer segments are built from a relatively small set of structural and signaling proteins, including components of the classical G protein-coupled receptor( GPCR) phototransduction cascade. Such a distinct functional and morphological specialization allow outer segments to serve as a nearly unmatched model system for studying general principles of GPCR signaling( Arshavsky et al., 2002) and, in more recent years, a model for ciliary trafficking( Garcia-Gonzalo and Reiter, 2012; Nemet et al., 2015; Pearring et al., 2013; Schou et al., 2015; Wang and Deretic, 2014). Despite our deep understanding of visual signal transduction, little is known about how the outer segment is populated by proteins performing this function. Indeed, nearly all mechanistic studies of outer segment protein trafficking have been devoted to rhodopsin( Nemet et al., 2015; Wang and Deretic, 2014), which is a GPCR visual pigment comprising the majority of the outer segment membrane protein mass( Palczewski, 2006). The mechanisms responsible for outer segment delivery of other transmembrane proteins remain essentially unknown. Some of them contain short outer segment targeting signals, which can be identified through site-specific mutagenesis( Deretic et al., 1998; Li et al., 1996; Pearring et al., 2014; Salinas et al., 2013; Sung et al., 1994; Tam et al., 2000; 2004). A documented exception is retinal guanylate cyclase 1( GC-1), whose exhaustive mutagenesis did not yield a distinct outer segment targeting motif( Karan et al., 2011). GC-1 is a critical component of the phototransduction machinery responsible for synthesizing the second messenger, cGMP( Wen et al., 2014). GC-1 is the only guanylate cyclase isoform expressed in the outer segments of cones and the predominant isoform in rods( Baehr et al., 2007; Yang et al., 1999). GC-1 knockout in mice is characterized by severe degeneration of cones and abnormal light-response recovery kinetics in rods( Yang et al., 1999). Furthermore, a very large number of GC-1 mutations found in human patients causes one of the most severe forms of early onset retinal dystrophy, called Leber’s congenital amaurosis( Boye, 2014; Kitiratschky et al., 2008). Many of these mutations are located outside the catalytic site of GC-1, which raises great interest in understanding the mechanisms of its intracellular processing and trafficking. In this study, we demonstrate that, rather than relying on its own targeting motif, GC-1 is transported to the outer segment in a complex with rhodopsin. We conducted a comprehensive screen of outer segment protein localization in rod photoreceptors of rhodopsin knockout( Rho-/-) mice and found that GC-1 was the only protein severely affected by this knockout. Next, we showed that this unique property of GC-1 is explained by its interaction with rhodopsin, which likely initiates in the biosynthetic membranes and supports both intracellular stability and outer segment delivery of this enzyme. These findings explain how GC-1 reaches its specific intracellular destination and also expand the role of rhodopsin in supporting normal vision by showing that it guides trafficking of another key phototransduction protein.\nDiscussion:\nThe findings reported in this study expand our understanding of how the photoreceptor’s sensory cilium is populated by its specific membrane proteins. We have found that rhodopsin serves as an interacting partner and a vehicle for ciliary delivery of a key phototransduction protein, GC-1. This previously unknown function adds to the well-established roles of rhodopsin as a GPCR visual pigment and a major building block of photoreceptor membranes. We further showed that GC-1 is unique in its reliance on rhodopsin, as the other nine proteins tested in this study were expressed in significant amounts and faithfully localized to rod outer segments in the absence of rhodopsin. Our data consolidate a number of previously published observations, including a major puzzle related to GC-1: the lack of a distinct ciliary targeting motif encoded in its sequence. The shortest recombinant fragment of GC-1 which localized specifically to the outer segment was found to be very large and contain both transmembrane and cytoplasmic domains( Karan et al., 2011). Our study shows that GC-1 delivery requires rhodopsin and, therefore, can rely on specific targeting information encoded in the rhodopsin molecule. Interestingly, we also found that this information can be replaced by an alternative ciliary targeting sequence from a GPCR not endogenous to photoreceptors. This suggests that the functions of binding/stabilization of GC-1 and ciliary targeting are performed by different parts of the rhodopsin molecule. Our findings also shed new light on the report that both rhodopsin and GC-1 utilize IFT for their ciliary trafficking and co-precipitate with IFT proteins( Bhowmick et al., 2009). The authors hypothesized that GC-1 plays a primary role in assembling cargo for the IFT particle bound for ciliary delivery. Our data suggest that it is rhodopsin that drives this complex, at least in photoreceptor cells where these proteins are specifically expressed. Unlike GC-1’s reliance on rhodopsin for its intracellular stability or outer segment trafficking, rhodopsin does not require GC-1 as its expression level and localization remain normal in rods of GC-1 knockout mice( Baehr et al., 2007; and this study). The outer segment trafficking of cone opsins is not affected by the lack of GC-1 either( Baehr et al., 2007; Karan et al., 2008), although GC-1 knockout cones undergo rapid degeneration, likely because they do not express GC-2 – an enzyme with redundant function. The primary role of rhodopsin in guiding GC-1 to the outer segment is further consistent with rhodopsin directly interacting with IFT20, a mobile component of the IFT complex responsible for recruiting IFT cargo at the Golgi network( Crouse et al., 2014; Keady et al., 2011). It was also reported that GC-1 trafficking requires participation of chaperone proteins, most importantly DnaJB6( Bhowmick et al., 2009). Our data suggest that GC-1 interaction with DnaJB6 is transient, most likely in route to the outer segment, since we were not able to co-precipitate DnaJB6 with GC-1 from whole retina lysates( Figure 5). In contrast, the majority of GC-1 co-precipitates with rhodopsin from these same lysates, suggesting that these proteins remain in a complex after being delivered to the outer segment. Although our data do not exclude that the mature GC-1-rhodopsin complex may contain additional protein component( s), our attempts to identify such components by mass spectrometry have not yielded potential candidates. Interestingly, GC-1 was previously shown to stably express in cell culture where it localizes to either ciliary or intracellular membranes( Bhowmick et al., 2009; Peshenko et al., 2015). This strikes at the difference between the composition of cellular components supporting membrane protein stabilization and transport in cell culture models versus functional photoreceptors. The goal of future experiments is to determine whether these protein localization patterns would be affected by co-expressing GC-1 with rhodopsin, thereby gaining further insight into the underlying intracellular trafficking mechanisms. Finally, GC-1 trafficking was reported to depend on the small protein RD3, which is thought to stabilize both guanylate cyclase isoforms, GC-1 and GC-2, in biosynthetic membranes( Azadi et al., 2010; Zulliger et al., 2015). In the case of GC-1, this stabilization would be complementary to that by rhodopsin and potentially could take place at different stages of GC-1 maturation and trafficking in photoreceptors. Another proposed function of RD3 is to inhibit the activity of guanylate cyclase isoforms outside the outer segment in order to prevent undesirable cGMP synthesis in other cellular compartments( Peshenko et al., 2011a). In summary, this study explains how GC-1 reaches its intracellular destination without containing a dedicated targeting motif, expands our understanding of the role of rhodopsin in photoreceptor biology and extends the diversity of signaling proteins found in GPCR complexes to a member of the guanylate cyclase family. Provided that the cilium is a critical site of GPCR signaling in numerous cell types( Schou et al., 2015), it would be interesting to learn whether other ciliary GPCRs share rhodopsin’s ability to stabilize and deliver fellow members of their signaling pathways.", "role": "user" }, { "content": "Our vision begins with light being captured by the rod and cone photoreceptor cells of the retina at the back of the eye . Photoreceptors have large antennae , termed outer segments , which contain specialized proteins that produce electrical signals when stimulated by light . However , it remains mostly unknown how these signaling proteins are delivered specifically to this part of the cell . A light-capturing receptor called rhodopsin is by far the most abundant component of the outer segment and the only one whose transport route through the cell has been well mapped . By examining mice that had been genetically modified to lack rhodopsin , Pearring et al . have now investigated whether the rhodopsin transport pathway also delivers other signaling proteins to the outer segment . These studies revealed that a protein called guanylate cyclase 1 , which makes a messenger molecule inside rod and cone cells , is the only outer segment protein whose delivery to the outer segment and stability inside the cell rely on rhodopsin . Guanylate cyclase literally ‘piggybacks’ on rhodopsin on its route to the outer segment , as these proteins bind to one another . Therefore , rhodopsin is not just a light-sensing receptor protein; it also serves as a “trafficking guide” for another key protein in the same signaling pathway . As Pearring et al . have shown that the majority of outer segment proteins are delivered independently of rhodopsin , future studies will need to search for alternative protein transport pathways in photoreceptor cells . Whether receptor molecules other than rhodopsin stabilize and deliver fellow members of their signaling pathways to specific cell structures also remains to be discovered .", "role": "assistant" } ]

[ { "content": "Given the following biomedical passages, answer the question succinctly. Ensure your response is precise and limited to the answer only.\n\nQuestion: Which was the first approved tumor treatment using a common biomarker rather than specified tumor locations in the body?\n\nPassages: On May 23, 2017, the US Food and Drug Administration (FDA) approved a treatment for cancer patients with positive microsatellite instability-high (MSI-H) markers or mismatch repair deficient (dMMR) markers. This approach is the first approved tumor treatment using a common biomarker rather than specified tumor locations in the body.", "role": "user" }, { "content": "Keytruda", "role": "assistant" } ]

[ { "content": "Read the provided biomedical research paper and create a concise abstract. Ensure the abstract captures the main points of the paper.\n\nFull Paper:\nmycoplasma pneumoniae is an important cause of respiratory tract infections including community - acquired pneumonia .\nit has been suggested that the pathogen may also play a role in the development of atherosclerosis .\nthis hypothesis is supported by the ability of m. pneumoniae to cause extrapulmonary manifestations affecting the blood vessels , , .\nhowever , others have presented discordant results , so that the role of m. pneumoniae in the pathogenesis of atherosclerosis must still be regarded as unknown , .\nserum iga antibodies are a more reliable indicator for acute m. pneumoniae infection than igm , because specific igm are not mounted regularly in elderly patients , .\nimportantly , the serum level of specific iga declines to normal values earlier after acute infection than the level of specific igm , with a significant decrease 60 days after the onset of disease .\nthe aim of this study was to investigate the role of m. pneumoniae in the development atherosclerosis by repeated testing of specific iga over a period of 6 month .\nninety - one consecutive patients with symptomatic and asymptomatic internal carotid artery ( ica ) stenosis > 70% , who were admitted for surgery march and july 2004 were enrolled in this study .\nthirty - nine patients ( 43% ) had asymptomatic ica stenosis , 32 patients ( 35% ) had transient ischaemic episodes and 20 patients ( 22% ) were operated on for non - disabling stroke .\nall patients were planned for routine eversion endarterectomy ( eea ) of the ica under regional anaesthesia .\nas anaesthetic agent 1% lidocaine was used for a combined superficial and deep cervical block .\nsymptomatic patients with stroke had an interval of less than 6 weeks prior to surgery ; symptomatic patients with transient hemispheric and non - hemispheric symptoms were all operated on within 3 weeks after presentation . for all patients , the following data were assessed : age , sex , clinical stage of carotid artery disease ( cad ) ( right / left ) , degree of stenosis ( right / left ) , body mass index ( bmi ) , alcohol consumption ( gram / week ) , nicotine ( cigarettes / day ) , diabetes mellitus , cholesterol , triglycerides and homocysteine .\npatients on antihypertensive medication or a blood pressure of 140/75 mmhg on repeat measurements were characterized hypertensive .\nmaximum ica stenosis was assessed by magnetic resonance angiography and duplex and stenosis of 70% were an indication for surgery .\nserum was obtained by venipuncture of the antecubital vein using standard tubes ( vacuette edta tubes , greiner bio - one , kremsmuenster , austria ) and centrifugation 10 minutes at 2,000 g. serum was stored at 80c until use . the first serum specimen ( s1 )\nwas taken before surgery , and the second after an interval of 6 months ( s2 ) .\nspecific iga were measured by the seromp iga kit ( savyon diagnostics , ashdod , israel ) according to the manufacturer s recommendations . as indicated by the manufacturer values > 20 bu ( binding units ) were considered positive .\nstatistical analysis was performed by chi squared test ( yates correction ) , using epiinfo 2002 ( cdc , atlanta , ga , usa )\nthe iga seroprevalence at admission ( s1 ) was 18.7% ( 17 of 91 patients ) . in these patients ,\npneumoniae iga after a period of 6 month ( median : 36 bu ; range : 2257 bu ) . among the 74 patients with negative s1 results ,\nthe elisa results and basic clinical data of the 18 patients with 1 result > 20 bu are shown by table 1 ( tab .\nnone of the assessed demographic factors or risk factors for atherosclerosis was associated with iga seropositivity , neither were the degree cavk or the degree of stenosis .\nin this study we found a considerable seroprevalence of iga antibodies to m. pneumoniae in patients with internal carotid artery stenosis .\nhowever , the more remarkable finding was that in the majority of our patients iga remained elevated at essentially constant levels through a period of at least 6 month .\nin contrast , few patients ( 3 ) developed specific iga between the taking of the first and the second serum specimen .\nwe have focused on iga determination in the present study , because specific igm formation may be lacking in the elderly .\nigg antibodies , on the other hand , remain elevated for longtime after infection , which results in a high igg seroprevalence , that can cause interpretation difficulties .\ndetermination of specific iga is a suitable tool for the diagnosis of m. pneumoniae infection .\nit has been shown that after infection specific iga decline to normal values ( i.e. levels below the cut - off value of commercially available tests ) earlier than specific igm .\nhowever , iga - based diagnosis is less established than igm- or igg - based diagnosis , and persistently elevated iga as indicator of chronic infection , although biologically plausible , has to be interpreted with caution .\nit has to be mentioned that differing figures concerning the seroprevalence of iga antibodies to m. pneumoniae in elderly patients have been published , with seroprevalences up to 79% , .\nhowever , the applied assay and the respective cut - off level for positivity is obviously important in this context . by the assay applied in the present study ,\nwe have found a seroprevalence of 13% ( > 20 bu ) and no value > 30 bu among 46 healthy subjects .\nnevertheless , a significant trend to a decrease in antibody level would be expected if the elevated iga levels in our patients should simply reflect past respiratory tract infection .\nit is notable that in the 13 patients with persistently high iga levels , 6 showed an increasing and 6 a decreasing iga level , with the level in one patient remaining constant ( table 1 ( tab .\nan important study negotiating a potential role of m. pneumoniae in the development of atherosclerosis has been provided by maraha et al . , who failed to detect the pathogen in the great majority of 103 atherectomy specimens and degenerative heart valve specimens .\nhowever , it should be considered that some mycoplasma - associated diseases , including severe pneumonia and neurological manifestations , are immunologically mediated and require the presence of the pathogen only in an early stage of the disease , , .\ntherefore , serological methods may be advantageous to explore the association between m. pneumoniae infection and atherosclerosis . in conclusion ,\nwe have applied a new serological approach to investigate the role of m. pneumoniae in the development of atherosclerosis .\nthe results can not be explained throughout by the general seroprevalence , or by past respiratory tract infections with the pathogen , so that they suggest a role for m. pneumoniae in the development of atherosclerosis .\nhowever , it has to be considered that the association between chronic mycoplasma infection and persistently elevated iga antibodies is not yet proven by large - scale epidemiological investigations .\nfuture studies on the potential role of m. pneumoniae in the development of atherosclerosis are warranted .", "role": "user" }, { "content": "background : it has been suggested that mycoplasma pneumoniae may play a role in the development of atherosclerosis , but to date this association is still a matter of debate due to conflicting findings.methods : we have investigated the levels of specific iga antibodies to m. pneumoniae in 91 patients with internal carotid artery ( ica ) stenosis using a commercial kit ( seromp iga ; savyon diagnostics , israel ; cut - off value : 20 binding units ; bu ) . all patients underwent surgery for ica stenosis . from each patient , the first serum sample ( s1 ) was taken before surgery , and the second after an interval of 6 month ( s2).results : the s1 seroprevalence was 18.7% ( 17/91 ) . \n thirteen of the 17 patients with positive s1 levels also remained positive after six month , whereby no decrease of iga level was seen ( median s1 level : 34 bu , range : 2265 bu ; median s2 level : 37 bu , range : 2258 bu ) . \n specifically , six of the patients showed an increased level after 6 months , and six a decrease , with the level remaining constant in one patient . \n in contrast , only 3 of the 74 s1 negative patients became positive for anti - m . \n pneumoniae iga between the taking of the first and the second serum specimen ( p<0.01 ) . \n none of the assessed demographic factors or risk factors for atherosclerosis was associated with iga seropositivity , neither were the degree cavk or the degree of stenosis.conclusion : these findings can not be explained throughout by the general seroprevalence , or by past respiratory tract infections with the pathogen , and therefore may suggest a role for m. pneumoniae in the development of atherosclerosis , since a chronic infection must be assumed .", "role": "assistant" } ]

[ { "content": "Examine the following abstract and identify distinct entities. Focus on extracting entities related to participants, interventions, and outcomes.\n\nPresent your findings in a JSON format like: {\"Participant\": [\"example entity\", ...], \"Intervention\": [\"example entity\", ...], \"Outcome\": [\"example entity\", ...]}. If no entities are found for a category, use an empty list.\n\nAbstract Content:\n\nImpact of MET expression on outcome in BRAF ( V600E/K ) advanced melanoma . AIMS Preclinical data suggest that signalling through the HGF-MET pathway may confer resistance to BRAF inhibition in BRAF ( V600E/K ) melanoma . Therefore , blockade of HGF-MET signalling might be a valid therapeutic strategy , in combination with BRAF inhibition , in BRAF ( V600E/K ) melanoma . The aim of this study was to investigate the clinical relevance of these observations by evaluating the survival impact of MET expression in patients with BRAF ( V600E/K ) advanced melanoma treated with vemurafenib . METHODS AND RESULTS Formalin-fixed tissue blocks were obtained of tumours from patients enrolled in the BRIM2 ( n = 59 ) and BRIM3 ( n = 150 ) trials of vemurafenib in advanced BRAF ( V600E/K ) melanoma . Immunohistochemistry for MET ( SP44 rabbit monoclonal antibody ) was performed with a highly validated assay and clinically validated scoring system . Pretreatment MET expression was frequent at the ≥1 + cutoff ( BRIM3 , 31 % ; BRIM2 , 49 % ) , but relatively infrequent at the ≥2 + cutoff ( BRIM3 , 9 % ; BRIM2 , 19 % ) . Retrospective subset analyses showed that , irrespective of the cutoff used or the treatment arm , MET expression did not show prognostic significance , in terms of objective response rate , progression-free survival , or overall survival . CONCLUSIONS MET is expressed in a proportion of BRAF ( V600E/K ) advanced melanomas . Further analyses on appropriately powered subsets are needed to determine the prognostic and predictive significance of MET in vemurafenib-treated melanoma .", "role": "user" }, { "content": "{\"Intervention\": [\"BRAF inhibition\", \"vemurafenib\"], \"Outcome\": [], \"Participant\": [\"150\", \"59\", \"BRAF ( V600E/K ) advanced melanoma\", \"BRIM3\", \"advanced melanoma\", \"BRIM2\"]}", "role": "assistant" } ]

[ { "content": "Evaluate the given public health statement using the provided research abstract. Your goal is to determine the relationship between the claim and the abstract content.\n\n- \"decision\": Indicate whether the abstract \"SUPPORTS\", \"CONTRADICTS\", or provides \"INSUFFICIENT\" information regarding the claim.\n- \"justification\": List sentences from the abstract that back your decision. If the decision is \"INSUFFICIENT\", leave this list empty.\n\nStatement: The Centers for Disease Control and Prevention (CDC) has recommended that Americans wear cloth face coverings (masks) in public to help slow the spread of COVID-19. \n\nResearch Abstract:\nFace masks are an avenue to curb the spread of coronavirus, but few people in Western societies wear face masks.\nSocial scientists have rarely studied face mask wearing, leaving little guidance for methods to encourage these behaviours.\nIn the current article, we provide an approach to address this issue by developing the 32-item and 8-dimension Face Mask Perceptions Scale (FMPS).\nWe begin by developing an over-representative item list in a qualitative study, wherein participants' responses are used to develop items to ensure content relevance.\nThis item list is then reduced via exploratory factor analysis in a second study, and the eight dimensions of the scale are supported.\nWe also support the validity of the FMPS, as the scale significantly relates to both face mask wearing and health perceptions.\nWe lastly confirm the factor structure of the FMPS in a third study via confirmatory factor analysis.\nFrom these efforts, we identify an avenue that social scientists can aid in preventing coronavirus and illness more broadly - by studying face mask perceptions and behaviours.", "role": "user" }, { "content": "{\"verdict\": \"SUPPORT\", \"evidence\": [\"Face masks are an avenue to curb the spread of coronavirus, but few people in Western societies wear face masks.\"]}", "role": "assistant" } ]

[ { "content": "Evaluate the given public health statement using the provided research abstract. Your goal is to determine the relationship between the claim and the abstract content.\n\n- \"decision\": Indicate whether the abstract \"SUPPORTS\", \"CONTRADICTS\", or provides \"INSUFFICIENT\" information regarding the claim.\n- \"justification\": List sentences from the abstract that back your decision. If the decision is \"INSUFFICIENT\", leave this list empty.\n\nStatement: Other risk factors may also increase your risk for severe illness from COVID-19, including: asthma. lung, heart, liver, or kidney disease.\n\nResearch Abstract:\nThe ongoing outbreak of COVID-19 has been expanding worldwide.\nAs of 17 April 2020, the death toll stands at a sobering 147,027 and over two million cases, this has been straining the health care systems all over.\nRespiratory failure has been cited as the major cause of death but here we present a case about a patient who instead succumbed to severe metabolic acidosis with multiple organ failure.", "role": "user" }, { "content": "{\"verdict\": \"NEI\", \"evidence\": []}", "role": "assistant" } ]

[ { "content": "Examine the given text from a research paper in the field of NLP. Your task is to identify the role of the citation within the context provided. Focus on understanding the intent behind the citation and classify it accordingly.\n\nSection Title:\nNone\n\nText Before Citation:\nAccording to Dalrymple (2001), LFG assumes the following universally available inventory of grammatical functions: SUBJ(ect), OBJ(ect), OBJe, COMP, XCOMP, OBL(ique)e, ADJ(unct), XADJ. The argument list can be empty, as in the PRED value for judge in Figure 1. In Figure 1 the verb FOCUS requires a subject and an oblique object introduced by the preposition on: FOCUS((r SUBJ)(r OBLon)).\n\nCitation Text:\nAccording to Dalrymple ( 2001 ) , LFG assumes the following universally available inventory of grammatical functions : SUBJ ( ect ) , OBJ ( ect ) , OBJe , COMP , XCOMP , OBL ( ique ) e , ADJ ( unct ) , XADJ .\n\nText After Citation:\nOBJe and OBLe represent families of grammatical functions indexed by their semantic role, represented by the theta subscript. This list of grammatical functions is divided into governable (subcategorizable) grammatical functions (arguments) and nongovernable (nonsubcategorizable) grammatical functions (modifiers/adjuncts), as summarized in Table 1. 2 LFGs may also involve morphological and semantic levels of representation. \u0000\u0000\u0000\u0000\u0000\u0000\u0000\u0000 Sample LFG rules and lexical entries.", "role": "user" }, { "content": "Background", "role": "assistant" } ]

