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Browsing publications of the research group genomeanalytics (GMAK) by Issue Date
Now showing items 1-20 of 130
Multiplex profiling of inflammation-related bioactive lipid mediators in Toxocara canis- and Toxocara cati-induced neurotoxocarosis.BACKGROUND: Somatic migration of Toxocara canis- and T. cati-larvae in humans may cause neurotoxocarosis (NT) when larvae accumulate and persist in the central nervous system (CNS). Host- or parasite-induced immunoregulatory processes contribute to the pathogenesis; however, detailed data on involvement of bioactive lipid mediators, e.g. oxylipins or eico-/docosanoids, which are involved in the complex molecular signalling network during infection and inflammation, are lacking. METHODOLOGY/PRINCIPAL FINDINGS: To elucidate if T. canis- and T. cati-induced NT affects the homeostasis of oxylipins during the course of infection, a comprehensive lipidomic profiling in brains (cerebra and cerebella) of experimentally infected C57BL/6J mice was conducted at six different time points post infection (pi) by liquid-chromatography coupled to electrospray tandem mass spectrometry (LC-ESI-MS/MS). Only minor changes were detected regarding pro-inflammatory prostaglandins (cyclooxygenase pathway). In contrast, a significant increase of metabolites resulting from lipoxygenase pathways was observed for both infection groups and brain regions, implicating a predominantly anti-inflammatory driven immune response. This observation was supported by a significantly increased 13-hydroxyoctadecadienoic acid (HODE)/9-HODE ratio during the subacute phase of infection, indicating an anti-inflammatory response to neuroinfection. Except for the specialised pro-resolving mediator (SPM) neuroprotectin D1 (NPD1), which was detected in mice infected with both pathogens during the subacute phase of infection, no other SPMs were detected. CONCLUSIONS/SIGNIFICANCE: The obtained results demonstrate the influence of Toxocara spp. on oxylipins as part of the immune response of the paratenic hosts. Furthermore, this study shows differences in the alteration of the oxylipin composition between T. canis- and T. cati-brain infection. Results contribute to a further understanding of the largely unknown pathogenesis and mechanisms of host-parasite interactions during NT.
Inactivation of Sox9 in fibroblasts reduces cardiac fibrosis and inflammationFibrotic scarring drives the progression of heart failure after myocardial infarction (MI). Therefore, the development of specific treatment regimens to counteract fibrosis is of high clinical relevance. The transcription factor SOX9 functions as an important regulator during embryogenesis, but recent data point towards an additional causal role in organ fibrosis. We show here that SOX9 is upregulated in the scar after MI in mice. Fibroblast specific deletion of Sox9 ameliorated MI-induced left ventricular dysfunction, dilatation and myocardial scarring in vivo. Unexpectedly, deletion of Sox9 also potently eliminated persisting leukocyte infiltration of the scar in the chronic phase after MI. RNA-sequencing from the infarct scar revealed that Sox9 deletion in fibroblasts resulted in strongly downregulated expression of genes related to extracellular matrix, proteolysis and inflammation. Importantly, Sox9 deletion in isolated cardiac fibroblasts in vitro similarly affected gene expression as in the cardiac scar and reduced fibroblast proliferation, migration and contraction capacity. Together, our data demonstrate that fibroblast SOX9 functions as a master regulator of cardiac fibrosis and inflammation and might constitute a novel therapeutic target during MI.
Neutrophils-related host factors associated with severe disease and fatality in patients with influenza infection.Severe influenza infection has no effective treatment available. One of the key barriers to developing host-directed therapy is a lack of reliable prognostic factors needed to guide such therapy. Here, we use a network analysis approach to identify host factors associated with severe influenza and fatal outcome. In influenza patients with moderate-to-severe diseases, we uncover a complex landscape of immunological pathways, with the main changes occurring in pathways related to circulating neutrophils. Patients with severe disease display excessive neutrophil extracellular traps formation, neutrophil-inflammation and delayed apoptosis, all of which have been associated with fatal outcome in animal models. Excessive neutrophil activation correlates with worsening oxygenation impairment and predicted fatal outcome (AUROC 0.817-0.898). These findings provide new evidence that neutrophil-dominated host response is associated with poor outcomes. Measuring neutrophil-related changes may improve risk stratification and patient selection, a critical first step in developing host-directed immune therapy.
Progressive Immunodeficiency with Gradual Depletion of B and CD4⁺ T Cells in Immunodeficiency, Centromeric Instability and Facial Anomalies Syndrome 2 (ICF2).Immunodeficiency, centromeric instability and facial anomalies syndrome 2 (ICF2) is a rare autosomal recessive primary immunodeficiency disorder. So far, 27 patients have been reported. Here, we present three siblings with ICF2 due to a homozygous ZBTB24 gene mutation (c.1222 T>G, p. (Cys408Gly)). Immune deficiency in these patients ranged from late-onset combined immunodeficiency (CID) with severe respiratory tract infections and recurrent shingles to asymptomatic selective antibody deficiency. Evident clinical heterogeneity manifested despite a common genetic background, suggesting the pathogenic relevance of epigenetic modification. Immunological follow-up reveals a previously unidentified gradual depletion of B and CD4+ T cells in all three presented patients with transition of a common variable immunodeficiency (CVID)-like disease to late-onset-CID in one of them. Considering all previously published cases with ICF2, we identify inadequate antibody responses to vaccines and reduction in CD27+ memory B cells as prevalent immunological traits. High mortality among ICF2 patients (20%) together with the progressive course of immunodeficiency suggest that hematopoietic stem cell transplantation (HSCT) should be considered as a treatment option in due time.
Therapeutic modulation of RNA-binding protein Rbm38 facilitates re-endothelialization after arterial injury.Aims Delayed re-endothelialization after balloon angioplasty in patients with coronary or peripheral artery disease impairs vascular healing and leads to neointimal proliferation. In the present study, we examined the effect of RNA-binding motif protein 38 (Rbm38) during re-endothelialization in a murine model of experimental vascular injury. Methods and results Left common carotid arteries of C57BL/6 mice were electrically denudated and endothelial regeneration was evaluated. Profiling of RNA-binding proteins revealed dysregulated expression of Rbm38 in the denudated and regenerated areas. We next tested the importance of Rbm38 in human umbilical vein endothelial cells (HUVECS) and analysed its effects on cellular proliferation, migration and apoptosis. Rbm38 silencing in vitro demonstrated important beneficial functional effects on migratory capacity and proliferation of endothelial cells. In vivo, local silencing of Rbm38 also improved re-endothelialization of denuded carotid arteries. Luciferase reporter assay identified miR-98 and let-7f to regulate Rbm38 and the positive proliferative properties of Rbm38 silencing in vitro and in vivo were mimicked by therapeutic overexpression of these miRNAs. Conclusion The present data identified Rbm38 as an important factor of the regulation of various endothelial cell functions. Local inhibition of Rbm38 as well as overexpression of the upstream regulators miR-98 and let-7f improved endothelial regeneration in vivo and thus may be a novel therapeutic entry point to avoid endothelial damage after balloon angioplasty.
Community richness of amphibian skin bacteria correlates with bioclimate at the global scale.Animal-associated microbiomes are integral to host health, yet key biotic and abiotic factors that shape host-associated microbial communities at the global scale remain poorly understood. We investigated global patterns in amphibian skin bacterial communities, incorporating samples from 2,349 individuals representing 205 amphibian species across a broad biogeographic range. We analysed how biotic and abiotic factors correlate with skin microbial communities using multiple statistical approaches. Global amphibian skin bacterial richness was consistently correlated with temperature-associated factors. We found more diverse skin microbiomes in environments with colder winters and less stable thermal conditions compared with environments with warm winters and less annual temperature variation. We used bioinformatically predicted bacterial growth rates, dormancy genes and antibiotic synthesis genes, as well as inferred bacterial thermal growth optima to propose mechanistic hypotheses that may explain the observed patterns. We conclude that temporal and spatial characteristics of the host's macro-environment mediate microbial diversity.
Integrated Transcriptional Regulatory Network of Quorum Sensing, Replication Control, and SOS Response in .Quorum sensing (QS) coordinates population wide gene expression of bacterial species. Highly adaptive traits like gene transfer agents (GTA), morphological heterogeneity, type 4 secretion systems (T4SS), and flagella are QS controlled in Dinoroseobacter shibae, a Roseobacter model organism. Its QS regulatory network is integrated with the CtrA phosphorelay that controls cell division in alphaproteobacteria. To elucidate the network topology, we analyzed the transcriptional response of the QS-negative D. shibae strain ΔluxI1 toward externally added autoinducer (AI) over a time period of 3 h. The signaling cascade is initiated by the CtrA phosphorelay, followed by the QS genes and other target genes, including the second messenger c-di-GMP, competence, flagella and pili. Identification of transcription factor binding sites in promoters of QS induced genes revealed the integration of QS, CtrA phosphorelay and the SOS stress response mediated by LexA. The concentration of regulatory genes located close to the origin or terminus of replication suggests that gene regulation and replication are tightly coupled. Indeed, addition of AI first stimulates and then represses replication. The restart of replication comes along with increased c-di-GMP levels. We propose a model in which QS induces replication followed by differentiation into GTA producing and non-producing cells. CtrA-activity is controlled by the c-di-GMP level, allowing some of the daughter cells to replicate again. The size of the GTA producing subpopulation is tightly controlled by QS via the AI Synthase LuxI2. Finally, induction of the SOS response allows for integration of GTA DNA into the host chromosome.