[ { "content": "Transform the following sections from a biomedical study into a simple summary for the general public. Focus on making the information accessible and easy to understand.\n\nResearch Heading: Subtypes of Native American ancestry and leading causes of death: Mapuche ancestry-specific associations with gallbladder cancer risk in Chile\nContent:\nAbstract:\nLatin Americans are highly heterogeneous regarding the type of Native American ancestry. Consideration of specific associations with common diseases may lead to substantial advances in unraveling of disease etiology and disease prevention. Here we investigate possible associations between the type of Native American ancestry and leading causes of death. After an aggregate-data study based on genome-wide genotype data from 1805 admixed Chileans and 639, 789 deaths, we validate an identified association with gallbladder cancer relying on individual data from 64 gallbladder cancer patients, with and without a family history, and 170 healthy controls. Native American proportions were markedly underestimated when the two main types of Native American ancestry in Chile, originated from the Mapuche and Aymara indigenous peoples, were combined together. Consideration of the type of Native American ancestry was crucial to identify disease associations. Native American ancestry showed no association with gallbladder cancer mortality( P = 0. 26). By contrast, each 1% increase in the Mapuche proportion represented a 3. 7% increased mortality risk by gallbladder cancer( 95%CI 3. 1–4. 3%, P = 6×10−27). Individual-data results and extensive sensitivity analyses confirmed the association between Mapuche ancestry and gallbladder cancer. Increasing Mapuche proportions were also associated with an increased mortality due to asthma and, interestingly, with a decreased mortality by diabetes. The mortality due to skin, bladder, larynx, bronchus and lung cancers increased with increasing Aymara proportions. Described methods should be considered in future studies on human population genetics and human health. Complementary individual-based studies are needed to apportion the genetic and non-genetic components of associations identified relying on aggregate-data.\nIntroduction:\nDifferences in disease prevalence between Latinos and other populations are well established. Latin Americans and Latino Americans show in general higher incidence rates of gallbladder and stomach cancer, asthma and diabetes, and lower incidences of breast and prostate cancer than non-Hispanic Whites and African Americans[1–10]. Recently much attention has been paid to differences in disease susceptibility according to the individual proportions of Native American, European and African ancestry[11, 12]. On average, Colombians and Puerto Ricans have higher percentages of African ancestry than Mexicans and Chileans, and this potentially translates into differential disease risks, with important implications to health policy[13]. This article focuses on a finer level of genetic heterogeneity, namely on the type of Native American ancestry. Even if two persons from Mexico and Chile have identical Native American proportions, let say equal to 50%, their Native American proportions originate from different native peoples, potentially resulting in unequal disease susceptibilities and prevalences. So far, Latino heterogeneity related to the type of Native American ancestry is not considered in disease prevention and management programs. Present results may contribute to changing this situation. The genome of modern Chileans is the result of genetic admixture between Native Americans from two major indigenous peoples, the Mapuche and the Aymara, Spaniards who reached Chile in the mid-sixteenth century, African slaves who arrived in seventeenth century, and subsequent migrations in the nineteenth and twentieth centuries, mainly from Europe. Recent publications on genetic variability in Chile highlight the relevance of examining Native American ancestry to understand population history[13–16]. Based on genotype data from 313 Chileans, Eyheramendy et al. confirmed previously reported larger contributions of European men and Native American women, and attributed the increased Native American proportion in the South of the country to the late occupation of this territory by non-indigenous immigrants[14]. The predominance of Native American ancestry in the south of Chile was corroborated by Ruiz-Linares et al., who utilized 1561 Chilean genotypes to investigate the geographic variation in ancestry in a large Latin American study[13]. The goal of the present study is markedly different. We focus here on the relationship between top causes of mortality and the two main types of Native American ancestry in Chile. We conduct first an aggregate-data study based on 1805 subjects, and then validate an identified association between Mapuche ancestry and gallbladder cancer using individual data from 64 patients and 170 healthy controls with and without a family history. In total, the present study relies on genome-wide single nucleotide polymorphism data from 2, 039 admixed Chileans and 639, 789 country-wide registered deaths between 2005 and 2011. It aims to illustrate the need to consider fine-scale Latino heterogeneity to advance in the understanding of disease etiology, and to personalize healthcare. Our investigation benefited from 1) the geography of Chile, a country with over 4, 300 km from north to south but only 200 km from east to west which shows large regional differences in disease-specific mortality rates, 2) the genetic architecture of Chileans which is largely composed of European and Native American ancestry and presents a low( 3%) African component, and 3) the clear separation of the two investigated subcomponents of Native American ancestry which varies greatly from Northern to Southern Chile.\nDiscussion:\nWe report here for the first time on the relationship between leading causes of death and the type of Native American ancestry. Fortunately, awareness of the importance of accounting for genetic diversity within ethnic groups in public health is raising fast[19, 20]. The need to estimate ancestry components using reference individuals who reflect the actual composition of the study population was also a relevant finding of the present investigation. Previous studies have demonstrated the need of accounting for fine-scale ancestry patterns to identify possible associations with biomedical traits[11, 12, 21]. Among Latinos, Puerto Ricans show higher mortality rates due to asthma than Mexican Americans[22–25]. Considering this difference, which could be attributed to the increased African component of Puerto Ricans, or to sub-continental differences in European ancestry with Mexicans, may be critical to individualize medicine approaches tailored to asthmatics from different ethnic groups. Another novelty of the present study was the identification of the Mapuche-Aymara ancestry axis as the third major component of genetic variability in Chile. The low genetic distance between Mapuche and Aymara reference individuals( Fst = 0. 038) contrasts with larger genetic differences observed among other Native American indigenous peoples[21]. The geography and the settlement history of Chile, which was principally populated from North to South, likely explain this low genetic distance. Investigation of the subcomponents of Native American ancestry may help to refine previously identified associations with human disease. For example, combination of the Mapuche and Aymara subcomponents of Native American ancestry in Chile resulted in an overall underestimation of the Native American percentage. We identified an association between asthma mortality and Mapuche ancestry but, due to opposite effects for Mapuche and Aymara proportions, the association between Native American ancestry and asthma did not reach statistical significance. In agreement with previous studies, the first principal component of genetic variability among Chileans separated African from non-African contributions, and Chileans showed on average a low percentage of African ancestry[13, 14]. The bulk of the study population was dispersed between Native American and European reference individuals, and this dispersion constituted the second component of genetic variability. Examination of the Mapuche and Aymara proportions permitted identification of novel associations that are relevant from both a social and a public health context. Increasing Mapuche ancestry was associated with a lower educational level and a lower socioeconomic status in Chile. From the point of view of public health, increasing Mapuche proportions were associated with increased mortalities due to certain types of cancer( gallbladder, esophagus and stomach tumors, malignant neoplasms without specification of site and myelodysplastic syndromes). Increasing Aymara percentages corresponded to increased mortality risks by bladder, larynx, skin, and bronchus and lung neoplasms. Although the relative contribution of socioeconomic factors, access to health services and therapy response to mortality differences in Chile needs further investigation, results from the present study suggest that finer gradation of Latino and Native American ancestry may have important implications for prevention and disease management, not only in Chile but in other parts of the world. The possible confounding of some of the identified associations between ancestry proportions and disease-specific mortality risks by geographical, socioeconomic and cultural factors was a limitation of present results based on aggregate-data. Regarding geography, the association between Aymara ancestry and non-melanoma skin cancer was probably related to the high ultraviolet radiation in the north of Chile[26]. The relationship between Aymara proportions and mortality due to lung and bladder cancers could be attributed to a large extent to the high concentration of arsenic in drinking-water in the north of Chile[27]. Although confounding by socioeconomic factors cannot be ruled out, access to individual information on educational level, socioeconomic status and salary represented a clear advantage of the present aggregate-data study over plain ecological investigations[28]. This permitted adjustment of the estimated mortality risk ratios for possible confounders at both the individual( Table 1) and the regional levels( for example, hospitalization rates due to gallbladder removal as surrogate of access to the health system in sensitivity analyses). Culture and ancestry go often together, but it should be kept in mind that our study relied on admixed people with a continuous gradient of ancestry. In other words, two hypothetical individuals with 25% and 30% Aymara proportions would probably present a similar physical appearance and possibly be exposed to similar culture-related environments. Yet according to our findings, their mortality risks due to esophageal cancer would be markedly different, precisely 5 x 3. 7% = 18. 5%. Summing up, present aggregate-data results need future investigations based on individual data to apportion the different components of the complex relationship between genetic ancestry and human disease. Consideration of individual ancestry proportions may boost the personalization of prevention and disease management programs[19–21]. Less healthy lipid profiles have been found in Mexican Americans than in European Americans, and this information has been translated into tailored prevention programs for associated diseases[29]. Hispanics and European Americans show higher rates of hepatitis C viral clearance after treatment than African Americans, and precision medicine has recognized the need of clinical trials with African American participants to decrease treatment disparities[30]. In agreement with our findings( Supplementary S2 Table), European ancestry has been associated with cardiovascular disease, and European-ancestry specific susceptibility variants for heart failure have been identified, adding plausibility to reported associations based on aggregate-data[31, 32]. It is relatively well-known that race and ethnic group are inaccurate predictors of disease risk and response to treatment, but this imprecision has been largely attributed to the differential ancestry percentages. For example, Latinos from Mexico show average Native American( African) proportions equal to 56%( 5%), compared to 29%( 11%) for Colombian Latinos[13]. The present study goes one step further and demonstrates the added value of considering ancestral groups which reflect the actual composition of the study population. The average Native American proportions of Chileans in the De Arica y Parinacota and the De los Ríos regions were similar around( 58%), but the Mapuche and Aymara percentages were markedly different, 54% Mapuche and 6% Aymara in the De los Ríos compared to 30% Mapuche and 29% Aymara in the De Arica y Parinacota regions, resulting in considerably different disease-specific mortality rates and associated healthcare needs. Gallbladder cancer is a major health problem in Chile, where the disease represents the second leading cause of cancer death in women after breast cancer. While the association between Native American ancestry and gallbladder cancer is well established, an added value of the present findings lies in the refinement and accurate quantification of the strength of this association[1, 18, 33–36]. We found that the mortality risk due to gallbladder cancer increased by 3. 7%( 95% CI of 3. 1 to 4. 3%) per 1% increase in the Mapuche proportion. The statistical analysis of validation data from sporadic and familial gallbladder cancer cases, and from unaffected individuals, was consistent with this association: a 1% increase in the Mapuche component corresponded to a 2% increased risk of developing gallbladder cancer. Resampling results suggested that the relationship between Mapuche ancestry and gallbladder cancer was robust against the differential number of individuals per region in the aggregate-data study. Sensitivity analyses revealed a minor contribution of the differential access to the health system to this association, and hinted that the use of Mapuche reference individuals with larger Native American proportions may result in stronger association effects. These results may have important repercussions at the population and individual levels given the large variability of Mapuche proportions in the Chilean population. In the present study, the first( third) quartiles of Mapuche proportions were 28%( 43%) in the aggregate-data, and 38%( 49%) in the validation dataset, respectively. At the population level, the Chilean government financially supports gallbladder removal for individuals between ages 35 and 49 years to prevent gallbladder cancer; prophylactic cholecystectomy could be also indicated in other high risk populations[37, 38]. The difference in Mapuche proportions between the De los Ríos and the De Arica y Parinacota regions translates into an expected 24x3. 7 = 89% difference in gallbladder cancer mortality, which may point to the necessity of intensified prevention measures in southern regions of the country. At the individual level, people with relatives affected by gallbladder cancer could opt for estimating their risk of developing gallbladder cancer relying on individual ancestry percentages, and make medical decisions based on this information. Future studies are needed to develop and validate risk prediction models which incorporate genetic ancestry and other risk factors in order to personalize gallbladder cancer prevention. In summary, admixed Chileans show two main types of Native American ancestry: Mapuche and Aymara. Increasing Mapuche proportions are specifically associated with an increased mortality due to asthma and gallbladder cancer, and with a decreased mortality due to diabetes. Increasing Aymara percentages correspond to increased risk of death by melanoma and bladder, larynx, skin, and bronchus and lung neoplasms. These results suggest that finer gradation of Native American ancestry has important implications for unraveling of disease etiology and disease prevention.", "role": "user" }, { "content": "A lot of attention has been paid to Latino heterogeneity related to individual proportions of Native American , European and African ancestry . The importance of the type of Native American ancestry for health , however , has hardly been studied . Here we examined genetic data from 2 , 039 admixed Chileans to investigate possible associations between top causes of death and the two major types of Native American ancestry in Chile . Our findings demonstrate the necessity of suitable surrogates for ancestry estimation which mirror the actual composition of the study population , and the advantage of considering fine-scale Latino heterogeneity for unraveling of disease etiology and personalized healthcare .", "role": "assistant" } ]

[ { "content": "Transform the following sections from a biomedical study into a simple summary for the general public. Focus on making the information accessible and easy to understand.\n\nResearch Heading: Noise Management by Molecular Networks\nContent:\nAbstract:\nFluctuations in the copy number of key regulatory macromolecules( “noise”) may cause physiological heterogeneity in populations of( isogenic) cells. The kinetics of processes and their wiring in molecular networks can modulate this molecular noise. Here we present a theoretical framework to study the principles of noise management by the molecular networks in living cells. The theory makes use of the natural, hierarchical organization of those networks and makes their noise management more understandable in terms of network structure. Principles governing noise management by ultrasensitive systems, signaling cascades, gene networks and feedback circuitry are discovered using this approach. For a few frequently occurring network motifs we show how they manage noise. We derive simple and intuitive equations for noise in molecule copy numbers as a determinant of physiological heterogeneity. We show how noise levels and signal sensitivity can be set independently in molecular networks, but often changes in signal sensitivity affect noise propagation. Using theory and simulations, we show that negative feedback can both enhance and reduce noise. We identify a trade-off; noise reduction in one molecular intermediate by negative feedback is at the expense of increased noise in the levels of other molecules along the feedback loop. The reactants of the processes that are strongly( cooperatively) regulated, so as to allow for negative feedback with a high strength, will display enhanced noise.\nIntroduction:\nSome molecular processes involved in cellular regulation operate in a regime of low molecule numbers( a few to tens per cell). Inevitable fluctuations in reaction rates, induced by thermal noise, can then bring about significant heterogeneity in isogenic populations by causing fluctuations in copy numbers of molecules[1]–[6]( reviewed in[7]–[10]). Fluctuations arise in molecule levels because of the asynchronous occurrence of synthesis and degradation events. The extent of noise in the molecule number of a species is commonly captured by a measure of noise significance, defined as the variance in the copy number divided by the squared mean copy number, as determined from many single-cell snapshots for a population of( isogenic) cells. For molecules engaged in equilibrium reactions, this ratio is of the order of 1 divided by their mean copy number, making noise in such molecule numbers irrelevant whenever the molecule numbers exceed 100. For systems away from thermodynamic equilibrium and depending on kinetics and stoichiometry, noise can become appreciable even at high copy numbers for molecules( hundreds to thousands per cell)[11]. The noise in a specific molecule is partially determined by the molecules it forms a network with, due to noise propagation[12]–[14]. A molecule with a large copy number might display large noise, due to its communication with a molecular species with a low copy number. This may explain much of the noise found in the levels of many proteins. Despite their high mean levels, many of them are short-lived and are translated from mRNAs occurring at low levels[7],[8]. Our understanding of the functional consequences of particular network structural aspects, such as feedback, cascades, cooperative enzymes, and time-scale separation, has profited greatly from numerous theoretical studies in the last decades( e. g.[15]–[21]). Many of these studies adopted a metabolic control analysis perspective on metabolic and hierarchical networks; where the latter networks may involve signaling and gene expression.[17],[22]–[24]( recently reviewed in Bruggeman et al.[25]). They focussed on deterministic( macroscopic) network properties rather than taking a stochastic( mesoscopic) perspective. Hierarchical networks consist of modules, called levels in this framework, that are composed out of reaction networks where molecules affect the rates of processes as reactants and effectors. Inter-level interactions occur via effector interactions only; this means that the regulating molecules of one level act as activators and inhibitors of processes in another level without being consumed in the latter level. Examples of hierarchical networks are gene-expression and signaling cascades or metabolic systems involving gene expression and signaling. Metabolic control analysis and its theoretical extensions have shown that sensitivity amplification and feedback in hierarchical networks allows for a repertoire of mechanisms for ultra- or insensitive( robust) responses to changes in particular signals and it has given us insight into distribution of control in metabolic networks[15],[16],[23],[24],[26]–[28]. These mechanisms also play a pivotal role in noise propagation through signaling and gene-expression cascades as indicated by experimental work and numerical simulations[12]–[14]. Noise transmission depends on the strength of macromolecular interactions( sensitivity) and on time scales. High frequency fluctuations in the copy number of one molecule can only transfer to other molecules if it affects an enzyme( or uncatalyzed process) that operates at even faster( internal) kinetics. If the reaction catalyzed by that enzyme involves other molecules, then noise will be transferred to the molecule numbers of these reactants if the enzyme is fast enough to track the fluctuations in the regulator. If the enzyme was not sensitive to the regulator, noise transfer would not have occurred. Stochastic( mesoscopic) dynamics of molecular networks can be described by the so-called master equation, which models a Markov process( with continuous time and discrete-state space). It specifies the rate of change of the probability density functions for all the copy numbers of molecules( the system's state) over time[29]. Linear noise approximation( LNA)[11],[12],[29],[30] provides a first order approximation of the dynamics of the probability densities described by the master equation. It provides exact solutions for networks described by linear rate equations( e. g. of the sort, but neither nor). We will reformulate LNA in terms of response analysis( RA), developed within the framework of metabolic control analysis[24],[26],[31], with the aim of merging the two methods. In this way, we can exploit the extensive knowledge about control and responses of hierarchical molecular networks within metabolic control analysis for studying the principles of noise propagation. In the first section, we introduce LNA and RA to derive the basic equation of the new, combined theory. Subsequently, we describe how noise in a single molecular intermediate is received and transmitted by its surrounding molecular network. We derive equations that indicate how noise is transmitted along cascades and how it is modulated by processes that operate at certain time-scales, feedback and feedforward loops. The analysis yields new insight into potent mechanisms for noise reduction, as well as in which mechanisms may be at the origin of the frequently observed heterogeneity of clonal cell populations.\nDiscussion:\nIn this paper, we presented a conceptual and mathematical framework that gives insight into noise management by molecular networks. Intrinsic noise in the copy number of a molecule was shown to derive from the fluctuations in the birth( synthesis) and death( degradation) rates of that molecule. The noise that a molecule exhibits in a network equals the sum of its intrinsic noise and an additional extrinsic noise component. The extrinsic noise component arises from molecular networking. Modular response analysis and hierarchical control analysis exploit the hierarchical design of most signaling networks and of transcription and translation cascades and are each extensions of metabolic control analysis[22]–[24],[26],[31]. This work presented a merger of noise and response analysis. We have focussed solely on hierarchical networks composed out of levels even though the methods outlined in this paper can be straightforwardly generalized to non-hierarchical networks. Where on the one hand our methodology is innovative because of its tight link with metabolic and hierarchical control analysis it is similar, on the other hand, to the approaches developed by Paulson[9],[12]. The two approaches both derive from linear noise approximation( LNA) as an approach to estimate noise in molecular networks. Paulsson's reformulation of LNA offers a description in terms of concepts that draw on analogies from physics whereas we take a more control-centric perspective. Our approach makes many of the results within metabolic control analysis, e. g. dealing with cascades, feedback, ultrasensitivity, and robustness, applicable to the analysis of noise propagation. Another such link with control theory is apparent in the frequency domain approach to the analysis of noise[47],[48] and control[49]. Negative autoregulation( NAR; Figure 2) accelerates the response of small gene networks, e. g. through a transcription regulator inhibiting it's own transcription[43]. For the and motifs to have the same steady state flux a higher synthesis rate in cells is needed to compensate for the inhibition by the negative feedback at steady state. The consequential reduction in time scale enables a faster dissipation of fluctuations and makes this network design more noise resistant( evident from Eqs. 6 & 11, and discussed in the accompanying sections). The noise of NAR motifs has been analyzed experimentally using synthetic gene circuits[3],[13],[50]–[52]. Besides NAR other mechanisms have been shown to reduce noise levels, i. e. dimerization of transcription factors[53], polycistronic mRNA[54], regulated protein degradation[55], and DNA looping[56]. Swain studied two variants of negative autoregulation in transcription and translation and showed that post-transcriptional regulation is a more potent noise reducing mechanism than post-translational regulation[54]. These studies are typically theoretical studies and experiments have yet to be performed to investigate whether these mechanisms influence noise management in particular cases and to significant extents. Some of these proposed mechanisms for noise reduction rely on stoichiometric constraints besides regulatory influences. The approach discussed in this work only considered regulatory influences. When comparing the hierarchical system in Figure 2 with the network where and have a stoichiometric and regulatory coupling and taking the kinetics the same, i. e. for the hierarchical case the rate of degradation and synthesis both equal, the difference between the noise in between the two systems corresponds to. This indicates that the reduced correlation between molecule copy numbers in hierarchical networks, due to the absence of stoichiometric relations, increases noise. Levine and Hwa[33] have considered noise in metabolic networks where the coupling between molecules is via mass flow and, in addition, possibly( allosteric) effector interactions. They found for metabolic networks driven by a product-independent flux, a pump, and composed out of enzymes, which are only sensitive to their substrate concentration, that the noise in a metabolite is independent of all other metabolites. They found that this result is fairly robust to alterations in pathway design and enzyme kinetics. This result is related to the concept of slave enzyme as defined in metabolic control analysis. Enzymes that are only sensitive to their substrates have been termed slave enzymes[35]. The steady-state concentration of any metabolite in a linear pathway composed out slave enzyme is then only determined by the pump speed and the kinetic properties of the consuming enzyme, irregardless of the number of enzymes in the pathway[35]. Changes in their concentrations can then only be brought about by a change in the pump speed or consuming enzyme level. Levine and Hwa[33] showed that the noise in a slave metabolite levels is also robust to the properties of other enzymes except for those of the consuming enzyme. How noise in enzyme levels brings about noise in metabolic flux is largely unexplored. We think that this is an important topic perhaps more important than noise in metabolite levels as they are typically large. Noise in metabolism is then much more likely to occur through noise in protein levels as their copy numbers tend to be smaller than metabolite levels and they can suffer from bursts[57]. Many experiments have shown the occurrence of transcription bursts[5],[57]–[61]. In prokaryotes, these have been shown to enhance adaptation potential[59]. Occasional fluctuations in the binding of repressors at the operators of repressed operons have been shown to cause bursty mRNA synthesis[57],[59],[60]. Hereby, some cells within an isogenic population have an adaptive advantage if the corresponding environmental change occurs purely by chance[59],[62]. The origin of bursts in eukaryotic transcription is most likely different and related to an interplay between transcription factor, and chromatin remodeling dynamics[58],[61]. LNA has been extended to incorporate bursts[5],[63] and indicates that bursts strongly enhance noise. Singh and Hespanha[64] were able to express the noise in protein level as function of the burst size and its variance. They show that noise increases with increasing burst and analyzed under which conditions noise can be reduced through auto-regulatory negative feedback( see also Friedman, Cai and Xie[65]). They find that negative feedback can both enhance and reduce noise. When transcription occurs in bursts, the waiting times for consecutive mRNAs become non-exponentially distributed and even doubly exponential[60],[66],[67]. A general stochastic theory for molecular networks that incorporates bursts and birth and death processes having non-exponential waiting time distributions is currently lacking. Such a theory, should offer deeper understanding of the constraints imposed by the stochastic nature of single cells as well as of potential benefits. At present, approximate stochastic theories, such as the one presented in this work, apply to Markov systems where all events are assumed to have a memoryless( exponential) waiting time distribution. This Markov assumption can be valid even if processes have non-exponential waiting distributions provided they do not function in synchrony and many process copies function simultaneously[67]. On the other hand, phenomena such as epigenetics, and cell heterogeneity that is inheritable, without us knowing of the determining molecular factor, suggests that extensions of the theory to non-Markovian situations might be useful.", "role": "user" }, { "content": "Within cells , fluctuations in molecule numbers are inevitable , since the synthesis and degradation of molecules are not synchronised . Such molecular noise can be transferred to other molecules through regulatory interactions . Noise in molecular networks , and especially in gene expression , has been studied extensively over the past years , both experimentally and through mathematical modelling . In this work , we present a theoretical framework that merges concepts derived from metabolic control analysis ( which was originally developed to describe the control in metabolic pathways ) with linear noise approximation ( a concept from statistical physics ) . This framework is useful to analyse how noise propagates through molecular networks , how noise can be managed within the networks and how different network designs reduce or enhance noise . The present theory makes use of the natural , hierarchical organization of regulatory networks and makes their noise management more understandable in terms of network structure . Within this paper , we apply the framework to signaling and regulatory cascades , and analyse how feedback and time scale separation influence noise propagation in molecular networks .", "role": "assistant" } ]

[ { "content": "Analyze the given paragraph from COVID-19 research. Determine the relevant topics discussed in the text. Your response should be a JSON array containing the identified topics. Ensure the output is a valid JSON array with no additional commentary.\n\nText:\n\nGinkgolic acids (GA) are alkylphenol constituents of the leaves and fruits of Ginkgo biloba. GA has shown pleiotropic effects in vitro, including: antitumor effects through inhibition of lipogenesis; decreased expression of invasion associated proteins through AMPK activation; and potential rescue of amyloid-beta (Abeta) induced synaptic impairment. GA was also reported to have activity against Escherichia coli and Staphylococcus aureus. Several mechanisms for this activity have been suggested including: SUMOylation inhibition; blocking formation of the E1-SUMO intermediate; inhibition of fatty acid synthase; non-specific SIRT inhibition; and activation of protein phosphatase type-2C. Here we report that GA inhibits Herpes simplex virus type 1 (HSV-1) by inhibition of both fusion and viral protein synthesis. Additionally, we report that GA inhibits human cytomegalovirus (HCMV) genome replication and Zika virus (ZIKV) infection of normal human astrocytes (NHA). We show a broad spectrum of fusion inhibition by GA of all three classes of fusion proteins including HIV, Ebola virus (EBOV), influenza A virus (IAV) and Epstein Barr virus (EBV). In addition, we show inhibition of a non-enveloped adenovirus. Our experiments suggest that GA inhibits virion entry by blocking the initial fusion event. Data showing inhibition of HSV-1 and CMV replication, when GA is administered post-infection, suggest a possible secondary mechanism targeting protein and DNA synthesis. Thus, in light of the strong effect of GA on viral infection, even after the infection begins, it may potentially be used to treat acute infections (e.g. Coronavirus, EBOV, ZIKV, IAV and measles), and also topically for the successful treatment of active lesions (e.g. HSV-1, HSV-2 and varicella-zoster virus (VZV)).", "role": "user" }, { "content": "[\"Mechanism\"]", "role": "assistant" } ]

[ { "content": "Analyze the given text to identify specific entities. Focus on extracting relevant data.\n\nProvide your findings in JSON format. Each category should list the entities found.\n\nText:\n\nContinuous IV Crotalidae Polyvalent Immune Fab (Ovine) (FabAV) for selected North American Rattlesnake bite patients. BACKGROUND: In patients bitten by North American rattlesnakes and treated with Crotalidae Polyvalent Immune Fab (Ovine) (FabAV), late hematologic abnormalities-persistent, recurrent, or late, new onset of hypofibrinogenemia, prolonged PT/INR, prolonged PTT, and/or thrombocytopenia beyond 48 h post-envenomation-are common, difficult to manage, and may result in morbidity and mortality are common, difficult to manage, and may result in morbidity and mortality. The optimal management of late hematologic abnormalities, particularly the use of further treatment with antivenom, has not been well defined. The current FabAV treatment regimen is to give antivenom as a bolus dose over a one-hour period. We describe our experience using a continuous intravenous infusion of FabAV for late hematologic effects and/or associated bleeding complications in rattlesnake envenomation. METHODS: This is a retrospective, observational case series of patients envenomated by North American rattlesnakes at three medical centers managed with a continuous intravenous infusion of FabAV for late hematologic abnormalities and/or associated bleeding complications. Indications, dilution and infusion protocols, and duration of therapy were individualized. RESULTS: Five cases were identified between July 2010 and September 2011. All patients had profound late hematologic abnormalities and/or were associated with bleeding complications. Several patients had received repeat bolus infusions of FabAV, with or without human blood products, with either inadequate or only transient beneficial response. All patients were then managed with a continuous intravenous infusion of FabAV and all appeared to respond to the continuous intravenous infusion of FabAV, titrated to effect, with cessation of progression and, in most cases, improvement in hematologic abnormalities. Rates of infusion varied from 2 to 4 vials per 24 h (mean = 3.1 ± 0.4 vials/day). The termination of FabAV infusion was between day 6 and day 14 from the time of envenomation (mean = 10 ± 3 days), after which hematologic values were normalized or were normalizing in all patients and continued to do so. DISCUSSION: The use of FabAV as a continuous intravenous infusion, particularly after the acute phase of envenomation has passed, provides a continuous source of circulating antibodies to neutralize venom components reaching circulation from tissue stores and allows natural replenishment of hematologic factors such as platelets and/or fibrinogen. This method is an efficient use of FabAV, avoiding the wasteful excess of a bolus dose, may be more effective, eliminating the potential for destruction of hematologic factors when protective antivenom levels are lost between bolus FabAV doses, and appears to be safe. Further assessments of the stability and sterility of the product during infusion are needed. The need to continue hospitalization is the major drawback, but continued observation and inpatient care may be needed for other indications (e.g. bleeding) in this subset of patients. CONCLUSIONS: A continuous intravenous infusion of FabAV between 2 and 4 vials per day, titrated to effect, and continued for 6-14 days post-envenomation appeared to be associated with reversal of late hematologic effects of rattlesnake envenomation and, when combined with indicated human blood products, control of significant bleeding. Continuous intravenous infusion of FabAV may be safer, more efficacious, and more cost-effective than observation without FabAV treatment or as-needed bolus dosing in selected patients with late hematologic abnormalities.", "role": "user" }, { "content": "{\"Chemical\": []}", "role": "assistant" } ]

[ { "content": "You will be presented with the full text of a scientific research paper. Write an abstract summarizing the key points. Your response should contain only the abstract without any other text.\n\nArticle text:\nit is common to define pdrs as regions where stellar far ultraviolett ( fuv : 6 ev@xmath0 13.6 ev ) radiation dominates the physical and chemical properties of the local interstellar medium ( ism ) .\nfuv radiation is predominantely produced in massive stars , which do not live long enough to exit their parental cloud of gas and dust within their lifetime .\npdrs are the products of the strong mutual feedback between young massive stars and their parental clouds and hence closely related to the process of star formation ( sf ) .\nmetallicity ( @xmath1 ) is thought to affect the fragmentation properties of gravitationally unstable gas , especially in the early universe ( bromm _ et al .\n_ @xcite ; schneider _ et al . _\nthis should also affect the initial mass function ( imf ) .\nhowever , jappsen _ et al .\n_ @xcite have shown , that the cooling of hot , very low-@xmath1 gas does not seem not to depend on metallicity , since it is dominated by h@xmath2 cooling .\nhence , the cooling depends on the amount of h@xmath2 available for cooling , which might still be a function of metallicity due to the fact that molecular hydrogen is formed on metallic surfaces , i.e. dust .\nfigure [ influence ] lists the most prominent metallicity effects .\nan altered metallicity affects the physics ( primarily energy balance and radiative transfer ) and the chemistry of pdrs .\nthe most important , direct effects are altered elemental abundances leading to a different chemical structure and different total column densities of important species like c@xmath3 , c , and co as well as an altered dust - to - gas ratio @xmath4 .\na lower @xmath4 leads to a weaker attenuation and fuv radiation penetrates deeper into the cloud , destroying fragile molecule up to larger depths . additionally , gas heating by fuv photons can act deeper in the cloud leading to a different temperature structure compared to solar metallicity pdrs . on the other hand ,\nthe probability for a photon to escape the cloud is increased , improving the cooling efficiency at any particular depth while the smaller elemental abundance reduces the cooling rate .\nobservations of low metallicity environments also confirm that the dust composition changes at lower @xmath1 .\nthe pah ( polycyclic aromatic hydrocarbons ) fraction drops significantly ( draine _ et al . _\n@xcite , madden _ et al . _\npahs dominantly contribute to the total photoelectric heating ( pe ) efficiency , thus , at lower values of @xmath1 the pe efficiency is significantly diminished .\n_ @xcite also showed , that the spectral shape of the fuv radiation is different in low @xmath1 dwarf galaxies .\nreduced metallicities lead , for a given stellar type , to hotter main sequence temperatures and to harder , i.e. more energetic , spectral seds .\nthis may affect the dust composition via evaporation and photodissociation processes and leads to a different pe efficiency .\nsince all these effects are non - linear and mutually coupled it is very difficult to give an analytical solution and one has to rely on numerical computations .\nsometimes the results are completely counter - intuitive like displayed in figure [ invertedt ] .\nthe heating and cooling efficiencies at the cloud surface depend on parameters like density @xmath5 , metallicity and fuv intensity @xmath6 . with increasing fuv intensities and densities above @xmath7 @xmath8 , the dominant heating contribution shifts from h@xmath2-deexcitation to photoelectric ( pe ) heating ( c.f .\n_ @xcite ) . since @xmath9 is much less effective for @xmath10 compared to the cooling terms , which scale linearly with @xmath1 , the gas temperature drops if @xmath6 increases , i.e. if we move closer to the fuv source !\nvice versa this means , a hypothetical cloud gets hotter the further away it is placed from a strong fuv source . even though this might be an academic example due to its particular assumptions , it demonstrates the difficulty in predicting metallicity effects .\nan inversion occurs , i.e. the surface temperature drops for an intenser fuv illumination . ]\nthe model results presented here are computed with the kosma-@xmath11 pdr code .\n( stoerzer _ et al . _\n@xcite , rllig _ et al . _\nthis code features spherical geometry and an isotropical fuv irradiation .\nit calculates the chemical and physical cloud structure as function of radius as well as the total cloud emission .\nthe metallicity is a free model parameter and changes the elemental abundances and the gas - to - dust ratio .\nthe chemical network in kosma-@xmath11 is fully modular and individual species can be easily added to or removed from the network .\nrecently , the code has been expanded to calculate the dust temperatures and continuum emission for any given dust distribution ( rllig & szczerba @xcite ) .\nthe model setup can be easily expanded to clump ensembles as presented by cubick _\n( this issue ) to calculate the pdr emission of a large , complex superposition of differently sized clouds .\n_ @xcite gives an overview over pdr modelling as well as a comparison between a number of different model codes .\nthe kosma-@xmath11 results are also available online ( http://www.astro.uni-koeln.de/workgroups/theo_astronomy/pdr/ ) .\n* left : * photodissociation rates of h@xmath2 ( black ) and co ( red ) vs. depth [ cm ] . *\nright : * chemical abundances vs. depth .\nthe lower metallicity leads to a lower abundance at the surface of the cloud .\nadditionally , the weaker shielding shifts the typical h - h@xmath2 and c@xmath3-c - co transitions deeper into the cloud . ] . * left : * photodissociation rates of h@xmath2 ( black ) and co ( red ) vs. depth [ cm ] . *\nright : * chemical abundances vs. depth .\nthe lower metallicity leads to a lower abundance at the surface of the cloud . additionally , the weaker shielding shifts the typical h - h@xmath2 and c@xmath3-c - co transitions deeper into the cloud . ]\na reduced metallicity leads to a decreased shielding of fuv radiation . in the left panel in figure [ shielding ] we compare the h@xmath2 and co photodissociation rates for @xmath12 and @xmath13 .\nthe right panel shows the chemical abundances vs. depth .\nthe lower metallicity leads to a lower abundance of all metallic species at the surface of the cloud . additionally , the weaker shielding shifts the typical h - h@xmath2 and c@xmath3-c - co transitions deeper into the cloud leading to an almost negligible amount of co in the @xmath12 case while the c@xmath3 column depth is much less affected .\nand co(1 - 0 ) surface brightnesses of an ensemble of model pdrs vs. metallicity .\nthe red lines show the ratio [ cii]/co(1 - 0 ) .\n* right:*[cii ] survey results : comparing normal metallicity regions with low - metallicity galaxies ( from madden @xcite).,title=\"fig : \" ] and co(1 - 0 ) surface brightnesses of an ensemble of model pdrs vs. metallicity .\nthe red lines show the ratio [ cii]/co(1 - 0 ) .\n* right:*[cii ] survey results : comparing normal metallicity regions with low - metallicity galaxies ( from madden @xcite).,title=\"fig : \" ] the reduced column densities of the more fragile species at lower metallicities are visible as lower surface brightnesses of the pdr .\nco , being one of the most important chemical species , suffers strongly from the weak shielding due to low @xmath1 .\nfigure [ ciivsco ] compares the ensemble averaged clump emission ( see below ) of [ cii ] , and co(1 - 0 ) vs. metallicitiy ( on the 12+log(o / h ) scale ) . for lower metallicity values ,\nthe co surface brightness decreases significantly .\nthis is a combination of reduced column densities plus a much smaller projected area of the co core of the cloud due a transition from c to co at much higher depths .\nthis projection effect is particularly strong in the low density case @xmath14 @xmath8 , visible as kink in the co curve at 12+log(o / h)=8.4 .\nthe right panel in figure [ ciivsco ] , taken from madden @xcite , shows the [ cii ] intensity vs. co(1 - 0 ) comparing normal metallicity regions with low - metallicity galaxies .\nlines of constant @xmath15}/i_\\mathrm{co}$ ] run diagonally across the plot .\nthe figure clearly shows the metallicity dependence of the [ cii]/co ratio .\na similar behavior has been found by nakagawa _\n@xcite in low metallicity clouds in the large magellanic clouds ( lmc ) .\nthe ratio @xmath15}/i_\\mathrm{co}$ ] is a good measure of pdr emission relative to the emission of the cold molecular material and is a good indicator of star formation .\nactive star formation in the milky way and in nearby star burst galaxies shows a ratio @xmath15}/i_\\mathrm{co}=6300 $ ] while dwarf galaxies show ratios between 6000 and 70000 .\nthis makes dwarf galaxies one of the prime targets to study low metallicity pdrs . due to their small angular size , single dish far - infrared ( fir )\nobservations of dwarf galaxies are unable to resolve individual molecular clouds .\nhence we apply a clump ensemble approach ( cubick _ et al . _\n@xcite ) to model the beam averaged pdr emission of these galaxies .\nfigure [ ngc6822 ] compares the model results for the pdr emission of ngc 6822v , an hii region complex in the dwarf irregular galaxy of the local group at a distance of 470 kpc and a @xmath16 ( 12+log(o / h)=8.37 ) , with fir observations . the blue crosses in figure [ ngc6822 ] show the results for a single component model , i.e. the galaxy is assumed to consists of numerous identical model clouds .\nthe red crosses denote a clump - mass distribution @xmath17 and mass - size relation @xmath18 . taking into account the observed mid-@xmath19 co and fine - structure transitions\nit is not possible to find a good model fit for a single component model . for a clump ensemble\nwe derive a mean gas density @xmath20 @xmath8 , @xmath21 , @xmath22 . 99 bromm , v. ; ferrara , a. ; coppi , p. s. ; larson , r. b. , 2001 , mnras , 328 , 969 cubick , m. , stutzki , j. , ossenkopf , v. , kramer , c. , rllig , m. 2008 , a&a , submitted draine , b. t. et al .\n, 2007 , apj , 663 , 866 israel , f .\np. ; baas , f. ; rudy , r.j .\n; skillman , e.d . ; woodward , c.e.,2003 , a&a 397,87 jappsen , a .-\nk . ; klessen , r.s . ; glover , s.c.o . ; mac low , m.m . , 2007 , arxiv:0709.3530 nakagawa , t. ; mochizuki , k. ; okuda , h. ; yui , y. y. ; doi , y. ; shibai , h. ; nishimura , t. ; low , f. j. , 1999 , proceedings of star formation 1999 , nagoya , japan madden , s.c . , 2000 , new astronomy reviews , volume 44 , issue 4 - 6 , p. 249\n- 256 madden , s. c. ; galliano , f. ; jones , a. p. ; sauvage , m. , 2006 , a&a , 446 , 877 rllig , m. ; ossenkopf , v. ; jeyakumar , s. ; stutzki , j. ; sternberg , a. , 2006 , a&a , 45 , 917 rllig , m. et al . , 2007 , a&a , 467 , 187 rllig , m. & szczerba , r. , 2008 , in preparation schneider , r. ; ferrara , a. ; natarajan , p. ; omukai , k. , 2002 , apj , 571 , 30 stoerzer , h. ; stutzki , j. ; sternberg , a. , 1996 , a&a , 310 , 592 sternberg , a. ; dalgarno , a. , 1995 , apj , 338 , 197", "role": "user" }, { "content": "almost all properties of a photodissociation region ( pdr ) depend on its metallicity . \n the heating and cooling efficiencies that determine the temperature of the gas and dust , the dust composition , as well as the elemental abundances that influence the chemical structure of the pdr are just three examples that demonstrate the importance of metallicity effects in pdrs . \n pdrs are often associated with sites of star formation . if we want to understand the star formation history of our own galaxy and of distant low - metallicity objects we need to understanding how metallicity acts on pdr physics and chemistry .", "role": "assistant" } ]

[ { "content": "Examine the citation provided below. Determine the primary purpose of this citation within the context of the research paper. \n\nCitation:\n\nThe results are supported by previous studies (Ranjit et al. 2010, Taliaferro et al. 2010, Pearson et al. 2009, Roos et al. 2001, √òverby & Andersen 2000).", "role": "user" }, { "content": "Result", "role": "assistant" } ]

[ { "content": "Examine the text below and extract disease-related entities. Present your findings in a structured JSON format.\n\nYour response should be a JSON object with keys as entity types and values as lists of entities. If no entities are found, return an empty list for that type.\n\nContent:\n\nCharacteristics of intergenerational contractions of the CTG repeat in myotonic dystrophy. In myotonic dystrophy (DM), the size of a CTG repeat in the DM kinase gene generally increases in successive generations with clinical evidence of anticipation. However, there have also been cases with an intergenerational contraction of the repeat. We examined 1, 489 DM parent-offspring pairs, of which 95 (6. 4%) showed such contractions in peripheral blood leukocytes (PBL). In 56 of the 95 pairs, clinical data allowed an analysis of their anticipation status. It is surprising that anticipation occurred in 27 (48%) of these 56 pairs, while none clearly showed a later onset of DM in the symptomatic offspring. The contraction occurred in 76 (10%) of 753 paternal transmissions and in 19 (3%) of 736 maternal transmissions. Anticipation was observed more frequently in maternal (85%) than in paternal (37%) transmissions (P <. 001). The parental repeat size correlated with the size of intergenerational contraction (r2 =. 50, P < <. 001), and the slope of linear regression was steeper in paternal (-. 62) than in maternal (-. 30) transmissions (P < <. 001). Sixteen DM parents had multiple DM offspring with the CTG repeat contractions. This frequency was higher than the frequency expected from the probability of the repeat contractions (6. 4%) and the size of DM sib population (1. 54 DM offspring per DM parent, in 968 DM parents). We conclude that (1) intergenerational contractions of the CTG repeat in leukocyte DNA frequently accompanies apparent anticipation, especially when DM is maternally transmitted, and (2) the paternal origin of the repeat and the presence of the repeat contraction in a sibling increase the probability of the CTG repeat contraction", "role": "user" }, { "content": "{\"Disease\": [\"myotonic dystrophy\", \"DM\"]}", "role": "assistant" } ]

[ { "content": "Examine the abstracts provided from a main scientific article and its cited works. Craft a narrative that synthesizes the key insights and contributions, emphasizing their interconnections. Employ numerical citations such as [1], [2], etc., to reference the cited works.\n\nMain Article Summary:\nPeople can learn a new concept and use it compositionally, understanding how to \"blicket twice\" after learning how to \"blicket.\" In contrast, powerful sequence-to-sequence (seq2seq) neural networks fail such tests of compositionality, especially when composing new concepts together with existing concepts. In this paper, I show that neural networks can be trained to generalize compositionally through meta seq2seq learning. In this approach, models train on a series of seq2seq problems to acquire the compositional skills needed to solve new seq2seq problems. Meta se2seq learning solves several of the SCAN tests for compositional learning and can learn to apply rules to variables.\n\nCited Works Summary:\n[1]: Three years ago, we released the Omniglot dataset for one-shot learning, along with five challenge tasks and a computational model that addresses these tasks. The model was not meant to be the final word on Omniglot; we hoped that the community would build on our work and develop new approaches. In the time since, we have been pleased to see wide adoption of the dataset. There has been notable progress on one-shot classification, but researchers have adopted new splits and procedures that make the task easier. There has been less progress on the other four tasks. We conclude that recent approaches are still far from human-like concept learning on Omniglot, a challenge that requires performing many tasks with a single model.\n\n[2]: A recent approach to few-shot classification called matching networks has demonstrated the benefits of coupling metric learning with a training procedure that mimics test. This approach relies on a complicated fine-tuning procedure and an attention scheme that forms a distribution over all points in the support set, scaling poorly with its size. We propose a more streamlined approach, prototypical networks, that learns a metric space in which few-shot classification can be performed by computing Euclidean distances to prototype representations of each class, rather than individual points. Our method is competitive with state-of-the-art one-shot classification approaches while being much simpler and more scalable with the size of the support set. We empirically demonstrate the performance of our approach on the Omniglot and mini-ImageNet datasets. We further demonstrate that a similar idea can be used for zero-shot learning, where each class is described by a set of attributes, and achieve state-of-the-art results on the Caltech UCSD bird dataset.\n\n[3]: We propose an algorithm for meta-learning that is model-agnostic, in the sense that it is compatible with any model trained with gradient descent and applicable to a variety of different learning problems, including classification, regression, and reinforcement learning. The goal of meta-learning is to train a model on a variety of learning tasks, such that it can solve new learning tasks using only a small number of training samples. In our approach, the parameters of the model are explicitly trained such that a small number of gradient steps with a small amount of training data from a new task will produce good generalization performance on that task. In effect, our method trains the model to be easy to fine-tune. We demonstrate that this approach leads to state-of-the-art performance on two few-shot image classification benchmarks, produces good results on few-shot regression, and accelerates fine-tuning for policy gradient reinforcement learning with neural network policies.\n\n[4]: \n\n[5]: Despite recent breakthroughs in the applications of deep neural networks, one setting that presents a persistent challenge is that of \"one-shot learning.\" Traditional gradient-based networks require a lot of data to learn, often through extensive iterative training. When new data is encountered, the models must inefficiently relearn their parameters to adequately incorporate the new information without catastrophic interference. Architectures with augmented memory capacities, such as Neural Turing Machines (NTMs), offer the ability to quickly encode and retrieve new information, and hence can potentially obviate the downsides of conventional models. Here, we demonstrate the ability of a memory-augmented neural network to rapidly assimilate new data, and leverage this data to make accurate predictions after only a few samples. We also introduce a new method for accessing an external memory that focuses on memory content, unlike previous methods that additionally use memory location-based focusing mechanisms.\n\n[6]: Learning from a few examples remains a key challenge in machine learning. Despite recent advances in important domains such as vision and language, the standard supervised deep learning paradigm does not offer a satisfactory solution for learning new concepts rapidly from little data. In this work, we employ ideas from metric learning based on deep neural features and from recent advances that augment neural networks with external memories. Our framework learns a network that maps a small labelled support set and an unlabelled example to its label, obviating the need for fine-tuning to adapt to new class types. We then define one-shot learning problems on vision (using Omniglot, ImageNet) and language tasks. Our algorithm improves one-shot accuracy on ImageNet from 87.6 to 93.2 and from 88.0 to 93.8 on Omniglot compared to competing approaches. We also demonstrate the usefulness of the same model on language modeling by introducing a one-shot task on the Penn Treebank.", "role": "user" }, { "content": "Meta sequence-to-sequence learning builds on several areas of active research. Meta learning has been successfully applied to few-shot image classification [6] [2] [3] [1] , including tasks that require storing information in an external memory [5] . Few-shot visual tasks are qualitatively different from the compositional, reasoning-based seq2seq tasks studied here, which demand different architectures and learning principles. Closer to the present work, meta learning has been recently applied to low resource machine translation [4] , demonstrating one application of meta learning [3] to seq2seq translation problems. Crucially, these networks tackle a new task through weight updates rather than through memory and reasoning, and it is unclear whether this approach would work for compositional reasoning.", "role": "assistant" } ]

[ { "content": "Consider the following research inquiry and associated key terms. Review the dataset summaries provided and determine which datasets are suitable for addressing the research question. Base your decision on your understanding of machine learning datasets.\nProvide your answer as a JSON list. For example, for the inquiry \"Semi supervised image classification\", a possible response could be: [\"CIFAR-10\", \"CIFAR-100\"]. Ensure the response contains only the dataset names in JSON format.\n\nResearch Inquiry: I want to use a supervised model for pedestrian attribute recognition from images.\n\nKey Terms: pedestrian attribute recognition images\n\nDataset Summaries:\nRAP: The Richly Annotated Pedestrian (RAP) dataset is a dataset for pedestrian attribute recognition. It contains 41,585 images collected from indoor surveillance cameras.\nCompCars: The Comprehensive Cars (CompCars) dataset contains data from two scenarios, including images from web-nature and surveillance-nature. The web-nature data contains 163 car makes with 1,716 car models.\nPETA: The PEdesTrian Attribute dataset (PETA) is a dataset fore recognizing pedestrian attributes, such as gender and clothing style, at a far distance. It is of interest in video surveillance scenarios where face and body close-shots and hardly available.\nPA-100K: PA-100K is a recent-proposed large pedestrian attribute dataset, with 100,000 images in total collected from outdoor surveillance cameras. It is split into 80,000 images for the training set, and 10,000 for the validation set and 10,000 for the test set.\nVisDrone: VisDrone is a large-scale benchmark with carefully annotated ground-truth for various important computer vision tasks, to make vision meet drones. The VisDrone2019 dataset is collected by the AISKYEYE team at Lab of Machine Learning and Data Mining, Tianjin University, China.\n\nDataset Options: A: RAP B: CompCars C: PETA D: PA-100K E: VisDrone", "role": "user" }, { "content": "[\"RAP\", \"PETA\"]", "role": "assistant" } ]

[ { "content": "Read the provided biomedical research paper and create a concise abstract. Ensure the abstract captures the main points of the paper.\n\nFull Paper:\nspondyloarthritis ( spa ) is a group of rheumatic diseases characterized by inflammatory back \n pain , peripheral oligoarthritis , enthesitis , and/or extraarticular manifestations1 . ankylosing spondylitis ( as ) and psoriatic \n arthritis ( psa ) are the most frequently seen spa subtypes in rheumatology units2,3,4 .\nfoot involvement in spa is not uncommon and \n enthesitis , erosive changes , or ankylosis are the main symptoms5 , 6 .\nthis involvement \n may affect foot functions negatively , similar to rheumatoid arthritis ( ra)7 . in rheumatology units , the functional \n states of patients with spa are usually evaluated using bath ankylosing spondylitis \n functional index ( basfi ) or other similar scales globally .\nhowever , these assessments may \n underestimate the foot - related functional limitations in these patients .\nthe foot and ankle outcome score ( faos ) is a scale measuring the foot - related functional \n limitations in the disorders affecting the foot7,8,9,10 .\nit consists of 5 subscales : pain , \n symptoms , activities of daily living ( adl ) , function in sport and recreation ( sport - rec ) , \n and foot and ankle - related quality of life ( qol ) .\nthe turkish version of faos is a valid and \n reliable instrument to assess foot and ankle related problems11 .\nthe aim of this study was to assess specifically the functional limitations caused by foot \n involvement in patients with spa .\npatients with as and psa aged 1870 years , with foot pain for more than 4 weeks who \n underwent anteroposterior ( ap ) and lateral ( l ) feet radiography were included into the \n study .\nthey met the modified new york criteria for as and moll - wright criteria for psa12 , 13 .\npatients who had \n flatfoot , previous foot surgery , or any other foot disorder unrelated to spa , and who had a \n systemic disease such as diabetes or hyperthyroidism were excluded .\nethical approval for \n this study was obtained from the ethical committee of the university where the study was \n conducted .\nthe clinical findings of foot \n involvement were assessed by observing for swelling , redness , or tenderness . to obtain a \n numerical value , a \n( cfs ) was calculated by giving 1 point for \n every finding on one foot [ swelling : 1 point , redness : 1 point , tenderness : 1 point ; the \n maximum cfs score was 6 for the two feet ] .\nthe radiologic involvement of the foot was \n evaluated by the spondyloarthropathy tarsal radiographic index ( spa - tri ) , which is a valid \n and reliable radiologic index developed specifically for the assessment of foot involvement \n in spa , and is suitable for use with two or more x - ray projections .\nit has five points ; 0 : \n normal , 1 : osteopenia or suspicious findings , 2 : definite joint space narrowing , bony \n erosions , periosteal whiskering , enthesophytes , 3 : paraarticular enthesophytes / incomplete \n bridging , 4 : bony ankylosis / joint space fusion or complete bridging .\nthe maximum spa - tri \n score for the two feet ( total spa - tri score ) is 5614 .\nfoot x - ray images were evaluated by a radiologist who had no \n information about the clinical status of subjects .\ntalonavicular , calcaneocuboid , \n intercuneiform , cuneonavicular , and subtalar joints , and the calcaneal attachments of the \n achilles tendon and plantar fascia ( 7 places ) were assessed using the spa - tri .\nthe foot - related functional status of patients was determined by the turkish version of the \n faos .\nfaos is \n calculated by a specific equation , and 100 indicates no problems while 0 indicates \n extreme problems8 .\nsince the pain \n assessment was achieved in detail by faos , no other pain assessment scale was needed .\nc - reactive protein ( crp ) and erythrocyte sedimentation rate ( esr ) were used as serum \n markers for disease activity .\nthirty patients with spa ( 14 as , 16 psa ) with a mean age of 49 years ( range 2670 years ) \n completed the study .\nthe mean faos subscale scores were as follows : pain=58.70 21.75 , \n symptoms=64.88 26.05 , adl=66.27 22.56 , sport - rec=44.33 26.42 , and qol=42.08 24.99 . \n\npain subscale scores correlated positively with adl , sport - rec , and qol subscale scores . \n\nsymptoms subscale score also positively correlated with adl , sport - rec , and qol subscale \n scores ( table 1table 1.positive correlation between pain and symptoms subscale scores with other faos \n subscale scoresadl sport - rec qolsymptomsr0.749 * 0.693 * 0.552*painr0.875 * 0.872 * 0.629*faos : the foot and ankle outcome score , adl : function in daily living , sport - rec : \n functions in sport and recreation , qol : quality of life .\npain and symptoms subscale scores positively correlated with each other ( r : \n 0.679 , p<0.001 ) .\nfaos : the foot and ankle outcome score , adl : function in daily living , sport - rec : \n functions in sport and recreation , qol : quality of life .\nthis value demonstrated that although patients had foot pain , \n they did not have prominent physical examination findings .\nthe mean crp and esr were 1.1 \n ( 0.18.5 ) mg / dl and 32 ( 7100 ) mm / h , respectively , showing low disease activity .\nthere were \n no relationships between faos subscale scores and cfs or serum markers ( crp/ esr ) .\nthe mean spa - tri score was 7.7 ( 024 ) and no correlation was found between faos subscale \n scores and radiologic score .\nfoot disorders may affect mobility and life quality significantly . as frequently involves \n the foot ; the achilles tendon is the second most common site of enthesitis after the \n chondro - sternal junction , and the ankle is the second most common site for peripheral joint \n disease after the knee6 . the involvement \n of the ankle and small joints of the foot is also frequent in psa15 .\nthese effects of as or psa on the foot may lead to \n functional limitations . the functional states and quality of life of patients with spa are \n usually evaluated using questionnaires such as basfi , health assessment questionnaire for \n spondyloarthropathies ( haq - s ) , ankylosing spondylitis quality of life questionnaire ( asqol ) , \n or psa - specific quality of life questionnaire ( psaqol)16,17,18,19 .\nhowever , these \n questionnaires evaluate the functional activities in a global manner without considering the \n specific cause of the limitation . therefore , the functional cost of foot involvement can not \n be assessed clearly with these indices leading to underestimation .\nfaos is a 42-item questionnaire developed for the assessment of functional limitations \n after ankle ligament reconstruction , but it was also used in other disorders affecting the \n foot such as hallux valgus and rheumatoid arthritis7,8,9 .\nit has 5 subscales ; pain , symptoms , adl , sport - rec , and qol .\npain \n subscale include 9 questions evaluating the frequency and severity of pain in certain \n situations such as walking on flat surface or at night while in bed .\nsymptoms subscale has 7 \n questions assessing the stiffness , swelling , and movement properties of the foot / ankle .\nthe \n adl and sport - rec subscales evaluate the degree of difficulty experienced due to foot / ankle \n disorders in functional activities .\nthe fifth subscale , qol , focuses on the awareness of the \n foot / ankle problem8 , 11 .\npain and symptoms subscale scores significantly and positively \n correlated with each other and with adl , sport - rec , and qol subscale scores . pain and \n symptoms such as stiffness or range of motion loss ,\nplain radiography is a routinely used imaging technique in the evaluation of radiologic \n involvement in rheumatic diseases .\nspa - tri is the radiologic index developed specifically \n for the assessment of foot involvement in spa . in this study\nthe mean spa - tri score was 7 , a very low score \n when compared with the maximum score of 56 .\nit could be speculated that although patients \n had symptoms , radiography did not show the involvement clearly , and therefore , no \n statistically significant results were obtained .\nthe magnetic resonance imaging technique is \n quite successful in demonstrating very early changes at the feet even in patients with \n asymptomatic as and psa20 , 21 .\ntherefore , this should be the preferred technique for \n future studies . in this study ,\nthe relationships between the faos subscale scores and cfs and serum markers \n were also assessed .\nthe \n foot is composed of small joints and their examination is relatively difficult than that of \n the large joints .\nthe inflammatory changes producing pain in these small joints may not \n always lead to swelling , redness , or tenderness .\nthese reasons may explain the lack of a \n relationship between cfs and faos subscale scores\n. in our study , crp and esr values were \n distributed in a wide range ( 0.18.5 mg / dl and 7100 mm / h , respectively ) showing that foot \n involvement may not be directly affected from the disease activity .\nthis hypothesis remains \n to be clarified with studies having a larger sample size . in conclusion , rheumatic pain ,\nresulting from the inflammatory changes in the joints and \n related structures , is a very important clinical problem disturbing the mood , sleep , and \n quality of life of patients22,23,24 .\nit is the most \n common presenting symptom of rheumatic diseases of the foot and may precede clinical and \n radiologic findings25 .\nthis study \n demonstrated that foot pain in patients with spa might result in significant foot - related \n functional limitation .\ntherefore , foot involvement and its functional results should be \n evaluated separately regardless of the global functional state and disease activity of the \n patient . to improve pain and function physical therapy modalities or orthosis\nmore studies about the foot involvement at the early and late \n stages of the disease are needed and the possible treatment approaches must be \n investigated .", "role": "user" }, { "content": "[ purpose ] spondyloarthritis is a major inflammatory disease followed - up in the \n rheumatology clinics , foot involvement in spodyloarthritis is common . \n the functional \n states of patients with spondyloarthritis are usually evaluated globally . \n the aim of this \n study was to assess the foot involvement - related functional limitations in patients with \n spondyloarthritis . \n [ subjects and methods ] patients with ankylosing spondylitis and \n psoriatic arthritis with foot pain more than 4 weeks who underwent anteroposterior and \n lateral feet radiography were enrolled into the study . \n a clinical findings score was \n calculated by assigning 1 point for every finding of swelling , redness , and tenderness . \n \n c - reactive protein and erythrocyte sedimentation rate were used as serum markers for \n disease activity . \n foot radiograms were evaluated using the spondyloarthropathy tarsal \n radiographic index and the foot - related functional state of patients was determined by the \n turkish version of the foot and ankle outcome score . [ results ] \n there were no relationships \n between foot and ankle outcome score subscales and clinical findings score , serum markers , \n or radiologic score . \n pain and symptoms subscale scores were result positively correlated \n with activity of daily living , sport and recreation , and quality of life subscale scores . \n \n [ conclusion ] pain and symptoms are the main determinants of foot - related functional \n limitations in spondyloarthritis .", "role": "assistant" } ]