Interferon-beta expression and type I interferon receptor signaling of hepatocytes prevent hepatic necrosis and virus dissemination in Coxsackievirus B3-infected mice.During Coxsackievirus B3 (CVB3) infection hepatitis is a potentially life threatening complication, particularly in newborns. Studies with type I interferon (IFN-I) receptor (IFNAR)-deficient mice revealed a key role of the IFN-I axis in the protection against CVB3 infection, whereas the source of IFN-I and cell types that have to be IFNAR triggered in order to promote survival are still unknown. We found that CVB3 infected IFN-β reporter mice showed effective reporter induction, especially in hepatocytes and only to a minor extent in liver-resident macrophages. Accordingly, upon in vitro CVB3 infection of primary hepatocytes from murine or human origin abundant IFN-β responses were induced. To identify sites of IFNAR-triggering we performed experiments with Mx reporter mice, which upon CVB3 infection showed massive luciferase induction in the liver. Immunohistological studies revealed that during CVB3 infection MX1 expression of hepatocytes was induced primarily by IFNAR-, and not by IFN-III receptor (IFNLR)-triggering. CVB3 infection studies with primary human hepatocytes, in which either the IFN-I or the IFN-III axis was inhibited, also indicated that primarily IFNAR-, and to a lesser extent IFNLR-triggering was needed for ISG induction. Interestingly, CVB3 infected mice with a hepatocyte-specific IFNAR ablation showed severe liver cell necrosis and ubiquitous viral dissemination that resulted in lethal disease, as similarly detected in classical IFNAR-/- mice. In conclusion, we found that during CVB3 infection hepatocytes are major IFN-I producers and that the liver is also the organ that shows strong IFNAR-triggering. Importantly, hepatocytes need to be IFNAR-triggered in order to prevent virus dissemination and to assure survival. These data are compatible with the hypothesis that during CVB3 infection hepatocytes serve as important IFN-I producers and sensors not only in the murine, but also in the human system.
Metatranscriptome Analysis of the Vaginal Microbiota Reveals Potential Mechanisms for Protection against Metronidazole in Bacterial Vaginosis.Bacterial vaginosis (BV) is a prevalent multifactorial disease of women in their reproductive years characterized by a shift from the
Exome sequencing and case-control analyses identify RCC1 as a candidate breast cancer susceptibility gene.Breast cancer is a genetic disease but the known genes explain a minority of cases. To elucidate the molecular basis of breast cancer in the Tunisian population, we performed exome sequencing on six BRCA1/BRCA2 mutation-negative patients with familial breast cancer and identified a novel frameshift mutation in RCC1, encoding the Regulator of Chromosome Condensation 1. Subsequent genotyping detected the 19-bp deletion in additional 5 out of 153 (3%) breast cancer patients but in none of 400 female controls (p = 0.0015). The deletion was enriched in patients with a positive family history (5%, p = 0.0009) and co-segregated with breast cancer in the initial pedigree. The mutant allele was lost in 4/6 breast tumors from mutation carriers which may be consistent with the hypothesis that RCC1 dysfunction provides a selective disadvantage at the stage of tumor progression. In summary, we propose RCC1 as a likely breast cancer susceptibility gene in the Tunisian population.
Birth, evolution, and transmission of satellite-free mammalian centromeric domains.Mammalian centromeres are associated with highly repetitive DNA (satellite DNA), which has so far hindered molecular analysis of this chromatin domain. Centromeres are epigenetically specified, and binding of the CENPA protein is their main determinant. In previous work, we described the first example of a natural satellite-free centromere on
AgNPs Change Microbial Community Structures of Wastewater.Due to their strong antimicrobial activity, silver nanoparticles (AgNPs) are massively produced, applied, consumed and, as a negative consequence, released into wastewater treatment plants. Most AgNPs are assumed to be bound by sludge, and thus bear potential risk for microbial performance and stability. In this lab-scale study, flow cytometry as a high-throughput method and 16S rRNA gene amplicon Illumina MiSeq sequencing were used to track microbial community structure changes when being exposed to AgNPs. Both methods allowed deeper investigation of the toxic impact of chemicals on microbial communities than classical EC50 determination. In addition, ecological metrics were used to quantify microbial community variations depending on AgNP types (10 and 30 nm) and concentrations. Only low changes in α- and intra-community β-diversity values were found both in successive negative and positive control batches and batches that were run with AgNPs below the EC50 value. Instead, AgNPs at EC50 concentrations caused upcoming of certain and disappearance of formerly dominant subcommunities. Flavobacteriia were among those that almost disappeared, while phylotypes affiliated with Gammaproteobacteria (3.6-fold) and Bacilli (8.4-fold) increased in cell abundance in comparison to the negative control. Thus, silver amounts at the EC50 value affected community structure suggesting a potential negative impact on functions in wastewater treatment systems.
Distribution and Evolution of Peroxisomes in Alveolates (Apicomplexa, Dinoflagellates, Ciliates).The peroxisome was the last organelle to be discovered and five decades later it is still the Cinderella of eukaryotic compartments. Peroxisomes have a crucial role in the detoxification of reactive oxygen species, the beta-oxidation of fatty acids, and the biosynthesis of etherphospholipids, and they are assumed to be present in virtually all aerobic eukaryotes. Apicomplexan parasites including the malaria and toxoplasmosis agents were described as the first group of mitochondriate protists devoid of peroxisomes. This study was initiated to reassess the distribution and evolution of peroxisomes in the superensemble Alveolata (apicomplexans, dinoflagellates, ciliates). We established transcriptome data from two chromerid algae (Chromera velia, Vitrella brassicaformis), and two dinoflagellates (Prorocentrum minimum, Perkinsus olseni) and identified the complete set of essential peroxins in all four reference species. Our comparative genome analysis provides unequivocal evidence for the presence of peroxisomes in Toxoplasma gondii and related genera. Our working hypothesis of a common peroxisomal origin of all alveolates is supported by phylogenetic analyses of essential markers such as the import receptor Pex5. Vitrella harbors the most comprehensive set of peroxisomal proteins including the catalase and the glyoxylate cycle and it is thus a promising model organism to investigate the functional role of this organelle in Apicomplexa.
Packaging of Dinoroseobacter shibae DNA into Gene Transfer Agent Particles Is Not Random.Gene transfer agents (GTAs) are phage-like particles which contain a fragment of genomic DNA of the bacterial or archaeal producer and deliver this to a recipient cell. GTA gene clusters are present in the genomes of almost all marine Rhodobacteraceae (Roseobacters) and might be important contributors to horizontal gene transfer in the world's oceans. For all organisms studied so far, no obvious evidence of sequence specificity or other nonrandom process responsible for packaging genomic DNA into GTAs has been found. Here, we show that knock-out of an autoinducer synthase gene of Dinoroseobacter shibae resulted in overproduction and release of functional GTA particles (DsGTA). Next-generation sequencing of the 4.2-kb DNA fragments isolated from DsGTAs revealed that packaging was not random. DNA from low-GC conjugative plasmids but not from high-GC chromids was excluded from packaging. Seven chromosomal regions were strongly overrepresented in DNA isolated from DsGTA. These packaging peaks lacked identifiable conserved sequence motifs that might represent recognition sites for the GTA terminase complex. Low-GC regions of the chromosome, including the origin and terminus of replication, were underrepresented in DNA isolated from DsGTAs. DNA methylation reduced packaging frequency while the level of gene expression had no influence. Chromosomal regions found to be over- and underrepresented in DsGTA-DNA were regularly spaced. We propose that a "headful" type of packaging is initiated at the sites of coverage peaks and, after linearization of the chromosomal DNA, proceeds in both directions from the initiation site. GC-content, DNA-modifications, and chromatin structure might influence at which sides GTA packaging can be initiated.
Decreased production of class-switched antibodies in neonatal B cells is associated with increased expression of miR-181b.The increased susceptibility to infections of neonates is caused by an immaturity of the immune system as a result of both qualitative and quantitative differences between neonatal and adult immune cells. With respect to B cells, neonatal antibody responses are known to be decreased. Accountable for this is an altered composition of the neonatal B cell compartment towards more immature B cells. However, it remains unclear whether the functionality of individual neonatal B cell subsets is altered as well. In the current study we therefore compared phenotypical and functional characteristics of corresponding neonatal and adult B cell subpopulations. No phenotypic differences could be identified with the exception of higher IgM expression in neonatal B cells. Functional analysis revealed differences in proliferation, survival, and B cell receptor signaling. Most importantly, neonatal B cells showed severely impaired class-switch recombination (CSR) to IgG and IgA. This was associated with increased expression of miR-181b in neonatal B cells. Deficiency of miR-181b resulted in increased CSR. With this, our results highlight intrinsic differences that contribute to weaker B cell antibody responses in newborns.
Global micro RNA expression profiling in the liver biopsies of Hepatitis B Virus infected patients suggests specific miRNA signatures for viral persistence and hepatocellular injury.Hepatitis B virus (HBV) can manipulate the miRNA regulatory networks in infected cells to create a permissive environment for viral replication, cellular injury, disease onset and its progression. The aim of the present study was to understand the miRNA networks and their target genes in the liver of hepatitis B patients involved in HBV replication, liver injury and liver fibrosis. We investigated differentially expressed miRNAs by microarray in the liver biopsy samples from different stages of HBV infection and liver disease [immune tolerant (IT; n= 8); acute viral hepatitis (AVH; n=8); no fibrosis (n=16); early (F1+F2) (n=19) or late fibrosis (F3+F4) (n=14) and healthy controls (n=7)]. The miRNA expression levels were analyzed by the unsupervised principal component analysis (PCA) and hierarchical clustering. Analysis of miRNA-mRNA regulatory networks identified 17 miRNAs and 18 target gene interactions with four distinct nodes each representing a stage-specific gene regulation during disease progression. The IT group showed elevated miR-199a-5p, miR-221-3p and Let-7a-3p levels which could target genes involved in innate immune response and viral replication. In AVH group, miR-125b-5p and miR-3613-3p were up whereas miR-940 was down which might affect cell proliferation via STAT3 pathway. In early fibrosis, miR-34b-3p, miR-1224-3p and miR-1227-3p were up while miR-499a-5p was down which together, possibly mediate chronic inflammation. In advanced fibrosis, miR-1, miR-10b-5p, miR-96-5p, miR-133b and miR-671-5p were up while miR-20b-5p and miR-455-3p were down, possibly allowing chronic disease progression. Interestingly, only 8 of 17 liver-specific miRNAs exhibited a similar expression pattern in patient sera.