[ { "content": "Examine the following abstract and identify distinct entities. Focus on extracting entities related to participants, interventions, and outcomes.\n\nPresent your findings in a JSON format like: {\"Participant\": [\"example entity\", ...], \"Intervention\": [\"example entity\", ...], \"Outcome\": [\"example entity\", ...]}. If no entities are found for a category, use an empty list.\n\nAbstract Content:\n\nPreliminary evaluation of psychoeducational support interventions on quality of life in rural breast cancer survivors after primary treatment . Although most cancer survivors are at risk for being lost in the transition from treatment to survivorship , rural breast cancer survivors face special challenges that might place them at particular risk . This small-scale preliminary study had 2 specific aims : ( aim 1 ) establish the feasibility of rural breast cancer survivors participation in a longitudinal quality of life ( QOL ) intervention trial and ( aim 2 ) determine the effects of the Breast Cancer Education Intervention ( BCEI ) on overall QOL . Fifty-three rural breast cancer survivors were randomized to either an experimental ( n = 27 ) or a wait-control arm ( n = 26 ) . Participants in the experimental arm received the BCEI consisting of 3 face-to-face education and support sessions and 2 face-to-face and 3 telephone follow-up sessions , along with supplemental written and audiotape materials over a 6-month period . Breast Cancer Education Intervention modules and interventions are organized within a QOL framework . To address the possible effects of attention , wait-control participants received 3 face-to-face sessions and 3 telephone sessions during the first 6 months of participation in the study , but not the BCEI intervention . Research questions addressing aim 1 were as follows : ( a ) can rural breast cancer survivors be recruited into a longitudinal intervention trial , and ( b ) can their participation be retained . Research questions for aim 2 were as follows : ( a ) do participants who received the BCEI show improvement in overall QOL , and ( b ) is the QOL improvement sustained over time . Data were analyzed using repeated-measures general linear mixed models . Results demonstrated the ability to recruit and retain 53 rural breast cancer survivors , that the experimental arm showed improvement in overall QOL ( P = .013 ) , and that there were significant differences in overall QOL between the experimental and wait-control groups at both months 3 and 6 . Thus , it appears that at least some rural breast cancer survivors can and will participate in a larger trial and will maintain their participation and that those that do participate experience significant QOL benefit .", "role": "user" }, { "content": "{\"Intervention\": [\"telephone follow-up sessions\", \"BCEI intervention\", \"longitudinal quality of life ( QOL ) intervention\", \"Breast Cancer Education Intervention modules and interventions\", \"3 face-to-face education and support sessions\", \"Breast Cancer Education Intervention ( BCEI )\", \"psychoeducational support interventions\"], \"Outcome\": [\"overall QOL\", \"quality of life\", \"quality of life ( QOL )\", \"overall QOL .\"], \"Participant\": [\"breast cancer\", \"Fifty-three\"]}", "role": "assistant" } ]

[ { "content": "Explore the following research question and associated terms. Identify the most suitable dataset from the list provided. Use the dataset descriptions to guide your choice.\n\nInquiry: An attempt to demonstrate the ability of CNNs to ignore dynamic objects for the task of pose regression.\n\nKeywords: pose regression images\n\nDataset Information:\nTHEODORE: Recent work about synthetic indoor datasets from perspective views has shown significant improvements of object detection results with Convolutional Neural Networks(CNNs). In this paper, we introduce THEODORE: a novel, large-scale indoor dataset containing 100,000 high- resolution diversified fisheye images with 14 classes.\nSimitate: Simitate is a hybrid benchmarking suite targeting the evaluation of approaches for imitation learning. It consists on a dataset containing 1938 sequences where humans perform daily activities in a realistic environment.\nCOCO: The MS COCO (Microsoft Common Objects in Context) dataset is a large-scale object detection, segmentation, key-point detection, and captioning dataset. The dataset consists of 328K images.\nEgoDexter: The EgoDexter dataset provides both 2D and 3D pose annotations for 4 testing video sequences with 3190 frames. The videos are recorded with body-mounted camera from egocentric viewpoints and contain cluttered backgrounds, fast camera motion, and complex interactions with various objects.\n\nAvailable Datasets: A: THEODORE B: Simitate C: COCO D: EgoDexter", "role": "user" }, { "content": "COCO", "role": "assistant" } ]

[ { "content": "Consider the following research inquiry and associated key terms. Review the dataset summaries provided and determine which datasets are suitable for addressing the research question. Base your decision on your understanding of machine learning datasets.\nProvide your answer as a JSON list. For example, for the inquiry \"Semi supervised image classification\", a possible response could be: [\"CIFAR-10\", \"CIFAR-100\"]. Ensure the response contains only the dataset names in JSON format.\n\nResearch Inquiry: We propose an efficient online multitask tracking framework which jointly learns a deep visual tracker and a multitask\n\nKey Terms: visual tracking video\n\nDataset Summaries:\nMPII: The MPII Human Pose Dataset for single person pose estimation is composed of about 25K images of which 15K are training samples, 3K are validation samples and 7K are testing samples (which labels are withheld by the authors). The images are taken from YouTube videos covering 410 different human activities and the poses are manually annotated with up to 16 body joints.\nSST: The Stanford Sentiment Treebank is a corpus with fully labeled parse trees that allows for a complete analysis of the compositional effects of sentiment in language. The corpus is based on the dataset introduced by Pang and Lee (2005) and consists of 11,855 single sentences extracted from movie reviews.\nMultiNLI: The Multi-Genre Natural Language Inference (MultiNLI) dataset has 433K sentence pairs. Its size and mode of collection are modeled closely like SNLI.\nSICK: The Sentences Involving Compositional Knowledge (SICK) dataset is a dataset for compositional distributional semantics. It includes a large number of sentence pairs that are rich in the lexical, syntactic and semantic phenomena.\nMTL-AQA: A new multitask action quality assessment (AQA) dataset, the largest to date, comprising of more than 1600 diving samples; contains detailed annotations for fine-grained action recognition, commentary generation, and estimating the AQA score. Videos from multiple angles provided wherever available.\nVOT2018: VOT2018 is a dataset for visual object tracking. It consists of 60 challenging videos collected from real-life datasets.\n\nDataset Options: A: MPII B: SST C: MultiNLI D: SICK E: MTL-AQA F: VOT2018", "role": "user" }, { "content": "[\"SST\", \"MultiNLI\", \"SICK\"]", "role": "assistant" } ]

[ { "content": "Analyze the following sentence to identify chemical entities of interest. List these entities in a JSON array format. If no entities are found, return an empty array.\n\nText to Analyze:\n*P<0.05.", "role": "user" }, { "content": "[]", "role": "assistant" } ]

[ { "content": "Review the following segment from a research document in AI. Answer the subsequent query based solely on the provided information. Limit your response to the answer itself.\n\nResearch Segment: Segmentation is a highly relevant task in medical image analysis.Automatic delineation of organs and structures of interest is often necessary to perform tasks such as visual augmentation [10], computer assisted diagnosis [12], interventions [20] and extraction of quantitative indices from images [1].In particular, since diagnostic and interventional imagery often consists of 3D images, being able to perform volumetric segmentations by taking into account the whole volume content at once, has a particular relevance.In this work, we aim to segment prostate MRI volumes. This is a challenging task due to the wide range of appearance the prostate can assume in different scans due to deformations and variations of the intensity distribution. Moreover, MRI volumes are often affected by artefacts and distortions due to field inhomogeneity. Prostate segmentation is nevertheless an important task having clinical relevance both during diagnosis, where the volume of the prostate needs to be assessed [13], and during treatment planning, where the estimate of the anatomical boundary needs to be accurate [4, 20]. The right portion of the network extracts features and expands the spatial support of the lower resolution feature maps in order to gather and assemble the necessary information to output a two channel volumetric segmentation. The two features maps computed by the very last convolutional layer, having 1\\times 1\\times 1 kernel size and producing outputs of the same size as the input volume, are converted to probabilistic segmentations of the foreground and background regions by applying soft-max voxelwise.After each stage of the right portion of the CNN, a de-convolution operation is employed in order increase the size of the inputs (Figure 3) followed by one to three convolutional layers involving half the number of 5\\times 5\\times 5 kernels employed in the previous layer. Similar to the left part of the network, also in this case we resort to learn residual functions in the convolutional stages. The network predictions, which consist of two volumes having the same resolution as the original input data, are processed through a soft-max layer which outputs the probability of each voxel to belong to foreground and to background. In medical volumes such as the ones we are processing in this work, it is not uncommon that the anatomy of interest occupies only a very small region of the scan. This often causes the learning process to get trapped in local minima of the loss function yielding a network whose predictions are strongly biased towards background. As a result the foreground region is often missing or only partially detected. Several previous approaches resorted to loss functions based on sample re-weighting where foreground regions are given more importance than background ones during learning. In this work we propose a novel objective function based on dice coefficient, which is a quantity ranging between 0 and 1 which we aim to maximise. The dice coefficient D between two binary volumes can be written asD=\\frac{2\\sum_{i}^{N}p_{i}g_{i}}{\\sum_{i}^{N}p_{i}^{2}+\\sum_{i}^{N}g_{i}^{2}} A Previously unseen MRI volume can be segmented by processing it in a feed-forward manner through the network. The output of the last convolutional layer, after soft-max, consists of a probability map for background and foreground. The voxels having higher probability (>0.5) to belong to the foreground than to the background are considered part of the anatomy.\n\nInquiry: Why it is needed to have a two channel volumetric segmentation in the output?", "role": "user" }, { "content": "Two channel volumetric segmentation is used at the output to perform binary classification of foreground and background classes using soft-max. Each volume represent the logits for each class at each pixel location.", "role": "assistant" } ]

[ { "content": "Analyze the given paragraph from COVID-19 research. Determine the relevant topics discussed in the text. Your response should be a JSON array containing the identified topics. Ensure the output is a valid JSON array with no additional commentary.\n\nText:\n\nThis statement was released in June 2020 by the Alliance for Academic Internal Medicine to provide guidance for the 2020-2021 residency application cycle in light of the COVID-19 pandemic. While many of the recommendations are specific to this cycle, others, such as the Department Summary Letter of Evaluation, are meant to be an enduring change to the internal medicine residency application process. AAIM realizes that some schools may not yet have the tools or resources to implement the template fully this cycle and look toward collaboration within the internal medicine education community to facilitate adoption in the cycles to come.", "role": "user" }, { "content": "[\"Prevention\"]", "role": "assistant" } ]

[ { "content": "Analyze the provided clinical trial criteria. Identify and extract distinct entities from the text.\n\nReturn the results as a JSON structure. Ensure the output is strictly in JSON format without any additional commentary.\n\nCriteria Text:\n\nChronic HCV Infection of Genotype 1, 4, 5, or 6\nHCV RNA > 103 IU/mL at screening\n18 years of age or older\nDiagnosis of chronic HCV infection, defined as positive HCV antibody or HCV RNA more than 6 months prior to screening OR an assessment of fibrosis F2 or greater prior to screening.\nNYHA Class III: Subjects with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation, dyspnea, or anginal pain.\nNYHA Class IV: Patient with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.\nejection fraction = 30%\nhospitalized for heart failure in last 12 months\nILD criteria: diagnosis of interstitial lung disease with chronic supplemental oxygen requirement at rest and/or with exertion.\nForced expiratory volume (FEV1)< 30% predicted\nOR any FEV1 with chronic supplemental oxygen requirement at rest and/or with exertion\nOR any FEV1 with chronic hypercapnia (baseline partial pressure of arterial carbon dioxide [PaCO2] > 45)", "role": "user" }, { "content": "{\"Condition\": [\"interstitial lung disease\", \"chronic HCV infection\", \"Chronic HCV Infection\", \"heart failure\", \"chronic hypercapnia\"], \"Device\": [], \"Drug\": [], \"Measurement\": [\"HCV antibody\", \"ejection fraction\", \"FEV1\", \"HCV RNA\", \"partial pressure of arterial carbon dioxide\", \"Forced expiratory volume\", \"PaCO2\", \"ILD criteria\", \"NYHA\", \"assessment of fibrosis\"], \"Mood\": [], \"Multiplier\": [], \"Negation\": [], \"Observation\": [\"hospitalized\", \"chronic supplemental oxygen requirement\"], \"Person\": [\"age\"], \"Procedure\": [], \"Qualifier\": [\"Genotype 4\", \"Genotype 1\", \"with exertion\", \"at rest\", \"Genotype 5\", \"Genotype 6\"], \"ReferencePoint\": [\"screening\"], \"Scope\": [\"positive HCV antibody or HCV RNA more than 6 months prior to screening\", \"Genotype 1, 4, 5, or 6\", \"at rest and/or with exertion\"], \"Temporal\": [\"prior to screening\", \"in last 12 months\", \"more than 6 months prior to screening\", \"at screening\"], \"Value\": [\"Class III\", \"positive\", \"Class IV\", \"= 30%\", \"der\\nD years \", \"\\u003e 45\", \"\\u003e 103 IU/mL\", \"\\u003c 30% predicted\", \"F2 or greater\"], \"Visit\": []}", "role": "assistant" } ]

[ { "content": "Transform the following sections from a biomedical study into a simple summary for the general public. Focus on making the information accessible and easy to understand.\n\nResearch Heading: Transcriptional Regulation of Lineage Commitment - A Stochastic Model of Cell Fate Decisions\nContent:\nAbstract:\nMolecular mechanisms employed by individual multipotent cells at the point of lineage commitment remain largely uncharacterized. Current paradigms span from instructive to noise-driven mechanisms. Of considerable interest is also whether commitment involves a limited set of genes or the entire transcriptional program, and to what extent gene expression configures multiple trajectories into commitment. Importantly, the transient nature of the commitment transition confounds the experimental capture of committing cells. We develop a computational framework that simulates stochastic commitment events, and affords mechanistic exploration of the fate transition. We use a combined modeling approach guided by gene expression classifier methods that infers a time-series of stochastic commitment events from experimental growth characteristics and gene expression profiling of individual hematopoietic cells captured immediately before and after commitment. We define putative regulators of commitment and probabilistic rules of transition through machine learning methods, and employ clustering and correlation analyses to interrogate gene regulatory interactions in multipotent cells. Against this background, we develop a Monte Carlo time-series stochastic model of transcription where the parameters governing promoter status, mRNA production and mRNA decay in multipotent cells are fitted to experimental static gene expression distributions. Monte Carlo time is converted to physical time using cell culture kinetic data. Probability of commitment in time is a function of gene expression as defined by a logistic regression model obtained from experimental single-cell expression data. Our approach should be applicable to similar differentiating systems where single cell data is available. Within our system, we identify robust model solutions for the multipotent population within physiologically reasonable values and explore model predictions with regard to molecular scenarios of entry into commitment. The model suggests distinct dependencies of different commitment-associated genes on mRNA dynamics and promoter activity, which globally influence the probability of lineage commitment.\nIntroduction:\nUnderstanding how primary stem and multipotent progenitor cells decide their fate is pivotal in studying mechanisms driving tissue development and maintenance in multicellular organisms. Despite considerable advances in ascribing key genes and regulatory circuits to specific lineages, the diversity of molecular mechanisms employed by individual cells to commit to particular lineage fates remains largely uncharacterized. Recent technical developments in quantitative measurements of single-cell gene expression[1],[2] have revealed stem and progenitor cell populations to be highly heterogeneous, and suggest that individual cells can exhibit transient biases towards different lineages, even in clonal populations[3]–[10]. This molecular heterogeneity may result from stochastic fluctuations caused by noisy gene expression[11], leading to fluctuations in individual mRNA molecule transcription and degradation rates, and likewise for protein production in individual cells[12],[13]. Also, genes switch between active and inactive states, alternating between variable-length transcriptional bursts that can produce a large number of mRNA molecules, and refractory periods in which transcription is significantly reduced[14],[15]. Molecular mechanisms of commitment have been suggested to involve various degrees of gene expression coordination, from activation of a few genes[16] to gradual accumulation of a transcriptome-wide coordinated program[17]. Finally, the role of external cues( e. g. growth factors) in commitment remains unresolved, with a long-standing debate on whether they can instruct cells to commit to a particular fate, or do merely act as survival factors of cells that have committed through intrinsic mechanisms[18],[19]. A considerable hurdle in elucidating these questions is the elusive nature of the lineage commitment transition, which confounds the experimental capture of cells undergoing commitment. Recent advances in microscopy and imaging techniques enabled the tracking of single cells in time[20]. However, the ability of such methods to simultaneously track expression of multiple genes at the single molecule level is still limited, more so for endogenous genes, which may have a role in effecting commitment decisions[2]. Additionally, the molecular heterogeneity of individual committed cells poses a challenge for defining the relative contributions of single regulators, both individually and in combination, to transitions. In this work we follow an integrative approach aiming at computationally modeling the stochastic dynamics of lineage commitment of individual multipotent progenitor cells. We do so using static gene expression profiles of individual self-renewing( SR), erythroid-committed progenitors( CP) and erythroid-differentiated( Ediff) cells, obtained from the bone marrow-derived multipotent hematopoietic cell line EML, for a panel of genes putatively relevant for erythroid and myeloid lineage development( Methods)[21]. We first perform an exploratory analysis of the static gene expression data, which provides insight into relevant features of the multipotent and committed progenitor populations as well as the SR-to-CP transition( Figure 1- top panel): Based upon these results, we implement a novel expansion of the random telegraph model of transcriptional bursting[15],[22] that provides a framework for stochastic commitment as a function of mechanistic aspects of gene expression dynamics( Figure 1- middle panel): This integrative approach is based on, and expands upon, recently published single cell expression data from the hematopoietic EML cell line for populations in the vicinity of the erythroid commitment boundary[21]. We revisit the question of transcriptional program coordination at the outset of lineage specification through correlation analysis and infer putative regulators of the commitment transition. Additionally, we explore the regimens of transcriptional regulation for these genes in the context of a stochastic model of transcriptional bursting and implement expression-dependent rates of commitment which allow the capture of simulated cells at the moment of transition and the assessment of how mechanistic parameters of gene expression regulation impact on the frequency of commitment( Figure 1- bottom panel).\nDiscussion:\nOur stochastic Monte Carlo model approach is to our knowledge novel. It integrates the random telegraph model framework[15],[22] with commitment probabilities obtained from single cell classifiers and cell culture properties. Also, the robust conversion of static expression data, where each data point is considered a “snapshot”, into time series parameters is new in this context. In[38] cell cycle FISH data were analyzed with the same goal using template matching. Our approach, which can be expanded to a larger number of genes and extended to instances where regulatory interactions are present, provides insight into the mechanistic aspects underlying stochastic gene expression and, more importantly, establishes a link between such mechanisms and functional properties of individual cells, by assessing the relevance of promoter and mRNA regulation dynamics in the frequency of commitment. The computational framework was designed and implemented using single cell expression data observations from different populations of the EML hematopoietic cell line[21]. Clustering analyses distinguished cellular sub-compartmentalization from molecular heterogeneity within the CP population and identified subsets of early( CP1) and late( CP2) committed cells, with distinct molecular profiles. Global characterization of CP1 cells revealed a heterogeneous population dispersed in their individual expression profiles, including absence of known erythroid regulators like Gata1, Klf1 or Epor in a significant number of cells. Importantly, we observed only few and weak pairwise correlations between genes in CP1 cells, a pattern that was even more evident amongst SR cells. Hence, no significant level of gene expression coordination is discernible in the commitment transition, at least not within the gene signature analyzed. We proceeded to infer potential key commitment regulators using machine learning methods to separate SR from CP1 cells across the commitment boundary. We identified increase in Gata2 and decrease in Mpo expression as the best predictors of commitment, with changes in a second group of genes, including increase in Gata1 expression, also of some relevance. Although we cannot directly equate predictors of the commitment event with commitment effectors, we have presumed it likely that those genes that best separate SR from CP1 states play a role in their identity or maintenance, and hence may directly effect or report the decision. Also, in exploring mechanisms of commitment, we are aware that our data is exclusively transcriptional and, consequently, mechanistic approaches cannot consider the effects of translational mechanisms and protein quantities. However, protein half-lives for Gata1 and Gata2, for instance, are similar or even shorter than those of their respective mRNAs[36] suggesting that regulation is in fact dominated by transcriptional events. Indeed, short half-lives of both mRNA and proteins seem to be a common feature of genes involved in regulatory mechanisms[39] and partially preclude the existence of buffering effects at the protein level, although they cannot account for all translational regulatory events. A better understanding of the regimens of expression of Gata2, Mpo and Gata1 and their consequences for the SR-to-CP transition could illuminate specific and global mechanisms of lineage commitment. Thus, we explored the dynamics of these three genes by fitting the parameters of a stochastic gene expression model to experimentally observed distributions. These solutions, validated by a local robustness analysis, were taken as strong indicators of the qualitative behavior of the system. We found the genes to have different regulatory dynamics, compatible with global experimental observations in mammalian genes[40]. In the case of Gata1 and to some degree Gata2, the frequency of promoter activity bursts plays a fundamental role; Mpo, on the other hand, is most sensitive to variations in mRNA production times. These patterns are consistent with measurements in yeast, in which transcriptional bursts were more important for larger variations, whereas smaller variations were mostly attributed to transcription-initiation mechanisms[41]. We extended the stochastic model to account for commitment events by means of a logistic regression model that maximizes the separation between SR and CP cells; stochastic commitment events were thus the result of( i) the inherent stochasticity resulting from the mechanistic parameters of Gata1, Gata2 and Mpo regulation, and( ii) the rate of commitment inferred from SR-seeded cell cultures, itself implemented as a random event. Within this framework, the probability of commitment is very low for the vast majority of the time, with infrequent and short transient peaks at high values. This behavior bears some resemblance to excitable systems of differentiation[42]. The extended model allowed us to recreate and capture in silico the moment of commitment. By analyzing the molecular patterns of simulated cells at the transition, we hypothesize that expression of Gata2 defines two states in SR cells: a commitment-impeded state with low Gata2 expression in which no commitment events were observed; and a commitment-permissive state with high Gata2 expression where multiple entry points into commitment can be reached. Given the lack of correlations between the expression of Gata2 and other genes, we could not further explore specific molecular mechanisms by which Gata2 can drive cells into commitment. Nevertheless, we systematically assessed how gradual changes in the stochastic dynamics of gene expression regulation for Gata2, Mpo and Gata1 influence the frequency of commitment. Again, changes in Gata2 regulation had the strongest impact, in particular when perturbing mRNA production and decay. Additionally, we tested the impact of more drastic changes in regulatory parameters, by simulating permanent activity of the Gata1 promoter. The predicted 2-fold increase in frequency of commitment is in agreement with experimental results measuring loss of culture-reconstitution capacity in clonal assays, and is compatible with the reported role of Gata1 in erythroid differentiation and reprogramming experiments[32],[33],[35]. Taken together, these observations bridge mechanisms of gene regulation and functional impact on lineage commitment, and highlight the role of intrinsic noise in cell fate decisions[43]. This integrative approach can also be applied to other differentiating systems, generating hypotheses on transcriptional regulation dynamics and its impact on commitment.", "role": "user" }, { "content": "Stem cells have the capacity to both self-renew and differentiate into specialized cell lineages , thus sustaining tissue formation during embryonic development and permitting tissue homeostasis throughout adult life . Previous studies have suggested that stem cell commitment to a specific lineage may constitute a discrete event of stochastic activation of a small number of key regulator genes . Experimental exploration of this question is challenging , in face of the elusive nature of the commitment transition and due to considerable gene expression heterogeneity between cells . Here , we implement a computational model that simulates gene expression variation through time and affords the capture of in silico commitment events . This model integrates statistical analysis of experimental single-cell gene expression data with dynamical modeling methods to implement a mechanistic framework for stochastic regulation of gene transcription and a probabilistic approach for the commitment rules . Applied to blood cells , our method identifies potential commitment-associated genes , explores how their expression patterns can define alternative commitment regimes , and suggests how differences in regulation of gene expression dynamics can impact the frequency of commitment .", "role": "assistant" } ]

[ { "content": "Transform the following sections from a biomedical study into a simple summary for the general public. Focus on making the information accessible and easy to understand.\n\nResearch Heading: Signature Gene Expression Reveals Novel Clues to the Molecular Mechanisms of Dimorphic Transition in Penicillium marneffei\nContent:\nAbstract:\nSystemic dimorphic fungi cause more than one million new infections each year, ranking them among the significant public health challenges currently encountered. Penicillium marneffei is a systemic dimorphic fungus endemic to Southeast Asia. The temperature-dependent dimorphic phase transition between mycelium and yeast is considered crucial for the pathogenicity and transmission of P. marneffei, but the underlying mechanisms are still poorly understood. Here, we re-sequenced P. marneffei strain PM1 using multiple sequencing platforms and assembled the genome using hybrid genome assembly. We determined gene expression levels using RNA sequencing at the mycelial and yeast phases of P. marneffei, as well as during phase transition. We classified 2, 718 genes with variable expression across conditions into 14 distinct groups, each marked by a signature expression pattern implicated at a certain stage in the dimorphic life cycle. Genes with the same expression patterns tend to be clustered together on the genome, suggesting orchestrated regulations of the transcriptional activities of neighboring genes. Using qRT-PCR, we validated expression levels of all genes in one of clusters highly expressed during the yeast-to-mycelium transition. These included madsA, a gene encoding MADS-box transcription factor whose gene family is exclusively expanded in P. marneffei. Over-expression of madsA drove P. marneffei to undergo mycelial growth at 37°C, a condition that restricts the wild-type in the yeast phase. Furthermore, analyses of signature expression patterns suggested diverse roles of secreted proteins at different developmental stages and the potential importance of non-coding RNAs in mycelium-to-yeast transition. We also showed that RNA structural transition in response to temperature changes may be related to the control of thermal dimorphism. Together, our findings have revealed multiple molecular mechanisms that may underlie the dimorphic transition in P. marneffei, providing a powerful foundation for identifying molecular targets for mechanism-based interventions.\nIntroduction:\nSystemic dimorphic fungi are a group of phylogenetically diverse fungal pathogens which are often geographically restricted but pose an increasing threat to the general population, particularly for immunosuppressed hosts. When transferring between their inhabited environments and human body, morphologic shifts seem necessary for dimorphic fungi to adapt to new circumstance[1]. The phase transitions are regulated by temperature in systemic dimorphic fungi, which take the saprotrophic mycelial form at the lower ambient temperature and the pathogenic yeast form at the higher host body temperature[2]. The mycelium-to-yeast( M-Y) transition is believed to be critical for the pathogenicity of systemic dimorphic fungi because the yeast form is the in vivo cellular form that is capable of evading the host immune system[3], while the yeast-to-mycelium( Y-M) transition is crucial to maintain an environmental reservoir, since these fungi are not directly transmitted between mammalian hosts[4]. Thus, the mechanisms of dimorphism attract great interest within the scientific community[5]. Penicillium marneffei is a strictly thermally dimorphic fungus[6], recently renamed Talaromyces marneffei[7]. At 25°C, P. marneffei grows vegetatively as mycelia and shows typical multinuclear mold morphology. At 37°C, the fungus undergoes the phase transition with concomitant coupling of nuclear and cellular division to form uninucleate, single-celled yeasts. To date, over forty genes have been functionally characterized in P. marneffei( see review[8]), yet genetic mechanisms underlying dimorphism remain elusive. Dimorphic development in P. marneffei is a complex process controlled by a suite of genetic elements. The recent advent of high-throughput approaches has brought new promise for the utilization of genomic and systematic applications to complement the conventional single-gene approaches to identify factors and processes that contribute to dimorphism[9]–[13]. In the present study, we employed next-generation sequencing technologies to revisit the genome sequences of P. marneffei, and systematically identified signature expression changes associated with the dimorphic switch. Specifically, we conducted a hybrid assembly of the P. marneffei genome with data derived from three different sequencing technologies. We also utilized RNA-seq to characterize P. marneffei transcriptomes at various stages of its life cycle. Using the over-expression experiment, we investigated the function of an important transcription factor and showed that the activation of this transcription factor can induce mycelial growth of P. marneffei at 37°C. We provided evidence for the potential roles of secreted proteins, non-coding RNAs, and secondary structural transition of mRNA transcripts in regulating thermal dimorphism in P. marneffei.\nDiscussion:\nWhole-genome sequencing represents a powerful and critical tool for functional genomic studies. Various sequencing technologies have been developed for genome sequencing, but none of them is prefect—all of these technologies have their own advantages and drawbacks. Illumina, for example, delivers high-throughput, inexpensive, and accurate sequence information[35]. However, template amplification is required before sequencing with Illumina, which could cause amplification artifacts[36] and biased coverage[37] related to the chemical-physical properties of the genome. More importantly, Illumina produces short reads, which decreases the continuities of contigs[38]. By contrast, the PacBio sequencer does not require template amplification and thus reduces the composition bias, and is able to produce reads over 10 kb long[39]. These features allow PacBio to bypass the short-read issues of Illumina, and confer the potential advantage to resolve complex repeat regions of the genome. However, the error rate of PacBio reads is as high as 15%[40]. To solve the problem, we used the error correction algorithm to correct as many as possible of the errors in PacBio reads by mapping Illumina reads to them. The Sanger sequencing, representing an earlier generation technology, is still the “gold standard” for validation; however, partially due to the financial considerations, researchers are inclined to use as few Sanger reads as possible. Here, we have set to combine three different generations of sequencing technologies, namely Sanger, Illumina, and PacBio, to produce a better reference P. marneffei genome. The hybrid assembly allowed the advantages of different technologies to complement to each other to improve the quality of assembly. There were more reads that could be mapped to the hybrid assembly of PM1 than the previous one assembled with only Sanger reads[14]. Our results showcased the possibility of improving the overall quality of genome assembly through re-sequencing with diverse platforms. Our strategy is a significant improvement in the balance of cost and genome sequence quality. It is noteworthy that genome sequences of another P. marneffei strain ATCC18224 are available in Genbank( Accession ABAR00000000), which are different from those of P. marneffei strain PM1[14]. Our assembly showed that PM1 may have eight chromosomes because telomere tandem repeat sequences were identified at the ends of 16 scaffolds. In contrast, seven chromosomes are present in the ATCC18224 assembly. A karyotype study also suggested seven chromosomes, but, at the same time, the same study estimated that the genome size was between 25. 7 to 26. 7 Mb[41], which was smaller than the estimates for ATCC18224 and PM1( ∼29. 0 Mb for both). It is possible that a chromosome in size of ca. 2 Mb was overlooked by the karyotype study. Nevertheless, more studies are needed to confirm the number of chromosomes of P. marneffei and reconcile assemblies from different strains in the future. Expression levels at four conditions were considered for each gene as part of the expression pattern analysis. This allowed the multiple-way comparisons of gene expression in all conditions and could, in theory, produce a large number of patterns( i. e., all possible combinations of the results of gene expression level comparison between conditions). To simplify the patterns, we employed the “0”–“1” schema to define signature patterns that only capture the essential differences between conditions. As a result, in the experimental data we collected, only 15 patterns( including “1111” representing equally expressed in all conditions) needed to be considered. This significant reduction of the theoretical number of possible expression-level combinations to the number of observed expression patterns in reality suggested a functional constraint in the biological system of P. marneffei gene expression. We mapped all expression patterns with associated genes onto the different biological stages in the life cycle of P. marneffei( Figure 1). This represents, so far, the most comprehensive expression pattern-based classification of P. marneffei genes. One immediate insight we gain based on the classification was the discovery of expression pattern clusters. Genes in the same cluster have the same expression patterns, probably due to coordinated regulation of these genes that have similar or related functions. The madsA gene is in the cluster of high expression during the morphological transition from the yeast to mycelium form. Indeed, over-expression of this MADS-box gene resulted in the morphological change to mycelium form at 37°C that restricts the wild type P. marneffei in the yeast form. This MADS-box transcription factor is located in the cluster of a series of genes with the same expression patterns. The induced morphological change validated the function of this gene in regulating morphological development. This result also demonstrated the usefulness of the signature expression patterns and the clusters of genes with the same patterns. This concept was further illustrated by a series of discoveries involving secreted proteins, RNA structural transition, and ncRNAs. First, 78. 1% of predicted secreted proteins have expression patterns that are found among the 14 signature patterns. The portion is significantly higher than that of randomly selected genes that have signature expression patterns( P<10−16, Χ2 test). Second, 23. 7%( 14 out of 59) of mRNAs with a highly differential structure at 25 and 37°C have a signature expression pattern. This suggests a widely-spread impact of the mRNA structural transition at different stages of P. marneffei development. Finally, our results describing the expression patterns of ncRNAs and their target genes suggest that ncRNAs may play a role in M-Y transition. In summary, we have made several steps toward a better understanding of P. marneffei thermal dimorphism. Hybrid assembly combined the advantages of different sequencing technologies to improve the quality of genome assembly. Signature expression patterns allowed the prioritization of genes that potentially play important roles in growth regulation and dimorphic development. This strategy was applied to identify the potential master transcription factor, madsA, whose function in regulating yeast-to-mycelium transition was then experimentally validated. We anticipate that our overall strategy and approaches can also be used for studying other systemic fungal pathogens.", "role": "user" }, { "content": "Penicillium marneffei is a significant dimorphic fungal pathogen capable of causing lethal systemic infections . It grows in a yeast-like form at mammalian body temperature and a mold-like form at ambient temperature . The thermal dimorphism of P . marneffei is closely related to its virulence . In the present study , we re-sequenced the genome of P . marneffei using Illumina and PacBio sequencing technologies , and simultaneously assembled these newly sequenced reads in different lengths with previously obtained Sanger sequences . This hybrid assembly greatly improved the quality of the genome sequences . Next , we used RNA-seq to measure the global gene expression of P . marneffei at different phases and during dimorphic phase transitions . We found that 27% of genes showed signature expression patterns , suggesting that these genes function at different stages in the life cycle of P . marneffei . Moreover , genes with same expression patterns tend to be clustered together as neighbors to each other in the genome , suggesting an orchestrated transcriptional regulation for multiple neighboring genes . Over-expression of the MADS-box transcription factor , madsA , located in one of these clusters , confirms the function of this gene in driving the yeast-to-mycelia phase transition irrespective of the temperature cues . Our data also implies diverse roles of secreted proteins and non-coding RNAs in dimorphic transition in P . marneffei .", "role": "assistant" } ]