The Biofilm Inhibitor Carolacton Enters Gram-Negative Cells: Studies Using a TolC-Deficient Strain of Escherichia coli.The myxobacterial secondary metabolite carolacton inhibits growth of Streptococcus pneumoniae and kills biofilm cells of the caries- and endocarditis-associated pathogen Streptococcus mutans at nanomolar concentrations. Here, we studied the response to carolacton of an Escherichia coli strain that lacked the outer membrane protein TolC. Whole-genome sequencing of the laboratory E. coli strain TolC revealed the integration of an insertion element, IS5, at the tolC locus and a close phylogenetic relationship to the ancient E. coli K-12. We demonstrated via transcriptome sequencing (RNA-seq) and determination of MIC values that carolacton penetrates the phospholipid bilayer of the Gram-negative cell envelope and inhibits growth of E. coli TolC at similar concentrations as for streptococci. This inhibition is completely lost for a C-9 (R) epimer of carolacton, a derivative with an inverted stereocenter at carbon atom 9 [(S) → (R)] as the sole difference from the native molecule, which is also inactive in S. pneumoniae and S. mutans, suggesting a specific interaction of native carolacton with a conserved cellular target present in bacterial phyla as distantly related as Firmicutes and Proteobacteria. The efflux pump inhibitor (EPI) phenylalanine arginine β-naphthylamide (PAβN), which specifically inhibits AcrAB-TolC, renders E. coli susceptible to carolacton. Our data indicate that carolacton has potential for use in antimicrobial chemotherapy against Gram-negative bacteria, as a single drug or in combination with EPIs. Strain E. coli TolC has been deposited at the DSMZ; together with the associated RNA-seq data and MIC values, it can be used as a reference during future screenings for novel bioactive compounds. IMPORTANCE The emergence of pathogens resistant against most or all of the antibiotics currently used in human therapy is a global threat, and therefore the search for antimicrobials with novel targets and modes of action is of utmost importance. The myxobacterial secondary metabolite carolacton had previously been shown to inhibit biofilm formation and growth of streptococci. Here, we investigated if carolacton could act against Gram-negative bacteria, which are difficult targets because of their double-layered cytoplasmic envelope. We found that the model organism Escherichia coli is susceptible to carolacton, similar to the Gram-positive Streptococcus pneumoniae, if its multidrug efflux system AcrAB-TolC is either inactivated genetically, by disruption of the tolC gene, or physiologically by coadministering an efflux pump inhibitor. A carolacton epimer that has a different steric configuration at carbon atom 9 is completely inactive, suggesting that carolacton may interact with the same molecular target in both Gram-positive and Gram-negative bacteria.
Draft Genome Sequence of Zoonotic Streptococcus canis Isolate G361.Here, we report the draft genome sequence of an SCM-positive Streptococcus canis strain, G361, isolated from a vaginal swab of a 40-year-old woman. The draft genome comprises 2,045,931 bp in 62 contigs.
Phylotranscriptomic consolidation of the jawed vertebrate timetree.Phylogenomics is extremely powerful but introduces new challenges as no agreement exists on "standards" for data selection, curation and tree inference. We use jawed vertebrates (Gnathostomata) as model to address these issues. Despite considerable efforts in resolving their evolutionary history and macroevolution, few studies have included a full phylogenetic diversity of gnathostomes and some relationships remain controversial. We tested a novel bioinformatic pipeline to assemble large and accurate phylogenomic datasets from RNA sequencing and find this phylotranscriptomic approach successful and highly cost-effective. Increased sequencing effort up to ca. 10Gbp allows recovering more genes, but shallower sequencing (1.5Gbp) is sufficient to obtain thousands of full-length orthologous transcripts. We reconstruct a robust and strongly supported timetree of jawed vertebrates using 7,189 nuclear genes from 100 taxa, including 23 new transcriptomes from previously unsampled key species. Gene jackknifing of genomic data corroborates the robustness of our tree and allows calculating genome-wide divergence times by overcoming gene sampling bias. Mitochondrial genomes prove insufficient to resolve the deepest relationships because of limited signal and among-lineage rate heterogeneity. Our analyses emphasize the importance of large curated nuclear datasets to increase the accuracy of phylogenomics and provide a reference framework for the evolutionary history of jawed vertebrates.
Complete Genome Sequence of JII-1961, a Bovine Mycobacterium avium subsp. paratuberculosis Field Isolate from Germany.Mycobacterium avium subsp. paratuberculosis causes Johne's disease in ruminants and was also detected in nonruminant species, including human beings, and in milk products. We announce here the 4.829-Mb complete genome sequence of the cattle-type strain JII-1961 from Germany, which is very similar to cattle-type strains recovered from different continents.


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The campus has a well stocked, multi-layered library with a modern collection of knowledge resources and innovative information services to fulfill the needs of the students, faculty members and the surrounding community in their intellectual pursuits. A need based collection of knowledge resources is aligned to the vision and mission of the School. It includes resources like books predominantly related to management and allied subjects, social issues, autobiographies, encyclopedias, journals, educational videos etc.
Library has a well-maintained Digital Library with on-line connectivity of twenty terminals. It is very useful for information seekers. The digital library has needful collection of CD-ROM, e-Journals, on-line Journals. The digital library also has twenty computers in digital sections of various departments and all are connected through LAN systems.
The College has separate hotels for girls and boys with round the clock security arrangements, each hostels has separate dining rooms, recreation rooms and study rooms.
The College has its own fleet of over --- buses that ply on several routes across NCR and its neighboring areas, serving both students and staff. Bus facilities are also available to hostellers for visits to the city. Students are charged on the basis of actual.
The Seminar Hall is the ideal venue for seminars and medical professional members to talk and deliver lectures to the students of our college to provide them a better and closer insight into the working of their different fields.
The Institute provides facility for banking at campus. The BOB has provided ATM facility at Campus for the convenience of the students, staff as well as the general public.

subset: commoncrawl


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Double Fine Productions
Finding Time for Games and "Sweet Revenge:" An Interview with Double Fine's Tim Schafer
We talk to industry veteran Tim Schafer about developing games with Microsoft, his favorite games, and the inspirational powers behind cult RPG Skies of Arcadia.
Samurai Gunn 2 is Looking For Its Street Fighter 2 Moment
The local competitive darling is ready for its big break.
Charming Adventure Game Knights and Bikes Finally Gets a Release Date
This Goonies-esque adventure will be here pretty soon.
Psychonauts 2 Reminds Us Why Double Fine is the Boss of Comedy Games
The Xbox and PS2 cult classic's spirit is alive and well in the modern generation.
THQ Nordic Turns to the Darksiders
THIS WEEK IN BUSINESS | De Blob publisher DeBases itself hanging out with DeBigots to promote its games.
Half-Life 2, Portal Writer Erik Wolpaw Returns to Valve [Update: On a Contractual Basis]
Update: Wolpaw is not full-time at Valve.
Knights and Bikes, the Kickstarter Success Story with Double Fine's Backing
The developers behind Knights and Bikes have some words of wisdom from going through Kickstarter.
Psychonauts 2 Will Miss Its 2018 Release
Double Fine announced that the game has slipped its planned 2018 release.
Double Fine's Amnesia Fortnight 2017 Jams On Over at Humble Bundle
Folks can head over to Humble Bundle to vote on the latest small project from the minds at Double Fine.
Costume Quest Animated Series Coming From Amazon
Double Fine's RPG is turning into a cartoon from Federator Studios.
Psychonauts 2 Will Be Published By Starbreeze in 2018
Double Fine's adventure sequel is coming from a new publisher.
Double Fine is Publishing a Console Release of the Rhythm Game 140
Look for the funky minimalistic rhythm / platforming hybrid this summer.
Day of the Tentacle Remastered PC Review: Time After Time
Double Fine finally dusts off one of history's greatest adventure games of all time for a special edition that's not to be missed.
Behind the Art of Day of the Tentacle
COVER STORY: LucasArts alumni Peter Chan and Larry Ahern chat about the challenges of making a "cartoon adventure" under the constraints of early '90s technology.
Day of the Devs Returns to San Francisco on November 7th
...And even if you aren't a Bay Area resident, you can still check out this showcase of upcoming indie games via Twitch.
Axe of the Blood God Episode 14: The First 70 Hours of Xenoblade Chronicles X
Plus: Double Fine's Brad Muir drops by to talk about Massive Chalice.
Broken Age Act Two PC Review: Childhood Lost
Act Two of the Double Fine Adventure doesn't quite live up to the first.
Grim Fandango Remastered PS4 Review: A Bone to Pick
Tim Schafer's 1998 tribute to film noir spins a gripping tale, but its unfriendly puzzles will have many calling it quits before the final curtain.
Massive Chalice: Queen Adamanita's Eugenics Diary
We uncover the darker side of Double Fine's tactical RPG.
Game Dev Recipes: Massive Chalice
How Double Fine's upcoming tactical RPG draws inspiration from XCOM, Final Fantasy Tactics, and oddly enough, Mega Man.
Hack 'n' Slash Toys with the Zelda Formula, but Restores one Element Nintendo's Series Left Behind
Double Fine's inventive take on old-school adventuring lets players manipulate the world around them through the power of code.
PAX Prime 2014: 10 Bone-Chilling Facts About Grim Fandango Remastered
Tim Schafer's panel on his 1998 classic's re-release leaked plenty of tantalizing details about the game's past and present development.
PAX Prime 2014: Massive Chalice and Strategy Gaming's Next Act
Double Fine's generational strategy game takes the best elements of XCOM and Fire Emblem and blends them into something new.
PAX Prime 2014: Costume Quest 2 Aims to Fix the First Game's Greatest Flaw
The sequel to one of 2010's nicest surprises offers a snappier take on the original's slow-paced battle mechanics.