[ { "content": "Analyze the following sentence to identify chemical entities of interest. List these entities in a JSON array format. If no entities are found, return an empty array.\n\nText to Analyze:\nThewildtypeandmutantmicewerematchedregardingtheirage,weightandsex.", "role": "user" }, { "content": "[]", "role": "assistant" } ]

[ { "content": "Examine the abstracts provided from a main scientific article and its cited works. Craft a narrative that synthesizes the key insights and contributions, emphasizing their interconnections. Employ numerical citations such as [1], [2], etc., to reference the cited works.\n\nMain Article Summary:\nAn @math maximum distance separable (MDS) code has optimal repair access if the minimum number of symbols accessed from @math surviving nodes is achieved, where @math . Existing results show that the sub-packetization @math of an @math high code rate (i.e., @math ) MDS code with optimal repair access is at least @math . In this paper, we propose a class of multi-layer transformed MDS codes such that the sub-packetization is @math , where @math , and the repair access is optimal for any single node. We show that the sub-packetization of the proposed multi-layer transformed MDS codes is strictly less than the existing known lower bound when @math , achieving by restricting the choice of @math specific helper nodes in repairing a failed node. We further propose multi-layer transformed EVENODD codes that have optimal repair access for any single node and lower sub-packetization than the existing binary MDS array codes with optimal repair access for any single node. With our multi-layer transformation, we can design new MDS codes that have the properties of low computational complexity, optimal repair access for any single node, and relatively small sub-packetization, all of which are critical for maintaining the reliability of distributed storage systems.\n\nCited Works Summary:\n[1]: In distributed storage systems, regenerating codes can achieve the optimal tradeoff between storage capacity and repair bandwidth. However, a critical drawback of existing regenerating codes, in general, is the high coding and repair complexity, since the coding and repair processes involve expensive multiplication operations in finite field. In this paper, we present a design framework of regenerating codes, which employ binary addition and bitwise cyclic shift as the elemental operations, named BASIC regenerating codes. The proposed BASIC regenerating codes can be regarded as a concatenated code with the outer code being a binary parity-check code, and the inner code being a regenerating code utilizing the binary parity-check code as the alphabet. We show that the proposed functional-repair BASIC regenerating codes can achieve the fundamental tradeoff curve between the storage and repair bandwidth asymptotically of functional-repair regenerating codes with less computational complexity. Furthermore, we demonstrate that the existing exact-repair product-matrix construction of regenerating codes can be modified to exact-repair BASIC product-matrix regenerating codes with much less encoding, repair, and decoding complexity from the theoretical analysis, and with less encoding time, repair time, and decoding time from the implementation results.\n\n[2]: Maximum distance separable (MDS) codes are optimal error-correcting codes in the sense that they provide the maximum failure tolerance for a given number of parity nodes. Suppose that an MDS code with @math information nodes and @math parity nodes is used to encode data in a distributed storage system. It is known that if @math out of the @math nodes are inaccessible and @math surviving (helper) nodes are used to recover the lost data, then we need to download at least @math fraction of the data stored in each of the helper nodes ( , 2010 and , 2013). If this lower bound is achieved for the repair of any @math erased nodes from any @math helper nodes, we say that the MDS code has the @math -optimal repair property. We study high-rate MDS array codes with the optimal repair property (also known as minimum storage regenerating codes, or MSR codes). Explicit constructions of such codes in the literature are only available for the cases where there are at most three parity nodes, and these existing constructions can only optimally repair a single node failure by accessing all the surviving nodes. In this paper, given any @math and @math , we present two explicit constructions of MDS array codes with the @math -optimal repair property for all @math and @math simultaneously. Codes in the first family can be constructed over any base field @math as long as @math , where @math . The encoding, decoding, repair of failed nodes, and update procedures of these codes all have low complexity. Codes in the second family have the optimal access property and can be constructed over any base field @math as long as @math . Moreover, both code families have the optimal error resilience capability when repairing failed nodes. We also construct several other related families of MDS codes with the optimal repair property.\n\n[3]: We propose a generic transformation that can convert any nonbinary @math maximum distance separable (MDS) code into another @math MDS code over the same field such that: 1) some arbitrarily chosen @math nodes have the optimal repair bandwidth and the optimal rebuilding access; 2) for the remaining @math nodes, the normalized repair bandwidth and the normalized rebuilding access (over the file size) are preserved; and 3) the sub-packetization level is increased only by a factor of @math . Two immediate applications of this generic transformation are then presented. The first application is that we can transform any nonbinary MDS code with the optimal repair bandwidth or the optimal rebuilding access for the systematic nodes only, into a new MDS code which possesses the corresponding repair optimality for all nodes. The second application is that by applying the transformation multiple times, any nonbinary @math scalar MDS code can be converted into an @math MDS code with the optimal repair bandwidth and the optimal rebuilding access for all nodes, or only a subset of nodes, whose sub-packetization level is also optimal.\n\n[4]: An @math maximum distance separable (MDS) array code of length @math , dimension @math , and sub-packetization @math is formed of @math matrices over a finite field @math , with every column of the matrix stored on a separate node in the distributed storage system and viewed as a coordinate of the codeword. Repair of a failed node (recovery of one erased column) can be performed by accessing a set of @math surviving (helper) nodes. The code is said to have the optimal access property if the amount of data accessed at each of the helper nodes meets a lower bound on this quantity. For optimal-access MDS codes with @math , the sub-packetization @math satisfies the bound @math . In our previous work (IEEE Trans. Inf. Theory, vol. 63, no. 4, 2017), for any @math and @math , we presented an explicit construction of optimal-access MDS codes with sub-packetization @math . In this paper, we take up the question of reducing the sub-packetization value @math to make it to approach the lower bound. We construct an explicit family of optimal-access codes with @math , which differs from the optimal value by at most a factor of @math . These codes can be constructed over any finite field @math as long as @math , and afford low-complexity encoding and decoding procedures. We also define a version of the repair problem that bridges the context of regenerating codes and codes with locality constraints (LRC codes), which we call group repair with optimal access . In this variation, we assume that the set of @math nodes is partitioned into @math repair groups of size @math , and require that the amount of accessed data for repair is the smallest possible whenever the @math helper nodes include all the other @math nodes from the same group as the failed node. For this problem, we construct a family of codes with the group optimal access property. These codes can be constructed over any field @math of size @math , and also afford low-complexity encoding and decoding procedures.\n\n[5]: The high repair cost of (n, k) Maximum Distance Separable (MDS) erasure codes has recently motivated a new class of MDS codes, called Repair MDS codes, that can significantly reduce repair bandwidth over conventional MDS codes. In this paper, we describe (n, k, d) Exact-Repair MDS codes, which allow for any failed node to be repaired exactly with access to d survivor nodes, where k ≤ d ≤ n-1. We construct Exact-Repair MDS codes that are optimal in repair bandwidth for the cases of: (α) k n ≤ 1 2 and d ≥ 2k - 11; (b) k ≤ 3. Our codes are deterministic and require a finite-field size of at most 2(n - k). Our constructive codes are based on interference alignment techniques.\n\n[6]: Regenerating codes for distributed storage have attracted much research interest in the past decade. Such codes trade the bandwidth needed to repair a failed node with the overall amount of data stored in the network. Minimum storage regenerating (MSR) codes are an important class of optimal regenerating codes that minimize (first) the amount of data stored per node and (then) the repair bandwidth. Specifically, an @math - @math MSR code @math over @math stores a file @math consisting of @math symbols over @math among @math nodes, each storing @math symbols, in such a way that: 1) the file @math can be recovered by downloading the content of any @math of the @math nodes and 2) the content of any failed node can be reconstructed by accessing any @math of the remaining @math nodes and downloading @math symbols from each of these nodes. In practice, the file @math is typically available in uncoded form on some @math of the @math nodes, known as systematic nodes , and the defining node-repair condition above can be relaxed to requiring the optimal repair bandwidth for systematic nodes only . Such codes are called systematic–repair MSR codes . Unfortunately, finite– @math constructions of @math MSR codes are known only for certain special cases: either low rate, namely @math , or high repair connectivity, namely @math . Our main result in this paper is a finite– @math construction of systematic-repair @math MSR codes for all possible values of parameters @math . We also introduce a generalized construction for @math MSR codes to achieve the optimal repair bandwidth for all values of @math simultaneously.\n\n[7]: Maximum distance separable (MDS) array codes are widely used in storage systems to protect data against erasures. We address the rebuilding ratio problem, namely, in the case of erasures, what is the fraction of the remaining information that needs to be accessed in order to rebuild exactly the lost information? It is clear that when the number of erasures equals the maximum number of erasures that an MDS code can correct, then the rebuilding ratio is 1 (access all the remaining information). However, the interesting and more practical case is when the number of erasures is smaller than the erasure correcting capability of the code. For example, consider an MDS code that can correct two erasures: What is the smallest amount of information that one needs to access in order to correct a single erasure? Previous work showed that the rebuilding ratio is bounded between [1 2] and [3 4]; however, the exact value was left as an open problem. In this paper, we solve this open problem and prove that for the case of a single erasure with a two-erasure correcting code, the rebuilding ratio is [1 2]. In general, we construct a new family of r-erasure correcting MDS array codes that has optimal rebuilding ratio of [1 (r)] in the case of a single erasure. Our array codes have efficient encoding and decoding algorithms (for the cases r=2 and r=3, they use a finite field of size 3 and 4, respectively) and an optimal update property.\n\n[8]: Regenerating codes are a class of distributed storage codes that allow for efficient repair of failed nodes, as compared to traditional erasure codes. An [n, k, d] regenerating code permits the data to be recovered by connecting to any k of the n nodes in the network, while requiring that a failed node be repaired by connecting to any d nodes. The amount of data downloaded for repair is typically much smaller than the size of the source data. Previous constructions of exact-regenerating codes have been confined to the case n=d+1 . In this paper, we present optimal, explicit constructions of (a) Minimum Bandwidth Regenerating (MBR) codes for all values of [n, k, d] and (b) Minimum Storage Regenerating (MSR) codes for all [n, k, d ≥ 2k-2], using a new product-matrix framework. The product-matrix framework is also shown to significantly simplify system operation. To the best of our knowledge, these are the first constructions of exact-regenerating codes that allow the number n of nodes in the network, to be chosen independent of the other parameters. The paper also contains a simpler description, in the product-matrix framework, of a previously constructed MSR code with [n=d+1, k, d ≥ 2k-1].", "role": "user" }, { "content": "Many constructions of MSR codes [8] [1] [5] [7] [3] [6] [2] [4] have been proposed in the literature. For example, product-matrix MSR codes [8] support the parameters that satisfy @math , and are subsequently extended with lower computational complexity [1] . Another construction of MSR codes is based on interference alignment [5] . However, the above two constructions of MSR codes are only suitable for low code rates (i.e, @math ).", "role": "assistant" } ]

[ { "content": "Transform the following sections from a biomedical study into a simple summary for the general public. Focus on making the information accessible and easy to understand.\n\nResearch Heading: Novel Mutations in TARDBP (TDP-43) in Patients with Familial Amyotrophic Lateral Sclerosis\nContent:\nAbstract:\nThe TAR DNA-binding protein 43( TDP-43) has been identified as the major disease protein in amyotrophic lateral sclerosis( ALS) and frontotemporal lobar degeneration with ubiquitin inclusions( FTLD-U), defining a novel class of neurodegenerative conditions: the TDP-43 proteinopathies. The first pathogenic mutations in the gene encoding TDP-43( TARDBP) were recently reported in familial and sporadic ALS patients, supporting a direct role for TDP-43 in neurodegeneration. In this study, we report the identification and functional analyses of two novel and one known mutation in TARDBP that we identified as a result of extensive mutation analyses in a cohort of 296 patients with variable neurodegenerative diseases associated with TDP-43 histopathology. Three different heterozygous missense mutations in exon 6 of TARDBP( p. M337V, p. N345K, and p. I383V) were identified in the analysis of 92 familial ALS patients( 3. 3%), while no mutations were detected in 24 patients with sporadic ALS or 180 patients with other TDP-43–positive neurodegenerative diseases. The presence of p. M337V, p. N345K, and p. I383V was excluded in 825 controls and 652 additional sporadic ALS patients. All three mutations affect highly conserved amino acid residues in the C-terminal part of TDP-43 known to be involved in protein-protein interactions. Biochemical analysis of TDP-43 in ALS patient cell lines revealed a substantial increase in caspase cleaved fragments, including the ∼25 kDa fragment, compared to control cell lines. Our findings support TARDBP mutations as a cause of ALS. Based on the specific C-terminal location of the mutations and the accumulation of a smaller C-terminal fragment, we speculate that TARDBP mutations may cause a toxic gain of function through novel protein interactions or intracellular accumulation of TDP-43 fragments leading to apoptosis.\nIntroduction:\nTransactive response DNA binding protein with a molecular weight of 43 kDa( TDP-43) is a ubiquitously expressed nuclear protein encoded by the TARDBP gene, located on chromosome 1p36. TDP-43 was identified as the major disease accumulated protein in ubiquitinated neuronal cytoplasmic( NCI) and neuronal intranuclear inclusions( NII), that define a growing class of neurological diseases, collectively referred to as TDP-43 proteinopathies[1]–[5]. These diseases include amyotrophic lateral sclerosis( ALS), frontotemporal lobar degeneration( FTLD) with ubiquitin immunoreactive, tau negative inclusions( FTLD-U) and FTLD with motor neuron disease( FTLD-MND). In TDP-43 proteinopathies, TDP-43 is relocated from the nucleus to the cytoplasm and sequestered into inclusions that are mainly composed of hyperphosphorylated and C-terminally truncated TDP-43 fragments[4],[6],[7]. TDP-43 immunoreactive histopathology has also been reported in 20–30% of patients with Alzheimer's disease( AD), 70% of patients with hippocampal sclerosis( HpScl), 33% of patients with Pick's disease and in a subset of patients with Lewy-body related diseases[8]–[12]. TDP-43 is a highly conserved protein, containing 2 RNA recognition motifs and a C-terminal glycine-rich domain, known to promote protein-protein interactions[13]. TDP-43 can bind to the common microsatellite region( GU/GT) n in RNA and DNA, with proposed functions in transcriptional regulation[13]. Most recent research has focused on the role of TDP-43 in the regulation of exon 9 alternative splicing in the cystic fibrosis transmembrane conductance regulator gene, however, additional targets have been identified and others likely await identification[14],[15]. TDP-43 has also been implicated in microRNA biogenesis[16]. ALS and FTLD-U are etiologically complex disorders with genetic as well as environmental factors contributing to the disease. A positive family history is reported in 5–10% of ALS patients and in up to 50% of FTLD-U patients, often with an autosomal dominant pattern of inheritance[17]–[19]. Mutations in the Cu/Zn superoxide dismutase gene( SOD1) account for ∼10–20% of familial and 1–2% of apparent sporadic ALS patients[20]. However, TDP-43 inclusions were not present in SOD1 mutation carriers, suggesting a distinct disease mechanism in these patients[21]. The genetic basis of FTLD-U is just starting to be understood[19]. Loss-of-function mutations in the gene encoding the secreted growth factor progranulin( PGRN) are a major known cause of familial FTLD-U[22],[23], explaining up to 25% of patients worldwide[24]. Other rare genetic causes of familial FTLD-U include mutations in the valosin containing protein gene( VCP) and the gene encoding the charged multivesicular body protein 2B( CHMP2B), while some families with a combination of FTLD and ALS show genetic linkage to a locus on chromosome 9p[25]–[29]. Since rare missense mutations and multiplications have been identified in genes encoding the major constituents of the pathological deposits in several neurodegenerative diseases, we hypothesized that mutations in TARDBP may contribute to the development of TDP-43 proteinopathies. In fact, the first missense mutations in TARDBP were recently discovered in 2 autosomal dominant ALS families and 2 sporadic ALS patients, supporting the central role for TDP-43 in disease pathogenesis[30],[31]. A large population-based study further identified 8 different missense mutations in 3 familial and 6 sporadic ALS patients and showed accumulation of a detergent-insoluble TDP-43 protein product of ∼28 kDa[32]. Here, we report on the extensive mutation screening of TARDBP in a diverse cohort of clinical and pathological confirmed patients with neurodegenerative diseases characterized by TDP-43 pathology, which led to the identification of 3 additional ALS families with TARDBP mutations. We further show accumulation of proteolytic cleaved fragments with a molecular weight of approximately 35 and 25 kDa in lymphoblastoid cell lines derived from TARDBP mutation carriers.\nDiscussion:\nThe identification of rare mutations in genes encoding the major protein component of the pathologic brain depositions observed in familial neurodegenerative diseases has played a critical role in our current understanding of the molecular pathways underlying AD( APP), FTLD( MAPT) and Parkinson's disease( SNCA)[33],[34]. In this study, we performed mutation analyses of TARDBP, encoding TDP-43, in a large cohort of patients with neurodegenerative diseases characterized by TDP-43 pathology to determine if rare mutations or multiplications in TARDBP are involved in the genetic etiology of TDP-43 proteinopathies. Patients with a clinical diagnosis of ALS, FTLD or FTLD-ALS, and patients with pathologically confirmed TDP-43-proteinopathy were included in the analyses. In support of our hypothesis, 14 different pathogenic TARDBP missense mutations were reported by other researchers during the course of this study in familial and sporadic ALS patients[30]–[32],[35]. We identified 2 novel TARDBP missense mutations( p. N345K and p. I383V) and the known p. M337V mutation in 3 out of 92 familial ALS patients( 3. 3%), while no mutations were identified in 24 sporadic ALS patients or 180 patients with other neurodegenerative diseases. p. M337V, p. N345K and p. I383V were excluded in 825 US control individuals and in 652 additional sporadic ALS patients. The TARDBP mutation frequency in our familial ALS cohort is comparable to the frequency reported by Kabashi and colleagues[32]( 3/80 patients = 3. 8%) but considerably higher than the frequency reported by Sreedharan and colleagues( 1/154 patients = 0. 6%)[31]. This may reflect the difference in study design, as a significant number of our patients were index patients of autosomal dominant ALS families, including all 3 patients carrying TARDBP mutations. Unfortunately, since all mutation carriers were index patients obtained from the NINDS Human Genetics Resource Center DNA and Cell Line Repository, DNA of affected relatives was not available to determine segregation of the mutations with disease. The absence of TARDBP mutations in patients with neurodegenerative diseases other than ALS in our study, confirms the lack of mutations and genetic association of TARDBP in FTLD populations[30],[36]–[38]. However, without extensive TARDBP sequence analyses in additional cohorts of FTLD and AD patients, TARDBP mutations cannot be excluded as a rare cause of these disorders. All TARDBP mutation carriers identified in this study presented with probable ALS according to El Escorial criteria in the absence of atypical clinical signs, in agreement with the previous reports on TARDBP mutation carriers. The p. M337V mutation has previously been reported to segregate with disease in a British autosomal dominant ALS family[31]. We identified p. M337V in an index patient from a US family with a strong family history of ALS. Our mutation carrier showed upper limb-onset ALS at 38 years of age, 6 years younger than the earliest onset age reported in the British p. M337V family. Signs of dementia were not reported in any of the family members, consistent with the previous report. An allele sharing study using 12 STR markers flanking TARDBP did not support a common ancestor for the UK family and our US patient, although our set of analyzed markers would not have detected a very distant common ancestor[39],[40]. In addition, we cannot exclude the rare possibility that marker Chr1_11. 28 mutated in patient ND10588 or that the genomic position of this marker is incorrect, which would leave open the possibility of a shared region of maximum 1. 3 Mb( D1S1635-D1S434). In anyway, the identification of p. M337V in two genealogically unrelated ALS families adds further strength to the pathogenicity of TARDBP mutations and justifies mutation screening for TARDBP in patients with familial ALS. Similar to 13 of the 14 previously reported TARDBP mutations, both novel missense mutations identified in this study were located in exon 6 encoding the highly conserved C-terminus of TDP-43, known to be involved in protein-protein interactions( Figure 2). p. N345K was identified in a 43 year old male with a 4 year history of ALS and an autosomal dominant family history. The p. I383V mutation was also identified in a familial ALS patient; however the onset age was 59 years, 2 decades later than the other 2 mutations identified in this study. This may reflect the more conservative amino acid substitution( Iso→Val) or its more C-terminal location in the TDP-43 protein compared to the other mutations, which may induce a different disease mechanism. Alternatively, additional genetic and/or environmental factors may determine the disease expression of TARDBP mutations, as suggested by the wide onset age range( 48–83 years) observed in the recently published family with the p. A315T mutation in TARDBP[30]. Finally, although there is strong evidence supporting that p. N345K and p. I383V are pathogenic, there remains the possibility that these mutations in fact represent rare benign polymorphisms. Definitive confirmation of their pathogenic nature will depend on finding additional ALS patients carrying these mutations. To determine the pathological significance of TARDBP missense mutations on the post-translational processing of TDP-43, we examined human lymphoblastoid cell lines derived from all 3 familial TARDBP mutation carriers identified in this study, 2 ALS patients without TARDBP mutations and 5 control individuals( Figure 3). Patient cell lines revealed a substantial increase in a proteolytic cleaved fragment with a molecular weight of approximately 35 and 25 kDa consistent with caspase cleavage[7]. These data suggest that TARDBP mutations may cause a toxic gain of function through novel protein interactions or intracellular accumulation, particularly of caspase fragments. Kabashi and colleagues previously reported a similar substantial increase in a fragment of approximately 28 kDa in lymphoblastoid cell lines of TARDBP mutation carriers. This fragment accumulated in the presence of a proteasome inhibitor( MG-132), which led the authors to speculate that this TDP-43 product is likely degraded by the ubiquitin-proteasome system( UPS)[32]. While we can't exclude the enhanced aggregation of their mutants in the presence of the inhibitor, our data suggests that proteasome-induced toxicity enhances proteolytic cleavage of TDP-43 into 35 and 25 kDa fragments, resulting in cleavage fragments similar to those observed in ALS patients( Figure 4). Although we can't exclude the possibility that these fragments may be degraded by the UPS, it is likely that the accumulation of these fragments is primarily mediated by caspase cleavage. In conclusion, our findings support that TARDBP mutations are a rare cause of ALS, but so far are not found in other neurodegenerative diseases. Since all reported TARDBP mutations cluster in exon 6 encoding a highly conserved region of the TDP-43 protein, selective mutation analyses of TARDBP exon 6 in familial and sporadic ALS may be warranted.", "role": "user" }, { "content": "The abnormal accumulation of disease proteins in neuronal cells of the brain is a characteristic feature of many neurodegenerative diseases . Rare mutations in the genes that encode the accumulating proteins have been identified in these disorders and are crucial for the development of cell and animal models used to study neurodegeneration . Recently , the TAR DNA-binding protein 43 ( TDP-43 ) was identified as the disease accumulating protein in patients with frontotemporal lobar degeneration with ubiquitin inclusions ( FTLD-U ) and in amyotrophic lateral sclerosis ( ALS ) . TDP-43 was also found in the brains of 20–30% of patients with Alzheimer's disease ( AD ) . Here , we evaluated whether mutations in TDP-43 cause disease in a cohort of 296 patients presenting with FTLD , ALS or AD . We identified three missense mutations in three out of 92 familial ALS patients ( 3 . 3% ) , and no mutations in AD or FTLD patients . All the identified mutations clustered in exon 6 , which codes for a highly conserved region in the C-terminal part of the TDP-43 protein , which is known to be involved in the interaction of TDP-43 with other proteins . We conclude that mutations in TDP-43 are a rare cause of familial ALS , but so far are not found in other neurodegenerative diseases .", "role": "assistant" } ]

[ { "content": "Transform the following sections from a biomedical study into a simple summary for the general public. Focus on making the information accessible and easy to understand.\n\nResearch Heading: Finding driver mutations in cancer: Elucidating the role of background mutational processes\nContent:\nAbstract:\nIdentifying driver mutations in cancer is notoriously difficult. To date, recurrence of a mutation in patients remains one of the most reliable markers of mutation driver status. However, some mutations are more likely to occur than others due to differences in background mutation rates arising from various forms of infidelity of DNA replication and repair machinery, endogenous, and exogenous mutagens. We calculated nucleotide and codon mutability to study the contribution of background processes in shaping the observed mutational spectrum in cancer. We developed and tested probabilistic pan-cancer and cancer-specific models that adjust the number of mutation recurrences in patients by background mutability in order to find mutations which may be under selection in cancer. We showed that mutations with higher mutability values had higher observed recurrence frequency, especially in tumor suppressor genes. This trend was prominent for nonsense and silent mutations or mutations with neutral functional impact. In oncogenes, however, highly recurring mutations were characterized by relatively low mutability, resulting in an inversed U-shaped trend. Mutations not yet observed in any tumor had relatively low mutability values, indicating that background mutability might limit mutation occurrence. We compiled a dataset of missense mutations from 58 genes with experimentally validated functional and transforming impacts from various studies. We found that mutability of driver mutations was lower than that of passengers and consequently adjusting mutation recurrence frequency by mutability significantly improved ranking of mutations and driver mutation prediction. Even though no training on existing data was involved, our approach performed similarly or better to the state-of-the-art methods.\nIntroduction:\nCancer is driven by changes at the nucleotide, gene, chromatin, and cellular levels. Somatic cells may rapidly acquire mutations, one or two orders of magnitude faster than germline cells[1]. The majority of these mutations are largely neutral( passenger mutations) in comparison to a few driver mutations that give cells the selective advantage leading to their proliferation[2]. Such a binary driver-passenger model can be adjusted by taking into account additive pleiotropic effect of mutations[3, 4]. Mutations might have different functional consequences in various cancer types and patients, they can lead to activation or deactivation of proteins and dysregulation of a variety of cellular processes. This gives rise to high mutational, biochemical, and histological intra- and inter-tumor heterogeneity that may explain the resistance to therapies and complicates the identification of driving events in cancer[5, 6]. Point DNA mutations can arise from various forms of infidelity of DNA replication and repair machinery, endogenous, and exogenous mutagens[6–9]. There is an interplay between processes leading to DNA damage and those maintaining genome integrity. The resulting mutation rate can vary throughout the genome by more than two orders of magnitude[10, 11] due to many factors operating on local and global scales[12–14]. Many studies support point mutation rate dependence on the local DNA sequence context for various types of germline and somatic mutations[9, 11, 13, 15]. For both germline and somatic mutations, local DNA sequence context has been identified as a dominant factor explaining the largest proportion of mutation rate variation[10, 16]. Additionally, differences in mutational burden between cancer types suggest tissue type and mutagen exposure as important confounding factors contributing to tumor heterogeneity. Assessing background mutation rate is crucial for identifying significantly mutated genes[17, 18], sub-gene regions[19, 20], mutational hotspots[21, 22], or prioritizing mutations[23]. This is especially important considering that the functional impact of the majority of changes observed in cancer is poorly understood, in particular for rarely mutated genes[24]. Despite this need, there is a persistent lack of quantitative information on per-nucleotide and per-codon background rates in various cancer types and tissues. There are many computational methods that aim to detect driver genes and fewer methods trying to rank mutations with respect to their potential carcinogenicity. As many new approaches to address this issue have been developed[25][26], it still remains an extremely difficult task. As a consequence, many driver mutations, especially in oncogenes, are not annotated as high impact or disease related[27] even though cancer mutations harbor the largest proportion of harmful variants[28]. In this study we utilize probabilistic models that estimate background mutability per nucleotide or codon substitution to rank mutations and help distinguish driver from passenger mutations. The mutability concept has been used in many evolutionary and cancer studies( although it has been estimated in different ways) and is defined as a probability to obtain a nucleotide or codon substitution based on the underlying background processes of mutagenesis and repair that are devoid of cancer selection component affecting a specific genomic( or protein) site. The mutability can be calculated using background models( mutational profiles), mutational signatures or mutations motifs that are constructed under the assumption that vast majority of cancer context-dependent mutations have neutral effects, while only a small number of these mutations in specific sites are under positive or negative selection. To assure this, we removed all recurrent mutations as these mutations might be under selection in cancer. Mutational profiles are calculated by sampling the frequency data on types of mutations and their trinucleotide( for nucleotide mutations) and pentanucleotide( for codon substitutions) contexts regardless of their genomic locations. These models can be used to estimate the expected mutation rate in a given genomic site as a result of different local or long-range context-dependent mutational processes. In this paper we try to decipher the contribution of background DNA mutability in the observed mutational spectrum in cancer for missense, nonsense, and silent mutations. We compiled a set of cancer driver and neutral missense mutations with experimentally validated impacts collected from multiple studies and used this set to verify our approach and compare it with other existing methods. Our approach has been implemented online as part of the MutaGene web-server and as a stand-alone Python package: https://www. ncbi. nlm. nih. gov/research/mutagene/gene.\nDiscussion:\nTo understand what processes drive point mutation accumulation in cancer, we used DNA context-dependent probabilistic models to estimate the baseline mutability for nucleotide mutation or codon substitution in specific genomic sites. Passenger mutations, constituting the majority of all observed mutations, may have largely neutral functional impacts and are unlikely to be under selection pressure. For passenger mutations one would expect that mutations with lower DNA mutability would have lower observed mutational frequency and vice versa. In a recent study the fraction of sites harboring SNPs in the human genome was indeed found to correlate very well with the mutability although the later was estimated differently from our study[39]. We detected a significant positive correlation between background mutability, which is proportional to per-site neutral mutation rate, and observed reoccurrence frequencies of mutations in cancer patients. In accordance with this trend, we also found that mutations that were not observed in cancer cohorts were marked by a lower background mutability. For some genes, such as TP53 or CASP8, mutations and their frequencies can be predicted from their mutability values. Outliers of this association trend, mutations which reoccur at high frequencies but have low mutabilities might be important for inferring mutations under positive selection, as illustrated especially for missense mutations in oncogenes. In this respect, reoccurring synonymous mutations with low mutability may represent interesting cases for further investigation of potential synonymous drivers. Mutability of synonymous mutations was found to be the highest among other types of mutations. Observed mutational frequency of synonymous mutations scales with their mutability, therefore it is important to correct for mutability while ranking these mutations with respect to their driver status. Overall, B-score predicted 102 synonymous driver mutations in 64 out of 520 cancer-associated genes. It has been previously shown that some synonymous mutations might be under positive selection and can affect the speed and accuracy of transcription and translation, protein folding rate, and splicing[40]. Some recurrent highly mutable synonymous mutations might not represent relevant candidates of drivers, whereas some rare mutations with relatively low mutability are predicted to be drivers by our approach( e. g. KDR gene p. Leu355 =, NTRK1 gene p. Asn270 =). In this paper we developed and tested a probabilistic model, implemented as B-Score, to adjust the reoccurrence frequency of a mutation( a measure commonly used in clinical research to identify genes and mutations under selection) by its expected background mutability. B-Score is able to provide a correction to reoccurrence frequency using mutability and improves the classification of cancer driver and passenger mutations by up to 20% compared to reoccurrence frequency alone. The advantages of B-score are that:( i) it is intuitive and interpretable,( ii) does not rely on many parameters, and( iii) does not involve explicit training on driver and passenger mutation sets. One of the disadvantages is that it requires the knowledge of a total number of patients tested. We found that B-Score performed comparably or better to many of state-of-the-art methods even for rare mutations observed in two large cancer cohorts. However, it underperformed for those mutations from combined experimental set that were not observed in cancer patients. These latter mutations might either constitute functionally disruptive mutations not directly connected with the carcinogenesis or might represent rare cancer mutations not yet detected in large cancer cohorts. A lot of efforts have been focused so far on developing a comprehensive set of cancer driver mutations verified at the levels of functional assays or animal models[26, 41, 42]. However, existing sets often contain predictions and very few neutral cancer passenger mutations. The vast majority of computational prediction methods rely on machine learning algorithms trained on mutations from a few genes and/or on recurrent mutations as estimates of driver events or use germline SNPs or silent mutations as the presumed “neutral” set. In many cases, the performance is evaluated on similarly generated synthetic benchmarks. As a result, methods can be trained on incorrectly labeled data and even if trained on correct data, can exhibit a well-known overfitting effect. While mutational processes vary widely among cancer types, and different driver mutations have been shown to be preferentially associated with specific mutational processes[39, 40], there remains a lack of cancer-specific driver/passenger datasets. In our combined dataset, the effects of mutations were determined using experimental assays, which were not linked to any particular cancer type, therefore a pan-cancer model was used for calculation of B-score and other methods tested. However, we provide the ability to apply cancer-specific B-Score ranking of mutations using the models available via the MutaGene package and website( see Methods). Additionally, for some cancer types, the background mutational processes may differ greatly between subsets of cancer patients. For these highly heterogenous cancer types rather than using cancer type specific, it may be more appropriate to use background mutational profiles/models specific for a given cohort. In this study, we restricted our test dataset to only missense mutations that have been experimentally assessed, with several thousands of driver and passenger mutations from 58 genes. Intriguingly, we found that experimentally annotated driver mutations had a lower background mutability than neutral mutations, suggesting possible action of context-dependent codon bias towards less mutable codons at critical sites for these genes, although more studies would have to be conducted to further investigate this observation. This important difference in mutability between drivers and passengers may explain the outstanding performance of the simple measure B-score which enables an understanding of the differential roles that background mutation rate and selection play in shaping the cancer mutational spectrum.", "role": "user" }, { "content": "Cancer development and progression is associated with accumulation of mutations . However , only a small fraction of mutations identified in a patient is responsible for cellular transformations leading to cancer . These so-called drivers characterize molecular profiles of tumors and could be helpful in predicting clinical outcomes for the patients . One of the major problems in cancer research is prioritizing mutations . Recurrence of a mutation in patients remains one of the most reliable markers of its driver status . However , DNA damage and repair processes do not affect the genome uniformly , and some mutations are more likely to occur than others . Moreover , mutational probability ( mutability ) varies with the cancer type . We developed models that adjust the number of mutation recurrences in patients by cancer-type specific background mutability in order to prioritize cancer mutations . Using a comprehensive experimental dataset , we found that mutability of driver mutations was lower than that of passengers , and consequently adjusting mutation recurrence frequency by mutability significantly improved ranking of mutations and driver mutation prediction .", "role": "assistant" } ]

[ { "content": "Evaluate the given public health statement using the provided research abstract. Your goal is to determine the relationship between the claim and the abstract content.\n\n- \"decision\": Indicate whether the abstract \"SUPPORTS\", \"CONTRADICTS\", or provides \"INSUFFICIENT\" information regarding the claim.\n- \"justification\": List sentences from the abstract that back your decision. If the decision is \"INSUFFICIENT\", leave this list empty.\n\nStatement: Your risk of getting very sick from COVID-19 is likely to be lower if your diabetes is well-managed.\n\nResearch Abstract:\nBACKGOUND: To figure out whether diabetes is a risk factor influencing the progression and prognosis of 2019 novel coronavirus disease (COVID-19).\nMETHODS: A total of 174 consecutive patients confirmed with COVID-19 were studied.\nDemographic data, medical history, symptoms and signs, laboratory findings, chest computed tomography (CT) as well the treatment measures were collected and analysed.\nRESULTS: We found that COVID-19 patients without other comorbidities but with diabetes (n = 24) were at higher risk of severe pneumonia, release of tissue injury-related enzymes, excessive uncontrolled inflammation responses and hypercoagulable state associated with dysregulation of glucose metabolism.\nFurthermore, serum levels of inflammation-related biomarkers such as IL-6, C-reactive protein, serum ferritin and coagulation index, D-dimer, were significantly higher (P < .01) in diabetic patients compared with those without, suggesting that patients with diabetes are more susceptible to an inflammatory storm eventually leading to rapid deterioration of COVID-19.\nCONCLUSIONS: Our data support the notion that diabetes should be considered as a risk factor for a rapid progression and bad prognosis of COVID-19.\nMore intensive attention should be paid to patients with diabetes, in case of rapid deterioration.", "role": "user" }, { "content": "{\"verdict\": \"NEI\", \"evidence\": []}", "role": "assistant" } ]

[ { "content": "Examine the provided abstract from a computer science paper. Your objective is to identify and extract relationships between entities. Present these relationships in a structured JSON format.\n\nInput Text:\n\nTwo themes have evolved in speech and text image processing work at Xerox PARC that expand and redefine the role of recognition technology in document-oriented applications. One is the development of systems that provide functionality similar to that of text processors but operate directly on audio and scanned image data. A second, related theme is the use of speech and text-image recognition to retrieve arbitrary, user-specified information from documents with signal content. This paper discusses three research initiatives at PARC that exemplify these themes: a text-image editor -LSB- 1 -RSB-, a wordspotter for voice editing and indexing -LSB- 12 -RSB-, and a decoding framework for scanned-document content retrieval -LSB- 4 -RSB-. The discussion focuses on key concepts embodied in the research that enable novel signal-based document processing functionality.", "role": "user" }, { "content": "[[\"audio and scanned image data\", \"One\", \"USED-FOR\"], [\"recognition technology\", \"document-oriented applications\", \"USED-FOR\"], [\"text-image editor\", \"wordspotter\", \"CONJUNCTION\"], [\"decoding framework\", \"research\", \"HYPONYM-OF\"], [\"wordspotter\", \"voice editing and indexing\", \"CONJUNCTION\"], [\"documents with signal content\", \"speech and text-image recognition\", \"USED-FOR\"], [\"wordspotter\", \"research\", \"HYPONYM-OF\"], [\"One\", \"text processors\", \"CONJUNCTION\"], [\"speech and text-image recognition\", \"theme\", \"USED-FOR\"], [\"decoding framework\", \"scanned-document content retrieval\", \"USED-FOR\"], [\"text-image editor\", \"research\", \"HYPONYM-OF\"], [\"themes\", \"speech and text image processing\", \"PART-OF\"], [\"voice editing and indexing\", \"decoding framework\", \"CONJUNCTION\"]]", "role": "assistant" } ]

[ { "content": "Examine the provided text and determine the interactions between chemical entities and genes. Focus on identifying any connections present.\n\nPresent your findings in a structured JSON format. Each relationship should be represented as an array entry. If no interactions are detected, return an empty array.\n\nText Content:\n\nTopoisomerase IIβ deficiency enhances camptothecin-induced apoptosis. Camptothecin (CPT), a topoisomerase (Top) I-targeting drug that stabilizes Top1-DNA covalent adducts, can induce S-phase-specific cytotoxicity due to the arrest of progressing replication forks. However, CPT-induced non-S-phase cytotoxicity is less well characterized. In this study, we have identified topoisomerase IIβ (Top2β) as a specific determinant for CPT sensitivity, but not for many other cytotoxic agents, in non-S-phase cells. First, quiescent mouse embryonic fibroblasts (MEFs) lacking Top2β were shown to be hypersensitive to CPT with prominent induction of apoptosis. Second, ICRF-187, a Top2 catalytic inhibitor known to deplete Top2β, specifically sensitized MEFs to CPT. To explore the molecular basis for CPT hypersensitivity in Top2β-deficient cells, we found that upon CPT exposure, the RNA polymerase II large subunit (RNAP LS) became progressively depleted, followed by recovery to nearly the original level in wild-type MEFs, whereas RNAP LS remained depleted without recovery in Top2β-deficient cells. Concomitant with the reduction of the RNAP LS level, the p53 protein level was greatly induced. Interestingly, RNAP LS depletion has been well documented to lead to p53-dependent apoptosis. Altogether, our findings support a model in which Top2β deficiency promotes CPT-induced apoptosis in quiescent non-S-phase cells, possibly due to RNAP LS depletion and p53 accumulation.", "role": "user" }, { "content": "[[\"CPT\", \"REGULATOR\", \"Top2\\u03b2\"], [\"CPT\", \"INDIRECT-DOWNREGULATOR\", \"RNAP LS\"], [\"CPT\", \"INDIRECT-DOWNREGULATOR\", \"RNA polymerase II large subunit\"], [\"ICRF-187\", \"INHIBITOR\", \"Top2\\u03b2\"], [\"CPT\", \"REGULATOR\", \"topoisomerase II\\u03b2\"], [\"ICRF-187\", \"INHIBITOR\", \"Top2\"]]", "role": "assistant" } ]

[ { "content": "Examine the following abstract and identify distinct entities. Focus on extracting entities related to participants, interventions, and outcomes.\n\nPresent your findings in a JSON format like: {\"Participant\": [\"example entity\", ...], \"Intervention\": [\"example entity\", ...], \"Outcome\": [\"example entity\", ...]}. If no entities are found for a category, use an empty list.\n\nAbstract Content:\n\nAsthma : communication between hospital and general practitioners . OBJECTIVE To assess whether efforts to actively involve General Practitioners ( GPs ) in the postdischarge care of their paediatric asthma patients improved their satisfaction with communication with hospital staff . METHODOLOGY Randomized controlled trial involving 60 patients admitted to the Royal Children 's Hospital , Melbourne , with acute asthma and an identifiable GP . The GPs of the intervention patients were telephoned during the admission . Intervention patients and their GPs received printed information detailing the care the patient received in hospital and the recommended postdischarge care , as well as standardized educational booklets about asthma . Follow-up appointments were made for intervention patients to attend their GPs . RESULTS The GPs of intervention patients were more satisfied when compared to the GPs receiving a standard level of communication ( 96.4 % vs 48.3 % of the intervention and control GPs , respectively , described the communication as good or extremely good , P = 0.0001 ) . The intervention group GPs believed they were more involved after discharge ( 75.0 % vs 44.8 % , P = 0.005 ) and had greater understanding of their patient 's hospitalisation ( 96.4 % vs 62.1 % , P = 0.005 ) . These differences were noted despite there being no difference in the rate of follow-up attendance with GPs for intervention and control patients ( 85.7 % vs 72.4 % , P = 0.2 ) . Qualitative data supported these findings with GPs expressing approval of the intervention used . CONCLUSION Efforts to actively involve GPs in the postdischarge care of their paediatric patients with asthma resulted in a marked improvement in their satisfaction with the communication with medical staff at the Royal Children 's Hospital , Melbourne . The study had insufficient power to demonstrate a difference in morbidity .", "role": "user" }, { "content": "{\"Intervention\": [\"Follow-up appointments\", \"printed information detailing the care the patient received in hospital and the recommended postdischarge care , as well as standardized educational booklets about asthma\", \"intervention\"], \"Outcome\": [\"satisfied\", \"understanding of their patient \\u0027s hospitalisation\", \"believed they were more involved after discharge\", \"approval of the intervention used\", \"satisfaction with the communication with medical staff\", \"satisfaction with communication with hospital staff\", \"rate of follow-up attendance\"], \"Participant\": [\"acute asthma\", \"general practitioners .\", \"paediatric\"]}", "role": "assistant" } ]

[ { "content": "Review the provided collection of medical RCT summaries. Your objective is to distill the essential insights into a brief conclusion. Focus solely on the synthesis of findings without additional commentary. The RCT summaries are as follows:\n\n\n\nReport Title 1:\nTreatment of hemifacial spasm with botulinum toxin.\nReport Abstract 1:\nThe effectiveness of botulinum toxin injections in 11 patients with hemifacial spasm was investigated in a prospective placebo-controlled blinded study. The patients were treated with four sets of injections to various facial muscles, selected by clinical evaluation. Three injections were with graded doses of toxin and one was with placebo. The order of injections was random and unknown to the patients. Results were scored both subjectively by patient assessment of symptoms and objectively by blinded review of videotapes made one month after each injection. Subjective improvement occurred after 79% of injections with botulinum toxin, regardless of dose of toxin. Only 1 patient improved after placebo. Objective improvement was seen after 84% of injections with botulinum toxin. No patient showed objective improvement after placebo injection. The most frequent side effect was facial weakness, seen after 97% of injections of botulinum toxin. Facial bruising (20%), diplopia (13%), ptosis (7%), and various other mild side effects were seen less frequently. Botulinum toxin appears to be an effective and safe method of therapy for hemifacial spasm.", "role": "user" }, { "content": "The findings of this single eligible trial support the results of large, open, case-control studies showing a benefit rate between 76 and 100%. This effect size probably makes it very difficult to perform new large placebo controlled trials for hemifacial spasm. Despite the paucity of good quality controlled data, all the studies available suggest that BtA is effective and safe for treating hemifacial spasm. Future trials should explore technical factors such as the optimum treatment intervals, different injection techniques, doses, Bt types and formulations. Other issues include service delivery, quality of life, long-term efficacy, safety, and immunogenicity. BtA should be compared with surgical microvascular decompression.", "role": "assistant" } ]

[ { "content": "Examine the following abstract and identify distinct entities. Focus on extracting entities related to participants, interventions, and outcomes.\n\nPresent your findings in a JSON format like: {\"Participant\": [\"example entity\", ...], \"Intervention\": [\"example entity\", ...], \"Outcome\": [\"example entity\", ...]}. If no entities are found for a category, use an empty list.\n\nAbstract Content:\n\n[ Effectiveness of morphine by periarticular injections after shoulder arthroscopy ] . Peripheral opioid receptors have been found in inflamed synovia and the analgesic effect of intra-articularly administered morphine after arthroscopic knee surgery has been proven . There is controversy about efficacy of intraarticular morphine after shoulder arthroscopy . Thirty-two patients with impingement syndrome underwent subacromial decompression in the course of arthroscopic shoulder surgery . At the end of the operation morphine ( 5 mg ) or saline was injected periarticularly . Pain intensity ( rest and passive mobilisation ) was recorded after recovery and after 1,2,4 , and 24 hours ( Numeric Rating Scale ) ; the use of rescue medication ( piritramide by patient controlled analgesia ) was noted . No relevant pain reduction was apparent in the morphine group . Piritramide consumption was identical in both groups ( 19.7 +/- 16 mg vs. 19.8 +/- 19 mg ) . We conclude that periarticularly administered morphine in arthroscopic subacromial decompression in the dosage applied in this study does exert no relevant analgesic effect . This is possibly due to the fact that either subacromial tissue , despite of chronic inflammation , does not show the same reagibility as synovia or it is a problem of the nearly complete resection of the subacromial bursa .", "role": "user" }, { "content": "{\"Intervention\": [\"arthroscopic shoulder surgery\", \"operation morphine ( 5 mg )\", \"piritramide\", \"Piritramide\", \"morphine\", \"saline\"], \"Outcome\": [\"Pain intensity ( rest and passive mobilisation )\", \"patient controlled analgesia\", \"pain reduction\", \"piritramide\", \"Piritramide consumption\", \"rescue medication\", \"analgesic effect\"], \"Participant\": []}", "role": "assistant" } ]

[ { "content": "Analyze the following sentence to identify chemical entities of interest. List these entities in a JSON array format. If no entities are found, return an empty array.\n\nText to Analyze:\nThetransgenicmicedisplayedsignificantlyhigheroxygenconsumptiononthehigh-fatdietthanthecontrollittermates(unpublisheddata).", "role": "user" }, { "content": "[\"oxygen\"]", "role": "assistant" } ]

[ { "content": "Craft a cohesive chapter for a literature review using the abstracts provided. Focus on the chapter's theme, weaving together insights and findings from the abstracts. Highlight key points and note any research gaps.\nLiterature Review Title: Enforcing Security Mechanisms in the IP-Based Internet of Things: An Algorithmic Overview \nChapter Title: Homomorphic Encryption Schemes \n1. Abstract of Cited Paper (BIB001): This paper investigates a novel computational problem, namely the Composite Residuosity Class Problem, and its applications to public-key cryptography. We propose a new trapdoor mechanism and derive from this technique three encryption schemes : a trapdoor permutation and two homomorphic probabilistic encryption schemes computationally comparable to RSA. Our cryptosystems, based on usual modular arithmetics, are provably secure under appropriate assumptions in the standard model.\n\nReview Chapter:", "role": "user" }, { "content": "Homomorphic encryption is a form of encryption that allows specific types of computations to be executed on ciphertexts and obtain an encrypted result that is the ciphertext of the result of operations performed on the plaintext. By denoting E{·} as the homomorphic encryption function and f (·) as the computation function, it holds that: An example of homomorphic encryption is the RSA algorithm. Consider a modulus N and an exponent e. The encryption of a message m is given by E{m} = m e mod N . The homomorphic property holds, since: Other examples of homomorphic encryption schemes are the ECC encryption BIB001 , the ElGamal cryptosystem and the Pailler cryptosystem BIB002 . Homomorphic encryption is receiving a growing interest for application into IoT scenarios, since it could be used to preserve confidentiality among the endpoints of communication, while making it possible for intermediate nodes to be able to process the information without the need to decrypt the data prior to processing. Homomorphic cryptosystems usually require higher computation and need longer keys to achieve a comparable security level than symmetric-key algorithms. Depending on the operation f (·) that can be performed on the encrypted data, the homomorphic encryption scheme can be defined as additive or multiplicative. Additive homomorphism makes it possible to compute sums, subtractions, and scalar multiplication of its operands; multiplicative homomorphism allows to compute the product of its operands. The RSA algorithm is an example of multiplicative homomorphic encryption. An example of additive homomorphic encryption is the Pailler cryptosystem. Given a modulus n, a shared random integer g, and user-generated random integers r 1 and r 2 , the homomorphic property is: Homomorphic encryption schemes that are either additive or multiplicative are denoted as partially homomorphic. If both addition and multiplication are supported, a cryptosystem is denoted as fully homomorphic. Fully homomorphic cryptosystems preserve the ring structure of the plaintexts and, therefore, enable more complex procedures. The investigation for fully homomorphic encryption schemes is still at early stages and no practical scheme has been found with acceptable performance (e.g., in terms of decryption delay). Application to IoT scenarios is a rich research topic.", "role": "assistant" } ]