Popular Games


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About this Event
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We will take the opportunity at this event to recognise Executive Partners who have served the Program for five years or more with Long Service Mentor Awards. The recipient of the Peter McInnes Memorial Travel Grant, Julie Cao, will share her William and Mary Exchange experience and how the EPP has accelerated her personal and professional growth.
Please join us to celebrate your contribution and impact in the 2019 Executive Partners Program with your fellow EPs and mentees.


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Scale snorkel made of rubber which allows it to stay upright but also able to bend if your truck is rolled over to prevent it from breaking. Can be trimmed/cut to fit other trucks.
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text: Holland & Barrett Brown Linseed 500g €3.39 Wait, don't go! Free Standard Delivery when you spend €20 Zoom Click image to zoom Close Click and hold image for a closer look Select Size: 500 g  125 g  12 rewards for life points SKU: 080666 €3.39 €0.68/100 g In Stock 500 g €0.68/100 g 080666 €3.39 12 rewards for life points In Stock 4 rewards for life points SKU: 017727 €1.49 €1.19/100 g In Stock 125 g €1.19/100 g 017727 €1.49 4 rewards for life points In Stock Quantity: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 Add to favourites Standard Delivery STANDARD DELIVERY €2.99 or Free on orders over €20 Order before 9pm to get your delivery within 4 working days between 8am - 9am €2.99 or FREE on spending €20. Delivery within 4 working days Express Delivery EXPRESS DELIVERY €3.99 or Free when you spend €60 Order before 6pm for express delivery, 7 days a week. Orders placed after 9pm will be delivered on the following day Free Express Delivery when you spend €60 - Order before 8pm Express Click & Collect Express CLICK & COLLECT Free on all orders Order online by 9pm today and we'll deliver to your chosen Holland & Barrett store in 1 working days FREE on all orders Delivery within 1 working day Description Source of Protein High in dietary fibre Great for adding texture to your soups, salads and stir-fry's Holland & Barrett Brown Linseed are rich in vitamin B6 and magnesium as well as being a great source of protein. Sprinkle on your oats in the morning for a healthy kick start to your day! Did you know that these little fellas are rich in calcium and iron and are sometimes known as 'flaxseed'? show more show less Nutritional Information: Nutritional Information: Typical Analysis per 100g: Energy 2234KJ / 534Kcal Fat 42g Of Which Saturates 3.7g Carbohydrates 1.6g Of which sugars 1.6g Fibre 27g Protein 18g Salt 0.08g Thiamin 1.6mg (145% RI) Vitamin B6 0.5mg (35% RI) Magnesium 392mg (104%) Phosphorous 842mg (92% RI) RI = Reference Intake Reference Intake of an average adult (8400KJ/2000Kcal). show more show less Additional Info Directions: Take one tablespoon (approx 12g) two or three times a day immediately followed by two glasses of water, fruit juice or milk. After a few weeks liquid may be reduced depending on your own experience. Ingredients: Linseed. May contain Nuts, Peanuts, Sesame Seeds. Remember: Although we make every effort to ensure our product information is up to date on our website, please always read labels, warnings, and directions provided with the product before using or consuming the product. show more show less Free from Free from Vegan bvseo_sdk, java_sdk, bvseo-4.0.0 CLOUD, getContent, 0ms REVIEWS, PRODUCT bvseo-msg: EXECUTION_TIMEOUT is set to 0 ms; JavaScript-only Display.


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Products 1 - 40 of 62 - Continental Travel Contact Tire (x42). $ $ Pick Size Continental Contact Travel Tire (Folding Bead) (Black). $
Cross-Hybrid Defined Color: Black Tire Type: Clincher Tire Diameter: Steel PSI: Powered by TurnTo.
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Home Menu Search. For the purpose of terminology consistency, I may be referring to the tires found on the Schwalbe tire website, one of several tires brands Continental travel contact 700 have used for touring. I have no affiliation with Schwalbe as I have also used tires for touring from Vittoria, Continental, Panaracer and Specialized.
As a general statement, durability can simply be defined as any tire that completes the intended bike tour. As a technical definition, durability refers not only continental travel contact 700 the number of miles the tread will last, but also to how well the sidewalls hold up to cracking and resisting cuts.
Some tires will have an additional continentxl resistance layer incorporated into the tire. Keep in mind that changing schwinn handle grips tire due to wear can be a planned part of your bike travels in order to ride on a lighter tire.
You will find that the more durable the 700 35 the heavier it will be. In my experience, probably all cyclists traveling around the world that have stayed at my house use tires in the gram range.
I have also had a cyclist traveling across the U. Flats are always an annoying part of any tour.
I think a flat-protection layer is a nice feature on a tire designed for bike travel. There are several in-house brands 26 hybrid tires manufacturers and several types of flat proofing incorporated in a tire continental travel contact 700 by a tire manufacturer such as Schwalbe.
I do not have enough experience or engineering knowledge trxvel rate the different types. Nearly all of my flats occur for a couple of reasons.
I run my tires too long so I get flats due to excess wear. The second reason is simply bad luck.
Another source of flats is on roads frequented by heavy trucks. The flats come from staple-like pieces of metal thrown from truck tires due to wear.
Julie and I have traveel a combined miles with one flat on some of our tours. On our mile Canadian Rockies tour neither one of us had a flat. Stability is a subjective term.
The Schwalbe website uses the term grip. I contaxt stability as a general term for how well does the tire handle continental travel contact 700 wet weather, on loose casual rider sitting on a paved road or as the material of a dirt roadrolling over small potholes or obstacles on a road and cornering, down a mountain pass.
News:golddragon.info: Continental Travel Contact Urban Bicycle Tire (26x): Bike Tires: Sports & Outdoors. Continental Tour Ride x 28c Bike Tire. out of 5 . If you're going to ride on both dirt and pavement, they are an excellent choice.
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Green Tea by Elizabeth Arden Gift Set Women's Perfume - 3pc
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Tag Archives: violence
One of the more blatant contradictions of today's media (and that's saying a lot) is the attitudes towards sex and violence. On the one hand, violence is borderline glorified with movies, TV shows, video games, and even the news making … Continue reading
Posted in Current Events/Political Issues, TV/Movies Tagged contradiction, death, media, movies, news, porn, sex, TV, violence, war, weapons Leave a comment
Grand Theft Auto V and Violent Video Games
With the release of Grand Theft Auto V this week, the age-old question of violent video games and their impact on society has once again been raised. As video games get more and more realistic, the concern of their impact … Continue reading
Posted in Video Games Tagged Grand Theft Auto V, mature, mentally unstable, oculus rift, violence, violent video games, virtual reality 2 Comments
Would We Be Better off Without Emotions?
Emotion is such a complex concept. Emotions have the power to do some of the greatest good but also some of the worst evil. Positive emotions make us feel good and give our body feelings of pleasure. Negative emotions lead … Continue reading
Posted in Deep Thoughts Tagged anger, corruption, emotions, evil, happiness, hatred, joy, logic, love, negative emotions, pain, positive emotions, society, violence, war 14 Comments


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New Music Friday Alert For February 23rd!
Every Friday is about New Music! This week, we have brand new music from 5 Seconds Of Summer, Post Malone, Logic, David Guetta, Janelle Monae, and more!
Want You Back - 5 Seconds Of Summer
The boys of the Australian boyband, 5 Seconds Of Summer - Luke Hemmings, Calum Hood, Michael Clifford, and Ashton Irwin - are back with brand new music after a bit of a hiatus with Want You Back! The guys posted on Instagram that they will be dropping the new music and originally teased the track would be dropping February 19th but it changed to February 23rd later that day so just had to cling to the edge of our seats for an extra few days but it is finally here! #5SOS3ISCOMING has been their official hashtag too, getting 5SOS fans anxious for an entire new album! And they are also going back on tour!
"No matter where I go, I'm always gonna want you back // No matter how long you're gone, I'm always gonna want you back."
5SOS became popular in the states in 2014 with their hit tracks, She Looks So Perfect, Amnesia, and more off their 5 Seconds Of Summer album.
Psycho - Post Malone featuring Ty Dolla $ign
This track, Psycho, from Post Malone featuring Ty Dolla $ign has people super anxious and excited for all the right reasons. Post Malone received a huge following after his track Congratulations that hit mainstream and has had other hits since including Rockstar with 21 Savage.
44 More - Logic
Logic is dropping has dropped new music called 44 More! Yes, the title includes numbers like his other mainstream and popular track, 1-800-273-8255 with Alessia Cara and Khalid, that really triggered a conversation in our society about suicide as well as suicide prevention.
Like I Do - David Guetta, Martin Garrix, & Brooks
Guetta, Garrix & Brooks teamed up for their new track Like I Do that dropped Thursday morning! The two famous DJs - Guetta and Garrix teamed up to produce this track for Brooks and it just go so well together. It it basically next level EDM - it what you get when you put two EDM masterminds together on one track. FIRE!
Next To Me - Imagine Dragons
Imagine Dragons dropped brand new music Wednesday called Next To Me and dropped news that they will be going on another tour, Evolve Tour, this summer. Grace Vanderwaal, the 14-year-old winner of America's Got Talent, will be opening up for most of their shows. Tickets go on sale to the public February 27th on Ticketmaster.
Aurora Album - Bea Miller
Bea Miller just dropped an entire album called Aurora including Bored, Song Like You, Motherlove, and more! A lot of us have been waiting a while for her album but it is finally here! It is Miller's second album and includes 5 previous EPs! This album shows just a sample of what Miller is capable of and we cannot wait for more!
Django Jane - Janelle Monae
Monae just dropped Django Jane Thursday afternoon and it is unreal! It is literally if Kendrick Lamar and Alicia Keys had a kid, it would be Janelle Monae. She is spitting tracks with the pure elegant rhythm. Monae also dropped another track that she wrote with Justin Tranter and Julia Michaels that has a bit of a popish flair to it called Make Me Feel! It has the potential to be this huge iconic anthem like something Whitney Houston or Madonna would have had in their rolodex of music.


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Well, folks, this life changing move of mine just got real. I got into the apartment building that I so badly wanted.
When I lost my sister, I went through such a dark time. I didn't know what I needed to get out of that misery, but I tried looking. Turns out it wasn't a person or a situation. It was a place. This place that I am in.
I never had a doubt that God was going to bless me with what I needed but, this time, what I needed just happened to also be what I wanted. That doesn't happen very often.
This is just a post to give thanks to God and to the people he put in my life. Peoplake who prayed for me when I was so depressed the past couple of years. People who gave to me when they didn't have to. People who just let me drench their shoulders with my tears when I needed.
I'm thankful to my family who supported me and helped me along the way. I am truly blessed - not just in good times but also in times of sadness.
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UPDATE: I sent a question to Greek Bliss about their foot balm and body butter. I heard back and they were nice enough to send me a code to...
This is a copy of the post from my other blog (Banned by Amazon). Until that blog starts getting more traffic, I will be mirroring the post...
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Krenzen Auto Mall
19 Lifetime Reviews2500 Mall Drive, Duluth, Minnesota 55811 Directions Directions
Is this your dealership?
...and take advantage of all we have to offer with our Certified Dealership Program.
19 Reviews of Krenzen Auto Mall
"Worst Customer Service I have ever received"- disappointed
Had to have my brand new Nissan Murano towed to Duluth because Krenzen said do not drive it, and at 1200 miles they refused to honor the warranty. They said I hit something (although I did not) because a small plastic part under my car was scratched. I ask if it was possible that I did not hit something and it was a defective part. They said yes it's possible but we can not turn this in to Nissan for the warranty. They charged me 370.00 dollars for the small part. My car was filthy when I picked it up and smelled like smoke. Never treated so poorly by a service department. Later they told me I'm not a customer because I did not buy my car there. They are correct, I WILL NEVER be a customer there again.Read More
"Taken advantage of by typical Car salesmen"- SadRoguegirl
I was shopping for a used Nissan Rogue. I wanted to shop out of town but my husband did not want to travel so we ended up at Krenzen. The shopping experience was fine; we test drove quite a few vehicles. It came down to two and we made a decision. We did not get a single cent off the price and we paid extra for the "environmental" package. With this I was told that the car would be fully detailed since they have to shampoo the seats in order to Scotchgard them. This was a Saturday and we were told we could pick it up Monday around 5pm. I had to get a ride from down by Solon Springs to go pick up my car. When we arrived, the outside of the car looked washed. The interior looked as if it had not been touched. There was still dust, crumbs and stains all around the car. In the pocket on the back of the passenger seat there was a literal bag of garbage still stuffed in it! I pointed this out to the salesman and he dove in there, grabbed it out and made some lame excuse as to why this would still be in there. I was very disappointed by this and told him that I thought a detailing would be much better than this. He agreed and said he would be telling the manager about what a poor job their detailer was doing, but never offered to fix this for me. Since my Husband thought I was overreacting (its a used car - yeah a $24000 used car) I drove away with it very unhappy. 5 minutes later I picked my sister and mom up for dinner. My sister immediately looked in that same pocket on the back of the seat and found chewed up, spit out sun flower seed shells!!! So disgusting. I took the car back to the dealership that night and showed another salesman my issues (mine had gone home for the day). Although he agreed it was not okay, he also gave me excuses that sometimes they have so many cars go through in a day the detailer skips some things. I can maybe buy that line IF I had not PAID them $700 extra dollars to clean my car! He took my name and number and said someone would call me the next day. I did not hear from them the next day so I called and spoke to the Used Car Manager. Again, he seemed to agree that the seed shells were not okay, but said to me, "what would you like me to do?" What would I like you to do???? CLEAN MY CAR. He scheduled me for about a week later for another full detailing. I had to leave work to get my car their in the morning and although they did give me a free rental, I still had to pay my gas (even though this was their fault). Again, I go up to get my car for the second time. The only thing they did was remove the seed shells and wash the outside again. I am still not sure they Scotchgarded the seats. Every speck of dust and crumb was still there. The sun was shining very bright so when I looked at the back of the seats to see if they were at least clean, it looked like they were. Once I got home in different lighting it was clear the seats were not clean. As a female (by myself) being told by a Male salesman that he and the used car manager AND the owner HOWIE KRENZEN went to the detail place to make sure my car was done well and apparently all of them thought this was a spectacular cleaning job; I was dumbfounded. I started to question myself if maybe I was just too picky. I got in my car and drove away. I went and bought some Armorall wipes at a Dollar General and one 50 cent wipe did a better job on the interior of my car than 2 supposed detail jobs. I do not doubt in my mind now that they gas lighted me into thinking I was expecting too much from a "used car". By the way, it was a 2017.5 - about 9 months old. Cost me $24,000 in the end and they stole the joy of having a new car away from me. I will never recommend them.Read More
"Best Sales Associate Ever!"- JR
My wife and I had Nate Greene help us through a purchase a used vehicle process. How refreshing to work with a considerate young man who believes in putting the customer first. Although we did not buy that day we will certainly look for Nate our next time. Thank You Nate!Read More
"Unethical Scott Krenzen and Team - Scam Artists"- NoTimeForUnethicalDealer
Most unprofessional and unethical car buying experience I have ever had in my life. Company culture is to never be accountable or take blame for anything. There is a fine line between arrogance and ignorance and this dealership is right on the fence. Incompetent sales staff couldn't properly transfer tag from other vehicle and cost to do it ourselves was never reimbursed. After we purchased our 2016 Honda CR-V in late 2016, we referred a family member who bought the exact same model vehicle a week later for $500 less than we paid from the admission of my family member but until I confronted the sales manager with the facts, they weren't willing to admit that. Here's the real kicker, Honda outfitted their 2016 CR-V (all models) with in-dash technology that was 4 years out of date at the time of sale. The technology will NOT interface to iPhones that are iPhone 6 or later. All Krenzen wanted to do is blame Honda when they should have known full well the vehicles they were selling had old technology. Krenzen would not take ownership and work with us to remedy this; just indicating they were waiting for Honda to provide direction when Honda indicated they did provide direction and that was for Krenzen to replace the technology under a warranty issue. Run....don't walk from this dealershipRead More
"No place better than Krenzen"- Pleased
We have purchased all our vehicles from Krenzen and Gary Cora has been outstanding in keeping our family happy with our purchases! Service is outstanding ! Best place to purchase from! Cindy L.Read More
"Waste of time"- iFox8
I went to the dealership three times, at there request, with check in hand to purchase a new vehicle. However the prices are high and Krenzen expects MSRP for there vehicles. They use many tactics to justify the higher cost, when the same vehicle can be purchased for less at other locations such as Ashland's Honda Dealer. Personally I just felt that they didn't want to sell me a car. Guess I'm not the Honda type. I explored all the surrounding dealerships for GM, Ford, Toyota, Mazda, and Subaru. Every location attempted to earn my sale, and were motivated to sale to me. For the same Honda vehicle I wanted I was able to find multiple better prices for it in the surrounding area. Nice dealership but a waste of time unless you don't mind paying more for the same vehicle.Read More
"Best Dealership In Town"- Mjanousek
My family has been buying vehicles from Krenzen since the '70s and I have been a customer myself for the last 5 years. I have shopped around myself and always felt hassled or pressured into buying and then pushed into something I didn't want at other dealerships. At Krenzen they let me test drive the vehicles to get a real feel for them and know that it's exactly what I want. They have a HUGE selection of all makes, models, and trim packages, but best of all... They're not worried about their commission because it's not commission based!! I will follow in the family footsteps and encourage you to try them out on your next vehicle purchase. You won't be disappointed.Read More


text:
- Name
- Lipegfilgrastim
- Accession Number
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Other protein based therapies
- Description
Lipegfilgrastim, previously known as XM22, is a pegylated, recombinant granulocyte colony-stimulating factor (G-CSF) that was synthetized using a highly site-specific glycoPEGylation technology 2. It is used as an alternate to Pegfilgrastim for prophylactic use in cancer patients receiving chemotherapy and at risk for developing chemotherapy-induced neutropenia. Since July 2013, lipegfilgrastim is marketed by the EMA as Lonquex for subcutaneously injection, where it is administered once following cytotoxic chemotherapy for each chemotherapy cycle in adult patients being treated with cytotoxic chemotherapy for malignancy. It aims to reduce the duration of neutropenia and the incidence of febrile neutropenia.
Neutropenia and febrile neutropenia (FN) are frequent and potentially fatal complications that occur from myelosuppressive anticancer treatments 2. Severe chemotherapy-induced neutropenia and febrile neutropenia significantly increases the risk for life-threatening infection and sepsis. Granulocyte colony-stimulating factors (G-CSFs) were introduced in the 1980's to the clinical setting to stimulate neutrophil proliferation and differentiation, thereby reducing the duration and severity of chemotherapy-induced neutropenia 2. Lipegfilgrastim is a covalent conjugate of Filgrastim with a single methoxy polyethylene glycol (PEG) molecule via a carbohydrate linker consisting of glycine, N-acetylneuraminic acid and N-acetylgalactosamine 5. The average molecular mass of lipegfilgrastim comprises 18,798 Da for Filgrastim, 203 Da for GalNAc, 338 Da for glycylsialic acid and approximately 20,000 Da for PEG 6. PEG moiety protects the active molecule from enzyme degradation, which allows longer half-life of drug and less frequent dosing-schedule in addition to acceptable safety and efficacy profile 2.