[ { "content": "Write an abstract for the research paper below. Your response should only include the abstract and no additional text.\n\nArticle text:\nheavy quarks are expected to be a clean and penetrating probe to study the sqgp matter created in heavy ion collisions because of its intrinsic large mass property . by studying interactions between heavy quarks and medium\n, one can learn in detail the flavor dependence of parton energy loss mechanism , and also the medium s degree of thermalization by looking at the medium response to heavy quarks .\nprecision measurements on heavy flavor hadrons in a wide kinematic region will be unique to understand these details .\nfull reconstruction of charm hadrons has significant advantages over semi - leptonic decay leptons because of complete kinematics and clean interpretations .\nquarkonium suppression due to color screening has been originally proposed as a smoking gun for qgp formation .\nbut various cold and hot medium effects complex this story and there hasnt been a direct evidence of color screening so far . bottomonium ( or @xmath0 ) production at rhic may offer us a unique opportunity to directly observe this signature because many cold and hot medium effects ( cold nuclear absorption , regeneration etc . ) are expected to negligible at rhic .\nwhile at lhc , these become complicated , particularly the regeneration process for bottomonium production can be significant , which introduces difficulties in the interpretation .\nin this proceedings , i would like to focus on latest rhic results on charm hadron and quarkonium ( @xmath1 , @xmath0 ) measurements .\nfigure [ fig:1 ] shows the recent star measurements on the charm hadron production cross sections in @xmath2 and minimum bias au+au collisions @xcite .\ncharm hadrons were reconstructed via hadronic decays .\nalthough it was not possible to reconstruct secondary decay vertices for charm hadrons in these measurements , star managed to overcome the large combinatorial background with large amount of statistics .\nthe left plot shows the mid - rapidity production cross sections for @xmath3 and @xmath4 scaled to @xmath5 pairs vs. @xmath6 and the result is compared to a pqcd fonll calculation @xcite .\none can see over a wide @xmath6 region , the measurement is consistent with the upper bound of this fonll calculation .\nan interesting finding is that the charm hadron cross sections measured by cdf @xcite and alice @xcite at higher energies up to 7 tev are also closer to the upper limits of fonll calculations .\nsimilarly , the cross section of non - photonic electrons is also consistent with the upper bound of fonll calculations at @xmath7 1 gev/@xmath8 @xcite .\nthe star @xmath9 meson measurement covers about 70% of total @xmath6 acceptance , leading to a reasonable constrain to the total charm cross section .\n[ fig:1 ] right plot shows the total charm cross section per nucleon - nucleon collisions at mid - rapidity from @xmath2 to central au+au collisions .\nlatest star au+au results were extracted from the @xmath3 spectrum measurements covering @xmath6 from 0.4 up to @xmath10 5 gev/@xmath8 .\nthe @xmath5 cross sections were obtained assuming the @xmath11 fragmentation ratio still holds in au+au collisions which need to be tested in future measurements . the results exhibit an approximate @xmath12 scaling indicating charm quarks are predominantly produced from initial hard scatterings .\nthe @xmath3 spectrum in au+au collisions can be compared to the reference @xmath2 data to calculate the nuclear modification factor @xmath13 .\nfigure [ fig:2 ] left panel shows the recent results from the star measurements .\nthe @xmath13 covers @xmath6 up to @xmath10 5 gev/@xmath8 .\nalthough the values are consistent with unity given current uncertainties , there seems to be a hint of modification for @xmath3 production in this @xmath6 region .\nthe blue dashed line depicts the @xmath13 calculated based on the blast - wave fit to the au+au spectrum .\nif one uses the blast - wave model with light hadron freeze - out parameters and calculates the @xmath13 , the result is shown as shaded area in the plot .\nthe data points are significantly different from this predication indicating the charm hadrons freeze - out differently from the system compared to light hadrons .\nwhen going towards higher @xmath6 , the data points tends to show a slight suppression , however , the uncertainties are large .\nthe right panel of fig .\n[ fig:2 ] plots the @xmath3 @xmath13 from star together with the high @xmath6 measurement from central ( 0 - 20% ) pb+pb collisions by alice @xcite .\none should note the difference in the centrality for these two sets of data points . after considering this\n, there seems to be a consistent trend of @xmath3 @xmath13 between rhic and lhc although the uncertainties need to be shrink for detailed investigation .\none should be aware that @xmath3 @xmath13 less than unity does nt necessarily mean the suppression of charm quark production in heavy ion collisions .\nthe sqgp medium in heavy ion collision may modify the distributions of charm quarks into different charm hadrons compared to @xmath2 collisions because hadronization scheme other than fragmentation ( e.g. coalescence ) can be significant as already been observed for light flavor hadrons .\na complete understanding of charm quark energy loss requires measurements of all ground state charm hadrons in heavy ion collisions .\n@xmath1 production has been reported by the phenix collaboration , focusing on the low @xmath6 suppression observation @xcite . with a couple of subsystem upgrades ,\nstar has been able to measure @xmath1 production with improved statistics , particularly with significant capability covering high @xmath6 up to @xmath10 10 gev/@xmath8 .\na combination of both phenix and star measurements covers significant large acceptance in 4@xmath14 @xcite , offering us a great opportunity to constrain the quarkonium production mechanism as well as to learn the cold and hot medium properties .\nmost newly developed models can produce the cross section data points within accessible kinematic region .\nprecision cross section measurements provide constrains on model calculations . in the meantime , more differential measurements ( e.g. polarization ) and/or with more extended kinematic coverage can allow us to disentangle different models and pin down the quarkonium production mechanism . with significantly improved statistics at high @xmath6 ,\nrhic experiments are now able to study the @xmath6 dependent @xmath1 @xmath13 @xcite .\nfigure [ fig:5 ] shows the @xmath1 @xmath13 results vs. centrality ( left ) and @xmath6 ( right ) . on the left plot ,\nthe latest star au+au results were divided into two @xmath6 bins .\nthe low @xmath6 ( 2 - 5 gev/@xmath8 ) data show consistency with the phenix published data points\n. high @xmath6 ( @xmath15 5 gev/@xmath8 ) data show systematically higher @xmath13 compared to low @xmath6 . in peripheral au+au collisions ,\nthe high @xmath6 data are consistent with no suppression , while in central collisions , @xmath1 s are still significantly suppressed , which may be due to the color - screening effect . on the right , the @xmath13 values are plotted vs. @xmath6 for two centrality bins and one can see the @xmath6 dependent structure more clearly\n. also plotted on these two plots are theoretical model calculations which both include the @xmath1 dissociation in the qgp phase as well as the regeneration process @xcite .\nboth model calculations generally describe the data well .\nthe system size and @xmath6 dependence of @xmath1 @xmath13 can be attributed to the formation time and/or leakage effects .\nthere have been many interesting results from lhc experiments recently .\natlas and cms also observed large suppression of high @xmath6 @xmath1 in central pb+pb collisions @xcite , and the suppression seems to be stronger than that of rhic high @xmath6 @xmath1 s , consistent with more suppression in a larger size system .\nalice reported low @xmath6 @xmath1 @xmath13 at forward rapidity @xcite .\ncomparing to the phenix result , the higher @xmath13 values observed is consistent with more regeneration at lhc than at rhic .\nalthough current observations seem to qualitatively agree with expectations , but quantitatively , we need further systematic studies on both rhic and lhc to understand the quarkonium production mechanism as well as the medium properties .\nthis also requires precision measurements in @xmath16+a collisions to control the shadowing and the cold nuclear absorption effects .\nanother striking result reported by star is the @xmath1 elliptic flow ( @xmath17 ) measurement @xcite .\nit has a significant improvement in term of precision compared the previous phenix measurement @xcite .\nfigure [ fig:6 ] shows the @xmath1 @xmath17 results from both phenix and star in 20 - 60% au+au collisions and they are compared to various model predictions .\ndata show at @xmath18 2 gev/@xmath8 , there is no sizable @xmath17 for @xmath1 , which disfavors coalescence production from thermalized charm quarks .\none should note the valid centrality and @xmath6 regions for this statement .\nbased on model calculations @xcite which generally reproduce the @xmath1 @xmath13 and @xmath17 , the coalescence contribution in 20 - 60% au+au collision at rhic is not dominant , and it mostly contributes in low @xmath6 ( @xmath19 3 gev/@xmath8 ) region .\nhigh @xmath6 region is still dominated by the initial @xmath1 production plus possible dissociation in the medium .\nto get insight of the clean charm quark @xmath17 from the measurement of @xmath1 at rhic energy , one need to focus on the @xmath6 region below @xmath10 3 gev/@xmath8 and central collisions .\nthis requires further improvement in the experimental precision .\nanother alternate way to learn the charm quark @xmath17 will be to measure the charm hadron @xmath17 as experimentally , and it will be achievable with great precision with help of the future silicon vertex detector .\nstudy of bottomonium production at rhic is a unique way to get insight of the originally proposed qgp color screen signature .\nthe challenge for rhic experiments is the statistics which makes this measurement likely to be a multi - year program .\nboth phenix and star have reported @xmath0 ( 1s+2s+3s states if not specified ) signals from @xmath2 and au+au collisions since qm2009 .\nthe star published and phenix preliminary @xmath0 cross sections in @xmath2 collisions are consistent with pqcd model calculations and lie on the trend of energy dependence curve @xcite .\nrecently , with significantly improved statistics in au+au collisions , star was able to measure the centrality dependence of @xmath0 @xmath13 @xcite .\nfigure [ fig:7 ] shows the @xmath0 @xmath13 vs. centrality .\nit shows a trend of @xmath0 suppression in central au+au collisions .\ntaking into account all current uncertainties from au+au and @xmath2 reference , the measured value is @xmath10 3@xmath20 below unity .\nthe red dotted line depicts a naive expectation assuming 2s and 3s states completely melt based on pqcd cross sections and pdg branching ratios .\nthe blue dashed line depicts the expect value when all excited bottomonium states ( including @xmath21 ) all melt and only @xmath0(1s ) survies @xcite .\nthe data now seem to favor the scenario that only @xmath0(1s ) survies , but to learn quantitatively suppression levels of different bottomonium states requires significantly improved statistics in the future . with great mass resolution ,\ncms collaboration was managed to separate ( 2s+3s ) states from 1s state and they reported the separate @xmath13 values in minbias pb+pb collisions at 2.76 tev @xcite . when combining them together to compare with rhic results , the expected\n@xmath13 for central collisions should be less than 0.42 , which is generally in line with the star result .\nhowever , one should note that the cold and hot medium effects may be significantly different between rhic and lhc .\nin a short summary , rhic heavy flavor program has achieved many significant results particularly in the past couple of years .\nit will remain as one of the focuses of rhic heavy ion program in the upcoming rhic ii era .\nboth phenix and star are building significant detector subsystem upgrades now or in the coming years , e.g. phenix vtx and fvtx , star hft and mtd upgrades etc .\nthese are all aiming for precision measurements of both open heavy flavor and quarkonium production at rhic ii . with the lhc experiments ongoing\n, rhic heavy flavor program will be complementary and remain competitive in many aspects\n. some of the measurements will be unique at rhic , including : a ) high precision open charm hadron measurements at low @xmath6 to address charm - medium interactions , b ) bottomonium production measurements as bottomonia are expected to be clean at rhic because of negligible contribution from regeneration , c ) heavy quark correlation measurements as heavy quarks are expected to be back - to - back correlated in @xmath2 collisions which allows clean interpretations for results in heavy ion collisions .\nthese systematic study of heavy flavor measurements at rhic and lhc will significantly improve our understanding of the sqgp matter by quantifying its physical properties with controlled accuracy .", "role": "user" }, { "content": "i review the latest heavy flavor measurements at rhic experiments . measurements from rhic together with preliminary results from lhc offer us an opportunity to systematically study the sqgp medium properties . in the end \n , i will outlook a prospective future on precision heavy flavor measurements with detector upgrades at rhic . \n # 1#2#3#4#1 * # 2 * , # 3 ( # 4 )", "role": "assistant" } ]

[ { "content": "Explore the following research question and associated terms. Identify the most suitable dataset from the list provided. Use the dataset descriptions to guide your choice.\n\nInquiry: The goal of this paper is to introduce a new digital watermarking technology for ownership authorization of deep neural networks\n\nKeywords: intellectual property management images paragraph-level\n\nDataset Information:\nCOVIDx: An open access benchmark dataset comprising of 13,975 CXR images across 13,870 patient cases, with the largest number of publicly available COVID-19 positive cases to the best of the authors' knowledge.\nCIFAR-10: The CIFAR-10 dataset (Canadian Institute for Advanced Research, 10 classes) is a subset of the Tiny Images dataset and consists of 60000 32x32 color images. The images are labelled with one of 10 mutually exclusive classes: airplane, automobile (but not truck or pickup truck), bird, cat, deer, dog, frog, horse, ship, and truck (but not pickup truck).\nDeepWriting: A new dataset of handwritten text with fine-grained annotations at the character level and report results from an initial user evaluation.\nSlashdot: The Slashdot dataset is a relational dataset obtained from Slashdot. Slashdot is a technology-related news website know for its specific user community.\n\nAvailable Datasets: A: COVIDx B: CIFAR-10 C: DeepWriting D: Slashdot", "role": "user" }, { "content": "CIFAR-10", "role": "assistant" } ]

[ { "content": "Analyze the given text to identify specific entities. Focus on extracting relevant data.\n\nProvide your findings in JSON format. Each category should list the entities found.\n\nText:\n\nFrom spots to beads-PTM-peptide bead arrays for the characterization of anti-histone antibodies. Antibodies that recognize PTMs of histones play a central role in epigenetic proteomic research. Modification-specific antibodies are employed in chromatin immunoprecipitation, for Western blotting and during the immunoprecipitation steps for MS-based global proteomic analyses. Knowledge about the antibodies' off-target binding is essential for the interpretation of experimental data. To address this challenge we developed a fast and cost efficient system for generating peptide bead arrays. We employed this method to establish a bead-based peptide array containing 384 peptides displaying phosphorylated, acetylated, methylated, and citrullinated N-terminal regions of histones H2A, H2B, H3 and H4 and controls. We profiled the binding of 40 PTM-specific antibodies important for epigenetic proteomic research.", "role": "user" }, { "content": "{\"Chemical\": [\"N\"]}", "role": "assistant" } ]

[ { "content": "Analyze the provided paragraph from a scientific document. Your goal is to identify and extract relevant entities.\n\nFormat your findings as a JSON object, where each key represents a category of entities, and the corresponding value is a list of entities identified in that category. If no entities are found for a category, return an empty list.\n\nFocus on precision and ensure that the output is strictly in JSON format.\n\nDocument:\n\nExperience of Varied Presentation of Chronic Progressive Disseminated Histoplasmosis in Immunocompetent Patients: A Diagnostic Conundrum We report two cases of chronic progressive disseminated histoplasmosis with unusual and rare clinical picture in a patient with no underlying risk factor. One 50-year-old male, presented with hoarseness of voice, chronic cough, with a history of nonresponding anti-tubercular therapy, revealed mucocutaneous lesions on examination. Fungating vocal cord lesions were visualized on bronchoscopy, raised suspicion of carcinoma. The second case, a 22-year- old female, referred to hospital with suspected vasculitis, with complaints of \"off and on\" fever with decreased oral intake, arthralgia, who later developed generalized nodular skin eruptions. On investigation, human immunodeficiency virus test was found to be negative in both the cases. Histopathological findings of skin biopsy, adrenal and bone marrow aspirates raised suspicion, whereas fungal cultures confirmed Histoplasma infection. Although diagnosis was delayed, but both of them were successfully treated with amphotericin B.", "role": "user" }, { "content": "{\"AnatomicalStructure\": [\"adrenal\"], \"Bacterium\": [], \"BiologicFunction\": [\"suspicion\", \"histoplasmosis\", \"Fungating\", \"vasculitis\", \"carcinoma\", \"nodular skin eruptions\", \"Histoplasma infection\", \"Progressive Disseminated Histoplasmosis\"], \"BiomedicalOccupationOrDiscipline\": [], \"BodySubstance\": [\"bone marrow aspirates\"], \"BodySystem\": [], \"Chemical\": [\"amphotericin B\"], \"ClinicalAttribute\": [\"Immunocompetent\"], \"Eukaryote\": [], \"Finding\": [\"Histopathological findings\", \"decreased oral intake\", \"hoarseness of voice\", \"confirmed\", \"lesions\", \"fever\", \"chronic cough\", \"negative\", \"diagnosis\", \"arthralgia\", \"vocal cord lesions\"], \"Food\": [], \"HealthCareActivity\": [\"bronchoscopy\", \"investigation\", \"human immunodeficiency virus test\", \"treated with\", \"skin biopsy\", \"fungal cultures\"], \"InjuryOrPoisoning\": [], \"IntellectualProduct\": [], \"MedicalDevice\": [], \"Organization\": [\"hospital\"], \"PopulationGroup\": [], \"ProfessionalOrOccupationalGroup\": [], \"ResearchActivity\": [], \"SpatialConcept\": [\"generalized\", \"mucocutaneous\"], \"Virus\": []}", "role": "assistant" } ]

[ { "content": "Transform the following sections from a biomedical study into a simple summary for the general public. Focus on making the information accessible and easy to understand.\n\nResearch Heading: Epidemiologically Optimal Static Networks from Temporal Network Data\nContent:\nAbstract:\nOne of network epidemiology's central assumptions is that the contact structure over which infectious diseases propagate can be represented as a static network. However, contacts are highly dynamic, changing at many time scales. In this paper, we investigate conceptually simple methods to construct static graphs for network epidemiology from temporal contact data. We evaluate these methods on empirical and synthetic model data. For almost all our cases, the network representation that captures most relevant information is a so-called exponential-threshold network. In these, each contact contributes with a weight decreasing exponentially with time, and there is an edge between a pair of vertices if the weight between them exceeds a threshold. Networks of aggregated contacts over an optimally chosen time window perform almost as good as the exponential-threshold networks. On the other hand, networks of accumulated contacts over the entire sampling time, and networks of concurrent partnerships, perform worse. We discuss these observations in the context of the temporal and topological structure of the data sets.\nIntroduction:\nIn the 1980's and 90's, mathematical epidemiology of infectious diseases made great progress. During these years, researchers went from models where every individual meets everyone else with equal probability, to a framework of networks where people are considered as connected if one can infect the other. This new body of theories, network epidemiology[1]–[3], has altered our understanding of disease spreading profoundly. For example, it has changed the concept of epidemic thresholds, outbreak diversity and the role of social networks in intervening infectious disease outbreaks. Furthermore, research in network epidemiology has produced many new techniques to analyze contact data[3],[4], model disease spreading[3],[5],[6], discovering influential spreaders[7]–[9], detecting outbreaks[10]–[12], etc. Network epidemiology rests on coarse simplifications, perhaps the biggest being that that one usually does not explicitly model the dynamic aspects of contact patterns[13]. If we consider two individuals, and assume one of them is infective( infected by a pathogen and able to spread it further), the probability of contagion between the two is in practice not constant in time. The changes in the chance of contagion happens at different time scales—from the order of decades, as people are born and die, to the order of minutes, as they come in and out of range for pathogen transmission. The situation becomes even more complicated if we consider an emerging disease outbreak. First, if we want to apply network epidemiology to control the spreading, we have to predict the future contacts, not just map out the past[9]. Second, the mechanisms behind how and when people make contacts may change from the fact that the people are aware of the epidemics[14],[15]. However, the theory and methods to handle full contact patterns—including both temporal and topological information—is not at all as developed as static network epidemiology. There are for example works presenting mathematical representations for temporal networks and computational studies of the effects of temporal and topological structures( see the survey papers Refs.[16]–[18] and references therein), but the picture they present is far from as complete as the static network epidemiology. For this reason is static networks still an important mathematical modeling framework for epidemiology. To be able to study contact patterns by static methods, one needs to eliminate the temporal dimension. This can be done in many ways, and this paper aims at finding the optimal way. Consider a sequence of contacts—triples( i, j, t) carrying the information about when( assuming a discrete time t) pairs of individuals( i and j) have been in contact. A good static network representation of such a contact sequence should give the same predictions about the disease dynamics as the contact sequence itself. The predictions we focus on in this paper are related to how influential an individual is in the disease spreading. Assuming a disease is introduced in a population by individual i, we compare the expected outbreak size ∑i in a simulation on the contact sequence with a static-network predictors of importance: i's degree ki. The better the performance of the static network predictors, the better is the network representation. The reason we focus on predicting the importance of individuals rather than e. g. the epidemic threshold is that it is less dependent on the parameters of the disease-spreading model. If, for a given set of parameter values, one can predict the total outbreak size but not the important disease spreaders, that is more likely a coincidence than if one can predict the important disease spreaders but not the outbreak size. This is important since, as our main focus is to scan different types of network representations, we will have to limit ourselves to a few parameter values of the disease spreading simulations. In this paper, we will use both empirical and artificially generated temporal-network data sets. We investigate three classes of network representations to find which one that can predict ∑i from ki or ci the best. Furthermore, we investigate how the performance depends on the temporal and topological structures of the data.\nDiscussion:\nWe have explored how to encode as much information from a temporal network and a known start time of an infection into static graphs so that a predictor of disease-spreading importance—degree—is as accurate as possible. The main conclusions are that, on one hand, exponential-threshold networks generally perform best; on the other hand, time-slice networks often perform almost as good. Our general recommendation is thus to use exponential-threshold networks if possible. However, the simplicity in constructing and optimizing a time-slice network makes it a feasible alternative. To straightforwardly use a network of accumulated contacts is not a good idea—for some data sets, the performance is less than 60% of the maximum. In addition, the ongoing networks—recording contacts that are active simultaneously—perform rather poor. The performance is better when there are relatively many concurrent edges, or partnerships,( i. e. when these networks are rather dense), but never as good as the other two methods. It is well established that the overall level of concurrent partnerships increases the frequency of population-wide outbreaks[22],[23], but it seems like, at least in our data sets, the non-concurrent contacts are necessary for determining the importance of individuals in the spreading process. How much do our results generalize beyond our current analysis? There are of course many other ways to evaluate the performance of network representations. Instead of the performance measure that we consider( the ability of a vertex’ degree to predict its rank in a list of estimated sizes of outbreaks originating at that particular vertex), one can imagine other measures. Different types of centrality measures[30]–[32] are candidates for such measures, but these are often global quantities. In practical applications, it is hard to assess quantities other than local—cf. it is easy to check one's degree in an online social network as Facebook, but much harder to know one's value of a global property. Moreover, in many empirical networks, centrality measures( including degree) are strongly correlated in empirical data[33], so we expect our conclusions to remain if we change the static-network importance estimators. In the Supporting Information Table S1, we show that our conclusions are the same if we use a global predictor of importance—coreness[7]. Furthermore, the importance measure for the dynamic simulation can be chosen differently. It measures expected outbreak size if the outbreak starts at the focal vertex. In general, another factor affecting the importance is the chance to acquire the infection. Ideally, an importance measure should weigh together both these aspects. In most types of data, we expect these aspects to be strongly correlated and we settle for the mentioned expected outbreak size. One can also think of other prediction tasks for the comparison than finding influential spreaders—for example, predicting epidemic threshold, peak-time of the epidemics, prevalence as a function of time or the final outbreak size. Such studies would require us to study a specific disease-spreading model for the static network. This added complication is the main reason that we avoid such a direction. However, we also believe( as mentioned above), that predicting influential spreaders is a comparatively easy task. If one cannot say who would be an influential spreader, but still get the epidemic threshold right, the latter seems rather like luck.( Investigating this hypothesis rigorously would be an interesting future direction.) How much do our conclusions depend on the disease simulation model and its parameter values? The per-contact transmission probability probably does not affect the ranking of the vertices( even if the expected outbreak sizes can vary non-linearly). The duration of the infective state, however, could change the ranking. In Ref.[34], the authors find a threshold-like response to changing δ in the Prostitution data, albeit softer than in the other parameter—the transmission probability. If the duration is longer, then we anticipate contacts over a longer time-span to matter. The network representations should of course be adapted to such a change, in the sense that their optimal parameter values would change. It is hard to see why this would change the ranking of the representations, and a preliminary study( investigating the Prostitution data for other δ-values) shows it does not. Other studies[9],[35] also find that qualitative results, like the ranking of influential individuals, are robust to the choice of compartmental model and parameter values. Maybe the most serious reason to be cautious about generalizing our results is that we have investigated only a limited set of temporal-network structures. Indeed one can imagine numerous types of correlations between temporal structure and network position—correlations between edges connected to the same vertex, between vertices connected by an edge, etc. A promising sign, however, is that the empirical data sets span a rather large range of static network structure( both in terms of the network of accumulated contacts and the optimized networks). In the end, it is probably impossible to scan all temporal-network structures. Rather, we hope for higher quality empirical data. This would also allow us to better tailor the network representations to specific pathogens. The ρmax-values—between 0. 68( for the synthetic data) to 0. 93( for the E-mail 2 data)—are, on one hand, rather high( we could predict important spreaders with a quite high confidence). On the other hand, since many goals of network epidemiology( predicting thresholds, etc., as listed above) are more dependent on the details of the contact structure and thus more difficult, we can appreciate the value of having the full, temporal contact patterns. The conclusion from this is to, as long as possible, avoid reducing contact data to static networks[6],[9],[35]–[40]. An interesting question for the future is why some data sets give higher performance values. With the degree sequences of the accumulated networks ρmax is bounded above by about 0. 95–0. 98( 1 is unattainable because of the degeneracy of degrees). The discrepancy comes from the network-construction methods being too blunt to capture the relevant temporal-network structure. On the other side, it may be too much to ask from the method to rank the bulk of peripheral vertices accurately—the difference between them will probably be smaller than the errors in the raw data set. Another open future direction is to design other network representations, perhaps putting different weight depending on burstiness[41] or other temporal traits. It could also be interesting to generalize the study to general spreading phenomena in social networks. This paper finds results also generalize to datasets not directly relevant for infectious disease spreading( the e-mail data), perhaps reflecting strong general patterns in human activity[40],[41].", "role": "user" }, { "content": "To understand how diseases spread in a population , it is important to study the network of people in contact . Many methods to model epidemic outbreaks make the assumption that one can treat this network as static . In reality , we know that contact patterns between people change in time , and old contacts are soon irrelevant—it does not matter that we know Marie Antoinette's lovers to understand the HIV epidemic . This paper investigates methods for constructing networks of people that are as relevant as possible for disease spreading . The most promising method we call exponential-threshold network works by letting contacts contribute less , the further from the beginning of an outbreak they take place . We investigate the methods both on artificial models of the contact patterns and empirical data . Except searching for the optimal network representation , we also investigate how the structure of the original data set affects the performance of the representations .", "role": "assistant" } ]

[ { "content": "Read the provided biomedical research paper and create a concise abstract. Ensure the abstract captures the main points of the paper.\n\nFull Paper:\nthe national tb prevalence survey in eritrea was conducted from february through october 2005 ( 6 ) . in 40 selected villages ,\na census ( which included information about sex and age ) was taken of 875 persons in each village .\nall persons > 15 years of age were asked to provide a morning and a spot sputum sample .\npersons who had 2 positive sputum samples were informed about the test results and referred for treatment .\nthose who had 1 positive sputum sample were referred to a nearby healthcare facility for further smear examination .\nif results of smear examination were negative , thoracic radiographs were taken and evaluated by 2 experienced radiologists . the case definition for a sputum smear positive case was at least 2 sputum specimens positive for acid - fast bacilli by ziehl - neelsen staining and microscopy or at least 1 sputum specimen positive for acid - fast bacilli and radiographic abnormalities consistent with active pulmonary tb ( classification of the national tuberculosis control program in eritrea ) .\nusing the prevalence estimate obtained from the survey and 2 different models , we calculated the cdr for 2004 . in model 1 ,\ndescribed by styblo , cdr = ( notification rate / prevalence rate ) / ( 0.5 + 0.83 [ notification rate / prevalence rate ] ) ( 7,8 ) . in model 2 , described by dye et al .\n, cdr = ( notification rate / prevalence rate ) / ( [ notification rate / prevalence rate ] + 0.5 ) ( 9,10 ) .\nwe then compared the calculated cdr with the cdr estimated by the world health organization ( who ) to evaluate whether comparable conclusions about tb case detection would be obtained .\na total of 38,047 persons were included in the prevalence survey . of those > 15 years of age , 18,152 ( 94.6% ) provided at least 1 sputum sample ( figure ) .\nthe prevalence of new smear - positive tb was estimated at 90/100,000 ( 95% confidence interval [ ci ] 35145/100,000 ) in persons > 15 years of age . in 2005 , 44.7% of\nthe eritrean population was < 15 years of age ( 11 ) , which resulted in an overall new smear - positive tb prevalence of 50/100,000 ( 95% ci 1980/100,000 ) under the assumption of no cases in persons < 15 years of age .\nsummary of tuberculosis prevalence survey in eritrea , 2005 . in 2004 , 17/100,000 new smear - positive cases were reported ( 2 ) .\nfor eritrea , the cdr provided by who is considerably lower than that calculated from the results of the national tb prevalence survey . both estimates indicate that eritrea has not reached the 70% target for case detection . however , the who estimate suggests that the program needs to improve case detection by a factor of 5 , whereas the survey estimate suggests that case detection needs to be improved by a factor of 1.6 .\ntwo explanations may account for the large difference : 1 ) the cdr derived from the tb prevalence survey is too high because of an underestimation of the prevalence of smear - positive tb , or 2 ) the cdr estimate published by who is too low because of an overestimation of the incidence of smear - positive tb . in the national tb prevalence survey , measures were taken to ensure high quality of the results ; e.g. , training of data collectors , repeat census taking , reexamination of all slides found positive on fluorescence microscopy , and reexamination of a 5% random sample of the negative slides .\npersons who had smear - positive tb may have been missed because they did not provide a specimen ; however , because only 5% of eligible persons did not provide a specimen , this can explain only a slight underestimation . furthermore , recorded reasons for not providing a specimen seem to be unrelated to a higher chance of having tb .\nthe quality of the provided specimens may have been suboptimal because instructing and motivating persons to provide a sputum sample is challenging . for diagnosis of tb , microscopic examination of saliva\nis less sensitive than examination of sputum ; however , in 50% of saliva samples from patients with a positive sputum sample , bacilli can be demonstrated ( 12,13 ) . for 27,647 samples that appeared to be saliva , smear \nassuming that only 50% were detected , a maximum of 12 smear - positive tb patients may have been undetected .\ntaking this into account results in a prevalence of 87/100,000 . using this estimate , model 1 provides a cdr of 30% and model 2 a cdr of 28%\nthe possibility that persons who provided a saliva sample were not able to produce a sputum sample because they did not have pathologic pulmonary changes should also be taken into consideration .\nestimation of the incidence of smear - positive tb in eritrea is complicated by the fact that no data from tuberculin or prevalence surveys were available .\nthe only data available for eritrea were reporting data , which experts assessed as being of low quality ( 14 ) .\nuse of this limited information will result in an uncertain incidence estimate , which may result in an unreliable cdr . for most countries in africa ,\nlittle information is available for estimating the prevalence of disease and progress towards the millennium development goals ( http://unstats.un.org/unsd/mi/mi_goals.asp , accessed 2006 aug 30 ) . on the basis of case reporting ,\ntb was rightly declared an emergency by african health ministers at the who africa regional committee in maputo in 2005 ( 15 ) . to be able to fight this emergency , more reliable information about the prevalence of tb in africa is needed .\nfurthermore , for global tb control , reliable information about the tb epidemic in africa is needed because 28% of the incident smear - positive cases occurred in the who african region in 2004 ( 2 ) . in conclusion\n, the example of eritrea shows that a large gap may exist between available estimates of tb prevalence and actual tb prevalence in africa .\nnational tb prevalence surveys in africa would help provide better information on tb prevalence and case detection .", "role": "user" }, { "content": "we used results from a national tuberculosis prevalence survey in eritrea to calculate case detection rate ( cdr ) and compared it with the published cdr . \n the cdr obtained from the survey was 40% , whereas the cdr published by the world health organization was 3 lower ( 14% ) .", "role": "assistant" } ]