- Protein structure
- Protein chemical formula
- C866H1372N226O258S9*(C2H4O)n
- Protein average weight
- 39000.0 Da (glycoPEGylated, approximate)
- Sequences
>Lipegfilgrastim sequence MTPLGPASSLPQSFLLKCLEQVRKIQGDGAALQEKLCATYKLCHPEELVLLGHSLGIPWA PLSSCPSQALQLAGCLSQLHSGLFLYQGLLQALEGISPELGPTLDTLQLDVADFATTIWQ QMEELGMAPALQPTQGAMPAFASAFQRRAGGVLVASHLQSFLEVSYRVLRHLAQPDownload FASTA Format
- Synonyms
- Not Available
- External IDs
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing EndUnlock Additional Data Lonquex Injection, solution 6 mg Subcutaneous Sicor Biotech Uab 2013-07-25 Not applicable Lonquex Injection, solution 6 mg Subcutaneous Sicor Biotech Uab 2013-07-25 Not applicableAdditional Data Available
- Application NumberApplication Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.Learn more
- Product CodeProduct Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.Learn more
- Categories
- Adjuvants, Immunologic
- Alcohols
- Amino Acids, Peptides, and Proteins
- Antineoplastic and Immunomodulating Agents
- Biological Factors
- Carbohydrates
- Colony-Stimulating Factors
- Compounds used in a research, industrial, or household setting
- Cytokines
- Ethylene Glycols
- Glycoconjugates
- Glycols
- Glycoproteins
- Granulocyte Colony-Stimulating Factors
- Hematopoietic Cell Growth Factors
- Intercellular Signaling Peptides and Proteins
- Macromolecular Substances
- Pegylated agents
- Peptides
- Polymers
- Proteins
- CAS number
- 1117844-87-7
- Indication
Indicated for the reduction in the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukaemia and myelodysplastic syndromes) 5.
- Associated Conditions
- Pharmacodynamics
Mimicking endogenous granulocyte colony-stimulating factors, lipegfilgrastim enhances the number and function of circulating neutrophils by binding to endogenous G-CSF receptors. A small increase in monocyte and/or lymphocyte counts may also be observed 5. Following a single subcutaneous dose administration of 100 μg/kg, lipegfilgrastim resulted in a significant increase in neutrophilic granulocyte and large unstained cell counts 6. G-CSF also increases the antibacterial activities of neutrophils including the phagocytosis 5. Due to structural similarity between lipegfilgrastim and pegfilgrastim, G-CSF receptor binding was equivalent between two molecules 2. However, lipegfilgrastim showed greater time-dependent resistance to neutrophil elastase degradation and greater retention of activity than pegfilgrastim 2.
- Mechanism of action
Endogenous granulocyte colony-stimulating factor (G-CSF) is a glycoprotein that stimulates neutrophil progenitors. It is produced mainly by monocytes, fibroblasts and endothelial cells to promote the development of neutrophils and increase their proliferation and maturation 4. Subsequently, G-SCF stimulates the release of matured neutrophils from the bone marrow storage pools into the peripheral blood to enhance their function 5,4. Via binding to to the human G-CSF receptors, lipegfilgrastim activates the receptor signalling pathway as a growth factor to stimulate proliferation of haematopoietic progenitor cells and their differentiation into mature cells, and promote subsequent release into the peripheral blood 5. This stimulatory effect of lipegfilgrastim may extend to other single lineage and multilineage progenitors and pluripotent haematopoietic stem cells 5. The presence of the PEG moiety in lipegfilgrastim decreases the plasma clearance and extends the drug's terminal elimination half-life, allowing for less frequent dosing 1.
Target Actions Organism AGranulocyte colony-stimulating factor receptoragonist Humans
- Absorption
In studies of healthy volunteers receiving a single subcutaneous injection of 6 mg of lipegfilgrastim, the peak plasma concentration of lipegfilgrastim was reached after a median of 30 to 36 hours 5. Based on its molecular weight, lipegfilgrastim is believed to be primarily absorbed via the lymphatic system then drained into the vascular system 7. Peak concentration and area under the curve, indicating full bioavailability, was lower in injection site of the thigh compared to subcutaneous injection in the abdomen and in the upper arm, with differences among the injection sites being the greatest in males compared to female subjects 5.
- Volume of distribution
Lipegfilgrastim has a weight-dependent volume of distribution of 70 mL/kg, indicating minimal distribution beyond the lymphatic or vascular system 7.
- Protein binding
- Not Available
- Metabolism
Lipegfilgrastim is metabolised via intra- or extracellular degradation by proteolytic enzymes 5. Following binding to the G-CSF receptors, it is proposed to be internalized by neutrophils via a non-linear process, and then undergoes degradation within the cell by endogenous proteolytic enzymes. Alternatively, the linear pathway is likely due to extracellular protein degradation by neutrophil elastase and other plasma proteases 5.
- Route of elimination
Lipegfilgrastim undergoes two distinct clearance pathways: linear pathway composed of degradation by proteolytic enzymes and non-linear pathway involving neutrophil-mediated clearance 7. The elimination pathway by neutrophil-mediated clearance is saturated at higher doses 3. Lipegfilgrastim and its degraded fragments may undergo renal clearance 5.
- Half life
The average terminal half-life ranged from approximately 32 to 62 hours after a single subcutaneous injection of 6 mg lipegfilgrastim in healthy individuals 5.
- Clearance
In a phase 1, multinational, open-label, single-arm study of paediatric patients with Ewing family of tumors or rhabdomyosarcoma treated with myelosuppressive chemotherapy, the mean apparent clearance (CL/F) was approximately 71 mL/h, 120 mL/h, and 116 mL/h for age groups of 2-6 years, 6-12 years, and 12-18 years, respectively 3.
- Toxicity
In safety pharmacological studies in rats and dogs, lipegfilgrastim was well tolerated at a single subcutaneous dose of 10 mg/kg. In the renal excretion study in rats, an intravenous dose of 250 μg/kg was well tolerated 6. While mutagenicity and genotoxicity studies have not been conducted with lipegfilgrastim, G-CSF has been reported to stimulate tumour growth and intratumoural vessel density in animal tumour models 6.
- Affected organisms
- Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.Learn more
Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.Learn more
Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.Learn more
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug InteractionUnlock Additional Data Abicipar Pegol The therapeutic efficacy of Lipegfilgrastim can be decreased when used in combination with Abicipar Pegol. Aldesleukin Aldesleukin may increase the myelosuppressive activities of Lipegfilgrastim. Alemtuzumab Alemtuzumab may increase the myelosuppressive activities of Lipegfilgrastim. Altretamine Altretamine may increase the myelosuppressive activities of Lipegfilgrastim. Amsacrine Amsacrine may increase the myelosuppressive activities of Lipegfilgrastim. Antihemophilic Factor (Recombinant), PEGylated The therapeutic efficacy of Lipegfilgrastim can be decreased when used in combination with Antihemophilic Factor (Recombinant), PEGylated. Arsenic trioxide Arsenic trioxide may increase the myelosuppressive activities of Lipegfilgrastim. Azacitidine Azacitidine may increase the myelosuppressive activities of Lipegfilgrastim. Belinostat Belinostat may increase the myelosuppressive activities of Lipegfilgrastim. Bendamustine Bendamustine may increase the myelosuppressive activities of Lipegfilgrastim.Additional Data Available
- Extended DescriptionExtended Description
Extended description of the mechanism of action and particular properties of each drug interaction.Learn more
- SeveritySeverity
A severity rating for each drug interaction, from minor to major.Learn more
- Evidence LevelEvidence Level
A rating for the strength of the evidence supporting each drug interaction.Learn more
- ActionAction
An effect category for each drug interaction. Know how this interaction affects the subject drug.Learn more
- Food Interactions
- Not Available
- General References
- Buchner A, Lammerich A, Abdolzade-Bavil A, Muller U, Bias P: Lipegfilgrastim: pharmacodynamics and pharmacokinetics for body-weight-adjusted and 6 mg fixed doses in two randomized studies in healthy volunteers. Curr Med Res Opin. 2014 Dec;30(12):2523-33. doi: 10.1185/03007995.2014.962131. Epub 2014 Sep 25. [PubMed:25251999]
- Guariglia R, Martorelli MC, Lerose R, Telesca D, Milella MR, Musto P: Lipegfilgrastim in the management of chemotherapy-induced neutropenia of cancer patients. Biologics. 2016 Jan 22;10:1-8. doi: 10.2147/BTT.S58597. eCollection 2016. [PubMed:26858523]
- Belogurova MB, Kizyma ZP, Garami M, Csoka M, Lamson MJ, Buchner A, Bias P, Lammerich A: A pharmacokinetic study of lipegfilgrastim in children with Ewing family of tumors or rhabdomyosarcoma. Cancer Chemother Pharmacol. 2017 Jan;79(1):155-164. doi: 10.1007/s00280-016-3216-2. Epub 2016 Dec 16. [PubMed:27986986]
- 25. (2012). In Rang and Dale's Pharmacology (7th ed., pp. 315). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
- European Medicines Agency (EMA) Summary of Product Characteristics: Lonquex (lipegfilgrastim) [Link]
- Australian Public Assessment Report for Lipefilgrastim (rbe) [Link]
- Therapeutic Goods Administration (TGA) product Information: Lonquex [Link]
- External Links
- Not Available
- ATC Codes
- L03AA14 — Lipegfilgrastim
- Download (20.2 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 1 Completed Not Available Pharmacodynamics / Pharmacokinetics 1 1 Completed Supportive Care Ewing Family of Tumors, Rhabdomyosarcoma 1 1, 2 Recruiting Treatment Malignant Lymphomas / Multiple Myeloma (MM) 1 3 Completed Treatment Aggressive B Cell Non-Hodgkin Lymphomas at High Risk for R-CHOP-21-induced Neutropenia 1 Not Available Completed Not Available Breast Cancer 1
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage forms
Form Route Strength Injection, solution Subcutaneous 6 mg
- Prices
- Not Available
- Patents
- Not Available
- State
- Liquid
- Experimental Properties
- Not Available
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Receptor activity
- Specific Function
- Receptor for granulocyte colony-stimulating factor (CSF3), essential for granulocytic maturation. Plays a crucial role in the proliferation, differientation and survival of cells along the neutroph...
- Gene Name
- Uniprot ID
- Uniprot Name
- Granulocyte colony-stimulating factor receptor
- Molecular Weight
- 92155.615 Da
Drug created on June 23, 2017 14:37 / Updated on December 02, 2019 09:52


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Customer Service Starts in the Office
In the Chapman office we have several people that strive every day to provide customers with the level of service with integrity and professionalism that you've come to expect from Chapman Heating and Air.
Sarah and Gene are our Customer Service Representatives, they make sure every phone call or walk in customer is taken care of professionally and in a timely manner. They are the first faces you see when walking into the Chapman office. Sarah's favorite hobby is camping, and Gene enjoys a good game of golf.
Heidi D. coordinates all of the installation customers, and Shana coordinates service and maintenance technicians. With the two of them in charge you can be certain that the technicians know exactly where they are going every day, and that their days run smoothly. Heidi can be found out in her garden, and Shana loves making some delicious food.
Another member of the office team is Alan. Alan is known as our Operations Manager, and he is the go-to man when a customer or service technician has a tough question. His favorite hobbies are hunting and fishing.
The next three guys might have desks, but they are out in the field with our customers just as much as the technicians! Our Comfort Advisors Terry and Thad visit customers daily to provide them with proposals on system replacements and new units. They are very knowledgeable on any rebates offered by Columbia, electric companies, or the manufacturer to ensure you are getting the best value. Terry and Thad both enjoy spending time with their families on the weekends.
Tony is our Home Performance Specialist, with his expertise he certifies that our customers' homes are as energy efficient as possible, makes recommendations to help them become more efficient, and provides information on rebates and tax credits that might be available to the homeowner. Tony enjoys working on his house and is a regular triathlon runner.
The last and newest member of the office team is Samantha who keeps the marketing department running smoothly and coordinates all things fun in the office. Samantha loves painting and gardening.
From our customer service representatives to our technicians, everyone works together to bring you the best service experience possible, after all our number one goal from Grandpa to the third generation is: Take Care of the Customer!


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New market research report helps analyze the Periodontal Dental Services market on a global basis and also offers forecast and statistics in terms of revenue for the anticipated forecast period. This research study offers a detailed overview of the market dynamics that are expected to affect the overall industry in the coming few years. In addition, the study explains the impact of the key factors on the development and growth of the global market through the forecast period.
Get Sample copy of this Report: https://www.researchnreports.com/request_sample.php?id=119269
To offer a clear understanding of the Global Periodontal Dental Services market, several questions have been addressed in the research study concerning the growth of the global market. It is also been discussed with respect to projected growth rate of the global market in the near future. Also, depending on the ongoing trend of the market, the region which is anticipated to witness high growth in the next few years is studied in detail.
Companies Profiled in this Report includes, Coast Dental, Pacific Dental Services, Q & M Dental, Apollo White Dental, Aspen Dental, Brighton Dental Group, BPI Dental,, IMI Clinic, Highland Dental Care, Parkway Health, St. Claire Perio, St. Helena Dental Group, Sun Lakes Dental, Burlingame Dentistry
Periodontal Dental Services Market Segmentation by Type:
- Surgical Dental Services
- Non-surgical Dental Services
Periodontal Dental Services Market segment by Application:
- Hospitals
- Dental Clinics
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The report provides information on the technological advancements that are bound to take place in the coming years or are currently taking place in the market. Furthermore, the opportunities and threats faced by the main player's dominant in the Global Periodontal Dental Services market have been highlighted. This report covers the market from the bottom line, starting from its definition. Later, it segments the market on various criteria to give a depth of understanding on the various product types and pricing structures and applications. Each and every segment is examined carefully by factoring in revenue and market size in order to understand the potential of growth and scope.
Table of Contents
Global Periodontal Dental Services Market Research Report
Chapter 1 Periodontal Dental Services Market Overview
Chapter 2 Global Economic Impact on Industry
Chapter 3 Global Market Competition by Manufacturers
Chapter 4 Global Production, Revenue (Value) by Region
Chapter 5 Global Supply (Production), Consumption, Export, Import by Regions
Chapter 6 Global Production, Revenue (Value), Price Trend by Type
Chapter 7 Global Market Analysis by Application
Chapter 8 Manufacturing Cost Analysis
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Molecular properties generated using the CDK
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|Summary of Clinical Use
|SB-681323 has been assessed to Phase II in clinical trial for indications including chronic obstructive pulmonary disease, rheumatoid arthritis and neuropathic pain, although there are no currently active trials (as of Nov 2014). Click here to view the list of completed SB-681323 trials at ClinicalTrials.gov.
|Mechanism Of Action and Pharmacodynamic Effects
|The molecular target of dilmapimod is p38 MAPK.


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Jayme Fraser melds people-focused narratives, investigative reporting and interactive graphics to evaluate social and political issues. She rarely travels without her camera, documenting adventures throughout the northwest.1 2\ Buckle-Down Nick 90's Rewind 16-Character Poses Navy bluee Breakaway Cat Collar, 1 2 x 6-9 Small.
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In December 2017, Jayme was selected for the inaugural ProPublica Local Reporting Network and will spend 2018 working on an investigative project for the Malheur Enterprise in eastern Oregon. The first story tracked Charles Longjaw's trail of crime over three decades, including while under state supervision, and examined Coffee Dot M (45x35x32cm) Coffee Dot M (45x35x32cm) Winter Warm Foldable Non-Slip Outdoor Pet Kennel Cozy Dog House Cat Sofa Puppy Bed (M (45x35x32cm), Coffee Dot) despite warnings he was dangerous.
Before that, she was a state government, special projects and education reporter for Lee Newspapers of Montana.
In the fall of 2017, she co-taught an investigations class at the University of Montana School of Journalism with Professor Joe Eaton. It was a first-time collaboration with a professional partner, the Missoulian. They mentored undergraduate and graduate students as they analyzed why Montana has one of the highest rates of drug-exposed births and how the state failed by several measures to help pregnant women who used drugs.
In 2015, she was named an KESS InHouse BarmalisiRTB Snatch orange Yellow Digital Pet Bowl, 7 Diameter as part of a Houston Chronicle team that investigated the jail suicide of Sandra Bland after a questionable traffic stop. The reporting forced state regulators to change how jails screen inmates, leading to a drastic reduction in deaths. Other projects as a writer and videographer won Jayme top recognition in the Society of Professional Journalists Region 10 Mark of Excellence Awards for three consecutive years. Large 30\ Kess InHouse Iris Lehnhardt color Play Fleece Dog Bed, 30 by 40-Inch that was named a national runner-up examined the questionable science and poor defense in a local "shaken baby" conviction. Her reporting caught the attention of the Montana Innocence Project, which successfully petitioned for exoneration. Wilkes was freed in the summer of 2018, although prosecutors say they might seek a new trial.
Jayme graduated from Erva PH5 Portal for Western blueebird Galvanized Steel, Tan Finish after studying multimedia storytelling and leading the Derby House Pro Combo Fleece Rug 4ft3 bluee Jewel Freesia.The independent campus news organization consistently broke news about the campus' failure to properly handle rape reports and a high-profile case involving football players that eventually triggered two federal investigations. She also reported for the school's Native News project as a writer and a photographer, exploring policies that affect the availability of plants for traditional uses and how the cost of transportation affects economic opportunities in one of America's most remote communities.
Jayme was a Houston Chronicle government reporter and Khaki Pet Bag Backpack Pet Backpack Collapsible Canvas Carrier Portable Traveler Handbag Transparent Large Space Breathable Comfortable For Out Door Hiking Shopping Travelling Carriers Outdoor for Cat and after internships with Encore Finest Collection Dog Pouch in Jelly 5 x 100g (PACK OF 4) metro desk, the politics team at A Dog Leash Retractable leashes for Medium Dogs & Small Dogs Hooks Long Harness Cord Hooks Handles Breed Waist golden Retriever 5FT, the bluee Medium (Neck 14\ bluee Medium (Neck 14\ azuza Leather Dog Collar, Basic Padded Leather Pet Collars Spiked & Bones Studded Dog Collars & for Puppy Small Medium Large Dog Pink, bluee, Black, Red and Hexiansheng Cat Climb Trees Cat Tree Pet Plush 40 40 75cm. Jayme reported on the 2011 Montana State Legislature for a no-charge news service to bring daily and enterprise reporting to the state's smallest community newspapers. She also occasionally works under contract for independent book publishers and authors as a copy editor, typesetter and designer for both traditional and e-book formats.
When she's not tapping a keyboard or brandishing a recorder, Jayme roots for the Portland Timbers with the (10 Pack) Ancol Comfort Mesh Dog Harness Red Medium, a regional supporters group that directs its passion for the beautiful game into a reason to do good in the community. She also loves playing cribbage with her husband, cuddling with her dorky green cheek conures, watching movies, Black Tan 30X32 Black Tan 30X32 Professionals Choice Ortho-Sport Anza Felt Pad, and baking pies.
If you would like to hire Jayme for freelance work, email Cat Scratch Tree 100CM Grey She also is interested in job opportunities that would start after December 2018.


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J.D. Martinez and the Boston Red Sox keep piling up big offensive numbers – not to mention wins – against the Los Angeles Angels.
Martinez hit his major league-leading 25th home run http://www.carolinapanthersteamonline.com/greg-little-jersey , Rafael Devers delivered a tiebreaking double and the Red Sox beat the skidding Angels 9-6 on Wednesday night after squandering a six-run lead.
Boston (54-27) moved into first place in the AL East, a half-game ahead of the rival New York Yankees. After finishing their series with the Angels on Thursday night, the Red Sox play three games at Yankee Stadium this weekend.
The homer by Martinez capped a six-run second for the Red Sox, who won for the fifth time in six games. Eduardo Nunez and Sandy Leon also went deep in the inning. Boston improved to 5-0 against the Angels this season and has outscored them 45-10 with 18 homers and a .363 batting average.
It's the most homers by any club in a season series of six games or fewer, according to the Red Sox.
"I don't know. That's just what it is, really. There's no one explanation," Martinez said. "Maybe we just match up well against them."
Martin Maldonado launched a three-run homer and Ian Kinsler had a solo shot for the Angels, who lost their fifth straight and 12th in 16 games.