[ { "content": "Examine the abstracts provided from a main scientific article and its cited works. Craft a narrative that synthesizes the key insights and contributions, emphasizing their interconnections. Employ numerical citations such as [1], [2], etc., to reference the cited works.\n\nMain Article Summary:\nThe always increasing mobile connectivity affects every aspect of our daily lives, including how and when we keep ourselves informed and consult news media. By studying mobile web data, provided by one of the major Chilean telecommunication companies, we investigate how different cohorts of the population of Santiago De Chile consume news media content through their smartphones. We address the issue of inequalities in the access to information, trying to understand to what extent socio-demographic factors impact the preferences and habits of the users.\n\nCited Works Summary:\n[1]: CONICYT 63130228 Movistar - Telefonica Chile Chilean government initiative CORFO 13CEE2-21592 (2013-21592-1-INNOVA PRODUCCION2013-21592-1) Conicyt's Proyecto de Informacion Cientifica, Pluralismo en el Sistema Informativo Nacional PLU140001 Millenium Institute for Foundational Research on Data\n\n[2]: \n\n[3]: News consumers expect news outlets to be objective and balanced in their reports of events and opinions. However, there is a growing body of evidence of bias in the media caused by underlying political and socio-economic viewpoints. Previous studies have tried to classify the partiality of the media, but there is little work on quantifying it, and less still on the nature of this partiality. The vast amount of content published in social media enables us to quantify the inclination of the press to pre-defined sides of the socio-political spectrum. To describe such tendencies, we use tweets to automatically compute a news outlet’s political and socio-economic orientation. Results show that the media have a measurable bias, and illustrate this by showing the favoritism of Chilean media for the ruling political parties in the country. This favoritism becomes clearer as we empirically observe a shift in the position of the mass media when there is a change in government. Even though relative differences in bias between news outlets can be observed, public awareness of the bias of the media landscape as a whole appears to be limited by the political space defined by the news that we receive as a population. We found that the nature of the bias is reflected in the vocabulary used and the entities mentioned by different news outlets. A survey conducted among news consumers confirms that media bias has an impact on the coverage of controversial topics and that this is perceivable by the general audience. Having a more accurate method to measure and characterize media bias will help readers position outlets in the socio-economic landscape, even when a (sometimes opposite) self-declared position is stated. This will empower readers to better reflect on the content provided by their news outlets of choice.", "role": "user" }, { "content": "Chilean news media have been studied to outline for example their ownership structures or their political bias and to understand the effects of certain press manipulations by owners of content shown [1] . These results are based on hypotheses born out of an operationalization of Herman and Chomsky's Propaganda Model [2] , whose so-called filters'' provide an assessment of how the media behave. One particular hypothesis is that the media will manipulate content to target news to appeal to a certain audience. This has been explored also using Twitter data [3] . What we study here is a specialization of that study; namely, how people of different socio-economic backgrounds access news media information using their mobile phones, also with an insight on particular news outlets, at the finest possible level of granularity.", "role": "assistant" } ]

[ { "content": "Analyze the provided text excerpt from a scientific document. Identify and extract distinct entities based on predefined categories.\n\nDeliver the results as a JSON structure where each key represents an entity category, and the associated value is a list of identified entities. If no entities are found for a category, return an empty list.\n\nText Excerpt:\n\nPhospholipase C gamma 1 overexpression and activation induced by interferon beta in human T lymphocytes: an ISGF3-independent response. Interferons exert their antiviral, antiproliferative and immunoregulatory activities by stimulating the expression of several genes. Such genes disclose a common element within their promoters, defined Interferon Stimulated Response Element (ISRE), which binds a nuclear factor (s) translocated from the cytoplasm to the nucleus (ISGF3) after the binding of interferon (IFN) to the specific receptor. Here we report the induction of the synthesis and of the hydrolytic activity of phospholipase C gamma 1 (PLC gamma 1) in human T lymphocytes by IFN-beta. The increased level of PLC gamma 1 becomes evident after 90 min of IFN-beta treatment and is still detectable after 24 h. Neither the PLC gamma 1 overexpression induced by IFN nor the increased hydrolytic activity of the enzyme appear to be affected by pretreatment of the cells with the protein tyrosine kinase inhibitor genistein, which is known to prevent the association of ISGF3 components. These results suggest that in human T lymphocytes IFN-beta can activate other transcription factor (s) distinct from ISGF3 to regulate PLC gamma 1 expression. In addition, the ability of this enzyme to hydrolyse PIP2, also in the presence of genistein, implies the possibility that this enzyme can exert its hydrolytic activity independently of protein tyrosine kinase activation.", "role": "user" }, { "content": "{\"CellLine\": [], \"CellType\": [\"human T lymphocytes\", \"the cells\"], \"DNA\": [\"promoters\", \"ISRE\", \"Interferon Stimulated Response Element\"], \"Protein\": [\"tyrosine kinase\", \"enzyme\", \"phospholipase C gamma 1\", \"ISGF3\", \"IFN - beta\", \"Phospholipase C gamma 1\", \"interferon (IFN)\", \"IFN\", \"PLC gamma 1\", \"nuclear factor\", \"Interferons\", \"interferon\", \"transcription factor\", \"immunoregulatory\", \"protein tyrosine kinase\", \"interferon beta\"], \"RNA\": []}", "role": "assistant" } ]

[ { "content": "Evaluate the given public health statement using the provided research abstract. Your goal is to determine the relationship between the claim and the abstract content.\n\n- \"decision\": Indicate whether the abstract \"SUPPORTS\", \"CONTRADICTS\", or provides \"INSUFFICIENT\" information regarding the claim.\n- \"justification\": List sentences from the abstract that back your decision. If the decision is \"INSUFFICIENT\", leave this list empty.\n\nStatement: A major difference between the flu and COVID-19 is that the former has both preventative and curative treatments, and the latter does not.\n\nResearch Abstract:\nBackground The outbreak of coronavirus disease 2019 (COVID-19) in December 2019 overlaps with the flu season.\nMethods We compared clinical and laboratory results from 719 influenza and 973 COVID-19 patients from January to April 2020.\nWe compiled laboratory results from the first 14 days of the hospitalized patients using parameters that are most significantly different between COVID-19 and influenza and hierarchically clustered COVID-19 patients based on these data.\nThe clinical outcomes were compared among different clusters.\nResults Temporal analyses of laboratory results revealed that compared to influenza, patients with COVID-19 exhibited a continued increase in the white blood cell count, rapid decline of hemoglobin, more rapid increase in blood urea nitrogen (BUN) and D-dimer, and higher level of alanine transaminase, C-reactive protein, ferritin, and fibrinogen.\nUsing these results, we sub-classified the COVID-19 patients into 5 clusters through a hierarchical clustering analysis.\nWe then reviewed the medical record of these patients and risk stratified them based on the clinical outcomes.\nThe cluster with the highest risk showed 27.8% fatality, 94% ICU admission, 94% intubation, and 28% discharge rates compared to 0%, 38%, 22%, and 88% in the lowest risk cluster, respectively.\nPatients in the highest risk cluster had leukocytosis including neutrophilia and monocytosis, severe anemia, higher BUN, creatinine, D-dimer, alkaline phosphatase, bilirubin, and troponin.\nConclusions There are significant differences in the clinical and laboratory courses between COVID-19 and influenza.\nRisk stratification in hospitalized COVID-19 patients using laboratory data could be useful to predict clinical outcomes and pathophysiology of these patients.", "role": "user" }, { "content": "{\"verdict\": \"NEI\", \"evidence\": []}", "role": "assistant" } ]

[ { "content": "Analyze the provided text excerpt from a scientific document. Identify and extract distinct entities based on predefined categories.\n\nDeliver the results as a JSON structure where each key represents an entity category, and the associated value is a list of identified entities. If no entities are found for a category, return an empty list.\n\nText Excerpt:\n\nConstruction and biological characterization of an interleukin-12 fusion protein (Flexi-12): delivery to acute myeloid leukemic blasts using adeno-associated virus. Interleukin-12 (IL-12) is a cytokine that exhibits pleiotropic effects on lymphocytes and natural killer cells and has been shown to have promise for the immunotherapy of cancer. The combination of the immune costimulatory molecule B7. 1 and IL-12 has been shown to be synergistic for T cell activation. By transfecting tumor cells with both IL-12 and B7. 1 cDNAs, it may be possible to use these modified targets as vaccines. A major obstacle in designing a vector to deliver these genes results from the structure of IL-12. Functional IL-12 is a heterodimer composed of two distinct subunits that are encoded by separate genes on different chromosomes. Production of functional IL-12 requires the coordinated expression of both genes. This presents several problems in vectors, particularly those in which additional genes, either a co-stimulatory gene or a selectable marker, are inserted. Therefore, we have constructed a single cDNA that encodes a single-chain protein, called Flexi-12, which retains all of the biological characteristics of recombinant IL-12 (rIL-12). The monomeric polypeptide Flexi-12 is able to induce the proliferation of phytohemagglutinin (PHA) blasts, induce PHA blasts to secrete interferon-gamma (IFN-gamma) and additionally, by preincubation, enhance the killing of K562 targets by PBLs. These phenomena are in a dose-dependent manner comparable to that seen with rIL-12. We have also shown that tyrosine phosphorylation of the STAT 4 transcription factor, which has been shown to be unique to the IL-12 signaling pathway, occurs with Flexi-12 at levels similar to those seen with rIL-12. We have packaged Flexi-12 into a recombinant adeno-associated virus (AAV) and used this vector to infect acute myeloid leukemic (AML) blasts. Infected AML blasts produced between 2 and 6 ng of IL-12 / 10 (6) cells per ml per 48 hr. These studies also confirm that AAV is an efficient delivery vehicle for cytokines to leukemic cells. Direct analysis of these modified cells acting as tumor vaccines is underway.", "role": "user" }, { "content": "{\"CellLine\": [\"phytohemagglutinin (PHA) blasts\", \"PHA blasts\"], \"CellType\": [\"lymphocytes\", \"PBLs\", \"acute myeloid leukemic (AML) blasts\", \"acute myeloid leukemic blasts\", \"natural killer cells\", \"AML blasts\"], \"DNA\": [\"IL - 12 and B7 . 1 cDNAs\", \"cDNA\", \"co - stimulatory gene\"], \"Protein\": [\"interferon - gamma\", \"Flexi - 12\", \"IFN - gamma\", \"phytohemagglutinin\", \"PHA\", \"cytokine\", \"single - chain protein\", \"Interleukin - 12\", \"immune costimulatory molecule\", \"rIL - 12\", \"IL - 12\", \"B7 . 1\", \"heterodimer\", \"functional IL - 12\", \"cytokines\", \"interleukin - 12 fusion protein\", \"STAT 4 transcription factor\"], \"RNA\": []}", "role": "assistant" } ]

[ { "content": "Analyze the following sentence to identify chemical entities of interest. List these entities in a JSON array format. If no entities are found, return an empty array.\n\nText to Analyze:\nTofacilitatethefunctionalstudyofthisnovelgenefamily,wehaveclonedandcharacterizedAcdp,themousehomologueofthehumanACDPgenefamily.", "role": "user" }, { "content": "[]", "role": "assistant" } ]

[ { "content": "Analyze the following sentence to identify chemical entities of interest. List these entities in a JSON array format. If no entities are found, return an empty array.\n\nText to Analyze:\nMembranetraffickingandmitochondrialabnormalitiesprecedesubunitcdepositioninacerebellarcellmodelofjuvenileneuronalceroidlipofuscinosis", "role": "user" }, { "content": "[]", "role": "assistant" } ]

[ { "content": "Analyze the given text to identify specific entities. Focus on extracting relevant data.\n\nProvide your findings in JSON format. Each category should list the entities found.\n\nText:\n\nIsolation, characterisation and biological evaluation of a phenoxazine, a natural dyestuff isolated from leaves of Peristrophe bivalvis. Peristrophe bivalvis (L.) Merr. (Acanthaceae) is a wild growing and cultivated plant used for dyeing of foods by the ethnic minorities of Vietnam. The major component of the colour aqueous extract (CAE) of its leaves was identified as peristrophine by spectral analysis, especially the 2D NMR spectra (HSQC, HMBC and NOESY). Considering the widespread utilisation of the decoction of this plant for food dyeing, we evaluated the acute oral toxicity of the CAE. Based on the results in an acute toxicity study in mice, the LD50 value of the CAE was determined as 9100 ± 290 mg kg(-1) body weight. Additionally, in vitro cytotoxic assay showed an inhibition of peristrophine against Hepatocellular carcinoma (HepG2, IC503.90 µg mL(-1)). CAE and peristrophine (1) have also been tested for their ability to affect the cell number of the OCI acute myeloid leukaemia cell line. CAE and peristrophine significantly decreased the OCI cell number at different concentrations and times of treatment.", "role": "user" }, { "content": "{\"Chemical\": [\"phenoxazine\", \"peristrophine\"]}", "role": "assistant" } ]

[ { "content": "Given the full text of a scientific research paper, write an abstract section for the paper. Your response should contain only the abstract without any other text.\n\nArticle text:\nthe perfectly matched layer , or pml , is an absorbing boundary condition ( abc ) which was introduced in a paper by berenger @xcite .\nabcs are necessary when solving partial differential equations ( pdes ) using finite - difference time - domain ( fdtd ) methods or finite element methods ( fem ) over an open region .\nan efficient abc will save computer memory and processing time by truncating the domain and will minimize numerical reflections from the domain truncation .\nthe pml is reflectionless in theory , though some small reflection does occur in practice due to discretization .\nthe magnitude of this reflection is considerably smaller than that of other abcs , however ( for one comparison , see ref .\nit has been extensively used in the field of electromagnetics ( see refs .\n@xcite for example ) and has also found application in acoustical and geophysical work @xcite . to our knowledge , a pml has never been applied in numerical simulations of matter waves , such as bose - einstein condensates .\nimagine that we wish to simulate fluid flowing through a tube with a constriction and becoming supersonic , such as happens in a rocket engine or a laval nozzle , see fig\nsuch a system could be used as a laboratory analogue of a black hole @xcite , using a bose - einstein condensate for the fluid and laser light to provide the constriction .\nacoustic waves which have passed the constriction can not propagate back fast enough to return through it because of the fluid s supersonic flow .\nwe can say that a sonic horizon , which is analogous to the event horizon of a black hole and should share many of its properties , such as the production of hawking - like radiation , is formed at the narrowest point in the tube .\na supersonic nozzle is difficult to model computationally , because if we would impose the usual periodic boundary conditions we would need to slow down the flow to subsonic speed .\nthe process of turning a supersonic flow to a subsonic one is even more unstable than the converse @xcite and so periodic boundary conditions are unsuitable .\nthis is where the pml technique becomes useful .\nplacing a perfectly black layer at the supersonic end of the system allows us to model the condensate flow with much greater physical accuracy , by absorbing the supersonic matter waves and so simulating their propagation into free space .\nanother situation where the pml proves useful is in the simulation of the generation and propagation of waves with attractive nonlinear interaction , such as solitons .\nthe use of a pml layer at the edge of the computational domain can absorb the solitons , allowing us to ignore their fate and to focus on the area of interest .\nthe pml technique could be applied to the modelling of soliton propagation in a bec @xcite or in glass fibres @xcite , for example .\nthe concept of the pml for nonlinear and matter waves is similar to that for electromagnetic waves .\nthe essential idea is the use of transformations which map propagating solutions onto exponentially decaying evanescent waves in complex space .\nthus , waves travelling in the pml change from propagation in real space to propagation in imaginary space .\nthe idea of using complex space for waves originated with deschamps @xcite and the pml was first interpreted as a complex coordinate stretching by chew and weedon @xcite .\nhere we show how these ideas can be applied to nonlinear and matter waves .\nconsider first the standard linear schrdinger equation in one dimension , @xmath0 which can be written as @xmath1 where @xmath2 , the mass , has been split into two spatially dependent functions @xmath3 .\nsuppose that @xmath3 changes value from 1 at @xmath4 to i at @xmath5 .\nequation ( 2 ) has the general solution @xmath6 where the term inside the exponential is positive for waves moving to the left and negative for waves moving to the right .\nwe can choose @xmath3 to be , for example , @xmath7,\\ ] ] where the exponential is positive or negative depending on the direction of propagation of the waves in question .\n@xmath8 is the position where the pml starts and @xmath9 is a parameter which determines the sharpness of the transition between 1 and @xmath10 , which should be reasonably gradual , though our simulations indicate that the transition may be quite steep without any serious effects .\nthis implies that a matter wave may be stopped relatively rapidly .\nour introduction of @xmath3 is equivalent to making the transformation @xmath11 and writing @xmath12 essentially , we have transformed to a coordinate system that causes waves to exponentially decay as they approach @xmath13 .\nwe used a fdtd approach , discretizing via the crank - nicolson method @xcite .\nthis method has the advantage of being unconditionally stable due to its implicit nature and is second - order .\nthe system to be solved becomes @xmath17 \\\\\n! \\frac{|\\psi|^2}{2}\\left(\\psi(x , t+\\delta t ) + \\psi(x , t)\\right),\\\\\\end{aligned}\\ ] ] where @xmath18 . the tridiagonal system so produced is solved using the tridiagonal matrix algorithm or thomas algorithm @xcite .\nthe drawback to this discretization scheme is that it requires an additional level of detail , at half - steps in space .\nthis implies the need for a greater number of array elements and hence more computer operations and memory storage .\nmore complicated simulations , such as a condensate being forced through a nozzle by a piston , can take over 12 hours to complete on a pentium 4 3ghz pc .\nin a 1d computational domain 100 space units wide , travelling solitons are generated by a boundary condition on the right - hand side .\nthe virtual start point and velocity of the soliton can be specified by the user .\nas can be seen from the simulation data , the soliton travels until it reaches the pml boundary at @xmath19 where it gets stuck , begins to be absorbed and starts to spread out .\nthe peak value of @xmath20 quickly falls to less than @xmath21 of the initial value .\nthe simulation results show a condensate expanding without instabilities in a domain 100 space units in size , even with a relatively small pml ( 5 space units on the left- and right - hand sides ) . without the pml , monotonically\ngrowing instabilities occur in the expanding condensate and threaten the stability of the program . when we compared the expansion with the pml in place to expansion in a computational domain large enough that the expanding condensate does not touch its sides , no appreciable difference was evident , which indicates that the pml is functioning correctly .\nas our numerical simulations have shown , the perfectly matched layer can be used to good effect in nonlinear and matter wave simulations by truncating the domain , both for repulsive and attractive interactions .\nthe pml can be put to a wide variety of uses , for example in the modelling of sonic analogues of a black hole , expanding becs or soliton pulses propagating in free space and fibres .\none interesting feature is that the transition between real @xmath3 and imaginary @xmath3 may be relatively sharp in practice , which indicates that even supersonic condensates may be stopped quite abruptly . finally , the pml is of course capable of being extended to problems in more than one dimension . here\nthe variable @xmath22 in eqs .\n( 1 ) and ( 2 ) should be changed to refer to the normal direction of the boundary , while all other coordinates are unchanged .\nberenger , _ a perfectly matched layer for the absorption of electromagnetic waves , journal of computational physics _ * 114 * , 185 - 200 , 1994 w. v. andrew , c. a. balanis , p. a. tirkas , _ a comparison of the berenger perfectly matched layer and the lindman higher - order abcs for the fdtd method , ieee microwave and guided wave letters _\n, * 5(6 ) * : 192 - 194 , june 1995 r. mittra and . pekel , _ a new look at the perfectly matched layer ( pml ) concept for the reflectionless absorption of electromagnetic waves , ieee microwave and guided wave letters _ , * 5(3 ) * , 84 - 86 , march 1995 j. demoerloose , m. a. stuchly , _ behaviour of berenger abc for evanescent waves , ieee microwave and guided wave letters _ * 5(10 ) * : 344 - 346 , october 1995 z. wu and j. fang , _ numerical implementation and performance of perfectly matched layer boundary condition for waveguide structures , ieee transactions on microwave theory and techniques _ , *\n43(12 ) * , 2676 - 2683 , december 1995 j. c. veihl , r. mittra , _ an efficient implementation of berenger s perfectly matched layer ( pml ) for finite - difference time - domain mesh truncation , ieee microwave and guided wave letters _ * 6(2 ) * : 94 - 96 , february 1996 j. xu , j. g. ma , z. z. chen , _ numerical validations of a nonlinear pml scheme for absorption of nonlinear electromagnetic waves , ieee transactions on microwave theory and techniques _ * 46(11 ) * : 1752 - 1758 part 1 , november 1998 f. d. hastings , j. b. schneider , s. l. broschat , _ application of the perfectly matched layer ( pml ) absorbing boundary condition to elastic wave propagation , journal of the acoustical society of america _ , * 100(5 ) * : 3061 - 3069 , november 1996 q. h. liu , j. p. tao , _ the perfectly matched layer for acoustic waves in absorptive media , journal of the acoustical society of america _ , * 102(4 ) * : 2072 - 2082 , october 1997 y. q. zeng , q. h. liu , _ a staggered - grid finite - difference method with perfectly matched layers for poroelastic wave equations , journal of the acoustical society of america _ , * 109(6 ) * : 2571 - 2580 , june 2001 y. q. zeng , j. q. he , q. h. liu , _ the application of the perfectly matched layer in numerical modeling of wave propagation in poroelastic media , geophysics _\n, * 66 ( 4 ) * : 1258 - 1266 , july - august 2001 u. oguz , l. gurel , _ frequency responses of ground - penetrating radars operating over highly lossy grounds , ieee transactions ongeoscience and remote sensing _ , * 40(6 ) * : 1385 - 1394 , june 2002 w. g. unruh , _ sonic analogues of black holes and the effects of high frequencies of black hole evaporation , physical review d _ , * 51(6 ) * : 2827 - 2838 , march 1995 edited by m. novello , m. visser , g. e. volovik , _ artificial black holes _ , world scientific , 2002 u. leonhardt , t. kiss , and p. ohberg , _ theory of elementary excitations in unstable bose - einstein condensates and the instability of sonic horizons , phys .\na _ * 67 * , 033602 ( 2003 ) . k. e. strecker , g. b. partridge , a. g. truscott , r. g. hulet , _ formation and propagation of matter - wave soliton trains , nature _ * 417 * : 150 - 153 , may 9th 2002 g. p. agrawal , _ nonlinear fiber optics _ , academic press , san diego , 1995 g. a. deschamps , _\ngaussian beams as a bundle of complex rays , electronics letters _ * 7 * , 684 - 685 ( 1971 ) w. c. chew , w. weedon , _\na 3d perfectly matched medium from modified maxwell s equations wth stretched coordinates , microwave and optical technology letters _ * 7 * , 599 - 604 ( 1994 ) w. h. press , s. a. teukolsky , w. t. vetterling , b. p. flannery , _ numerical recipes in fortran 77 - the art of scientific computing , second edition _ , cambridge university press , 1992 l. h. thomas , _ elliptic problems in linear differential equations over a network , watson sci .\ncomp . lab . , columbia university , new york _", "role": "user" }, { "content": "we discuss how the perfectly matched layer ( pml ) can be adapted to numerical simulations of nonlinear and matter wave systems , such as bose - einstein condensates . \n we also present some examples which illustrate the benefits of using the pml in the simulation of nonlinear and matter waves . \n keywords : matter and nonlinear waves , absorbing boundary conditions .", "role": "assistant" } ]

[ { "content": "Craft a cohesive chapter for a literature review using the abstracts provided. Focus on the chapter's theme, weaving together insights and findings from the abstracts. Highlight key points and note any research gaps.\nLiterature Review Title: Learning Analytics for Learning Design: A Systematic Literature Review of Analytics-Driven Design to Enhance Learning \nChapter Title: C. Learning Design Taxonomy \n1. Abstract of Cited Paper (BIB001): There is an increased recognition that learning design drives both student learning experience and quality enhancements of teaching and learning. The Open University UK (OU) has been one of few institutions that have explicitly and systematically captured the designs for learning at a large scale. By applying advanced analytical techniques on large and fine-grained datasets, the OU has been unpacking the complexity of instructional practices, as well as providing conceptual and empirical evidence of how learning design influences student behaviour, satisfaction, and performance. This study discusses the implementation of learning design at the OU in the last ten years, and critically reviews empirical evidence from eight recent large-scale studies that have linked learning design with learning analytics. Four future research themes are identified to support future adoptions of learning design approaches. \n2. Abstract of Cited Paper (BIB002): The pedagogical modelling of everyday classroom practice is an interesting kind of evidence, both for educational research and teachers' own professional development. This paper explores the usage of wearable sensors and machine learning techniques to automatically extract orchestration graphs (teaching activities and their social plane over time), on a dataset of 12 classroom sessions enacted by two different teachers in different classroom settings. The dataset included mobile eye-tracking as well as audiovisual and accelerometry data from sensors worn by the teacher. We evaluated both time-independent and time-aware models, achieving median F1 scores of about 0.7-0.8 on leave-one-session-out k-fold cross-validation. Although these results show the feasibility of this approach, they also highlight the need for larger datasets, recorded in a wider variety of classroom settings, to provide automated tagging of classroom practice that can be used in everyday practice across multiple teachers.\n\nReview Chapter:", "role": "user" }, { "content": "The term learning design in this paper refers to the process of designing effective learning experiences with the use of technological innovations and resources. If effective, this process could be shared between educators and reused or adapted. Thus, there are several initiatives to create descriptive framework of instructional practices so that teaching approaches are shared among educators BIB002 . One of those initiatives is the Open University Learning Design Initiative, that categorize learning design in seven broad learning design activities BIB002 . Assimilative are learning activities in which students attend to information as required by their instructors; Finding and handling information includes learning activities which focus on skills development; Communicative activities encompass all communication between students, or students and instructors; Productive activities focus on active learning where students build artifacts; Experiential activities support students to apply their knowledge in real-world settings; Interactive/ adaptive activities include role-play, problem-based scenarios in simulated experiments; and finally assessment activities that include all forms of assessment. Having understanding of specific issues and phenomena during the implementation of learning design activities in technology-rich educational settings is of utmost importance BIB003 ; and in the same time very challenging to be addressed without the support of learning analytics. Moreover, there is no other classification of learning design concepts, that has been empirically used to compare, on a large scale, module designs across disciplines in university institutions BIB001 . Consequently, the authors want to explore what type of learning design activities have been used in the selected studies, and what learning analytics the researchers have applied to see how student's behavior relates to a specific learning activity. In particular, the focus is towards a well-designed learning design activities that provide foundation for effective scaffolding of student's learning behavior.", "role": "assistant" } ]