Los Angeles reliever Jake Jewell was carted off the field with what appeared to be a gruesome injury to his right ankle after covering the plate on a run-scoring wild pitch in the eighth.
"He's getting evaluated, I think, at Massachusetts General," Los Angeles manager Mike Scioscia said. "Hopefully we'll get an idea of what's happening sometime tonight."
Angels star Mike Trout went 1 for 4 as a sprained right index finger kept him as the designated hitter for the eighth consecutive game.
Devers doubled off reliever Jose Alvarez (3-3) in the seventh, putting Boston back in front 7-6, and scored on Leon's single in a game that took 4 hours.
"It was a weird game Will Grier Jersey , slow pace," Boston manager Alex Cora said. "I'm glad we won the game. Not a pretty game to watch."
Matt Barnes (2-2) worked a scoreless inning. Craig Kimbrel got four outs for his 23rd save, his first of more than three outs this season.
The Angels trailed 6-0 and looked as though they were in line for another lopsided loss to Boston before they charged back with a run in the fifth on Kinsler's homer, three in the sixth on Maldonado's shot and two in the seventh.
"We battled back and got in the game. We'll keep battling," Scioscia said. "But, at some point, obviously we need to put both ends together and get the pitching we need, get some early runs and get the game on our terms and we're going to start to do things the way we can."
Andrelton Simmons' RBI double off reliever Joe Kelly tied it.
Martinez's shot went over the Green Monster in left-center, raising his big league-best RBI total to 64. In his first season with Boston, the slugger has the most home runs in Red Sox history before the end of June.
Nunez hit Andrew Heaney's first pitch of the second into the center-field bleachers. Leon drove an inside fastball off a billboard above the Green Monster.
Boston starter Rick Porcello gave up four runs in 5 2/3 innings. Heaney was tagged for six runs in 3 1/3 innings.
Angels: INF Zack Cozart got a second opinion on his left shoulder after experiencing continued discomfort and plans to have surgery in Los Angeles soon to repair a torn labrum, the team said. … Scioscia said two-way rookie star Shohei Ohtani (sprained elbow ligament) will be re-evaluated Thursday. Three weeks ago, Ohtani's elbow was injected with platelet-rich plasma and stem cells as he tries to avoid Tommy John surgery.
Red Sox: Cora said 2B Dustin Pedroia and knuckleballer Steven Wright will see Dr. Riley Williams III when the club is in New York to play the Yankees this weekend. Both are on the 10-day DL with left knee inflammation and had surgery performed by Dr. Williams. "Maybe we can do something differently as far as the treatments," Cora said about Pedroia http://www.carolinapanthersteamonline.com/christian-miller-jersey , who has played in just three games since offseason surgery. … Drew Pomeranz threw a simulated game and Cora said the left-hander could start a rehab assignment with Triple-A Pawtucket on Monday.
The Red Sox signed infielder Brandon Phillips to a minor league deal. The 36-year-old veteran has played with five teams over 16 seasons.
Angels: RHP Jamie Barria (5-3, 3.40 ERA) is slated to pitch the series finale Thursday. It will be his first career start against Boston.
Red Sox: LHP Brian Johnson (1-2, 4.50) takes Wright's turn in the rotation after he went on the disabled list Tuesday.
NASHVILLE, Tenn. (AP) — The Tennessee Titans spent the second day of the draft addressing their issues on offense.Tennessee took Mississippi wide receiver A.J. Brown in the second round Friday with the 51st overall pick and added Charlotte guard Nate Davis in the third round with the 82nd selection. The moves provide an additional weapon and better protection for quarterback Marcus Mariota as he enters the final year of his contract."As a rookie, I've got to come in and build that trust with" Mariota, Brown said. "That's going to be big. With him, he's going to get a complete receiver. Anything he needs, I'm going to be there."Tennessee needed to bolster an offense that scored just 19.4 points per game last season. The Titans used their first-round pick Thursday on Mississippi State defensive tackle Jeffery Simmons and focused on defense in their 2018 draft.The only offensive player Tennessee drafted last year was Washington State quarterback Luke Falk, who went in the sixth round and is no longer on the Titans' roster.Brown should provide an immediate boost.He set Ole Miss single-season records in catches (85) and yards receiving (1,320) while earning Associated Press All-America third-team honors last season. The 6-foot Brown left Ole Miss with a school-record 2,984 career yards receiving while showcasing a versatile skill set that combines size and speed."I do a little bit of everything, honestly," Brown said.Corey Davis Jordan Scarlett Jersey , the No. 5 overall pick in the 2017 draft, led the Titans with 891 yards receiving and four touchdowns last season. But the Titans didn't have anyone else with as many as 500 yards receiving.Brown could help in that regard. He considers himself a quality route runner and a student of the game."You have to study the game," Brown said. "You just can't be a fast guy or a big guy. You've got to know the ins and outs. You have to know defenses and things like that. You've got to watch football. I watch football 24/7. I watch Julio Jones run routes all the time."The Titans haven't had a 1,000-yard receiver since Kendall Wright caught 94 passes for 1,079 yards in 2013. They added to their receiving corps by signing free agent Adam Humphries but wanted to add more targets for Mariota.Titans coach Mike Vrabel said Brown made a strong impression during his visit with team officials."You just got a sense he was a serious, professional football player," Vrabel said. "It seemed like he wasn't about the glitz and the glamour. He kind of just sat down and talked. It felt like we were having a conversation with a guy that was already a pro football player in just his maturity level and how he approached his daily routine, the game, how he practiced, how he prepared."Brown said he had a pretty good idea the Titans were interested in him."This was one of the teams I thought was going to take me," Brown said. "I thought a little sooner, but God works in mysterious ways."Nate Davis, who is 6-3 and 311 pounds Greedy Williams Jersey , was a starting tackle at Charlotte last season after spending three years as a starting guard. He should help the Titans upgrade an offensive line that allowed 47 sacks last season.Tennessee wanted to improve the interior of its line to open up more running room for Derrick Henry, who came on strong late last season and ended up rushing for 1,059 yards and 12 touchdowns.The Titans signed Rodger Saffold away from the Los Angeles Rams to fill one starting guard position, but the other guard spot remains up for grabs. Davis said his goal is to win that job."That's my goal, to come in and earn the respect of the locker room, the older guys and the vets like that, and just do what I do," Davis said. "And hopefully I can earn that spot."The Titans have one pick each in the fourth, fifth and sixth rounds Saturday. They could still use an edge rusher to provide depth at that spot after the retirement of Brian Orakpo, though they have signed former Miami Dolphins defensive end Cameron Wake.


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@FierceMedDev: Thermo soars after Life Tech deal and dials up its expectations. Story | Follow @FierceMedDev
@VarunSaxena2: Federal court postpones Edwards' block of Medtronic's CoreValve. More | Follow @VarunSaxena2
@EmilyWFierce: Cleveland startup won JDRF support for its rapid-acting insulin analog for Type 1 diabetes. News | Follow @EmilyWFierce
@MichaelGFierce: X-ray-activated nanoparticles release #cancer-killing light deeper into tissue. More from FierceDrugDelivery | Follow @MichaelGFierce
> Illumina's ($ILMN) revenue jumped 27% to $421 million in the first quarter, and net income came in at $60 million, beating a $23 million loss from the same period last year. Results
> Cook Medical has launched its Instinct Endoscopic Hemoclip around the globe, marketing a device designed to stop bleeding in the gastrointestinal tract. News
> Siemens ($SI) won FDA clearance for Somatom Force, a computed tomography imaging device. Release
Biotech News
@FierceBiotech: Shooting for IPO glory, Alder cites trial success with migraine drug. More | Follow @FierceBiotech
@JohnCFierce: Amgen beats a path to the FDA, looking for an early approval of leukemia drug. Story | Follow @JohnCFierce
@DamianFierce: BMY pal Alder hit the mark in a migraine trial, good news on the eve of its IPO. News | Follow @DamianFierce
@EmilyMFierce: TB drug could be basis for class of broad-spectrum treatments. More from VaccinesNewsDaily | Follow @EmilyMFierce
> Kala reels in $22.5M to get its next-gen eye drops into PhIII. News
> Spectrum touts PhII cancer data, plans NDA. Item
> Allergan fashions a poison pill as raiders at Valeant promise to gut R&D. Story
Pharma News
@FiercePharma: Google exec figures pharma could go viral on YouTube--if it tried. More from FiercePharmaMarketing. | Follow @FiercePharma
@TracyStaton: $16B deal for GlaxoSmithKline oncology meds turns Novartis into cancer heavyweight. Story | Follow @TracyStaton
@EricPFierce: Gilead turns in eye-popping results because of huge sales of Sovaldi, $2.3B in Q1 sales for the hep C drug. News | Follow @EricPFierce
@CarlyHFierce: Big Pharma sees danger, not safety, in U.S. FDA's new social media guidance. Article | Follow @CarlyHFierce
> Payer revolt notwithstanding, Gilead's Sovaldi earns crown as fastest drug launch ever. News
> Amgen's $4.5B in Q1 sales lags estimates, thanks to slow-selling Enbrel. More
> Biogen sales leap 50% on blockbuster-level Tecfidera sales. Story
> NICE rejects Roche's hot new breast cancer drug Kadclya, then invites negotiations. Article
Drug Delivery News
> Hydrocarbon double-stapling of peptides a new trick in fight against viruses. Report
> Mylan launches first generic transdermal contraceptive patch. News
> X-ray-activated nanoparticles release cancer-killing light deeper into tissue. Article
> Stanford team finds that nanotubes catch a ride with immune cells to reach tumors. More
> DNA nanocages that act like viruses bypass the immune system to deliver drugs. Story
> ProNAi, with delivery tech licensed from Marina, snags $59.5M for cancer trials. Item
Diagnostics News
> MDxHealth broadens reach of prostate cancer Dx with new U.S. PPO deal. News
> Investors initially respond well to Abbott's diagnostics gains. More
> Cepheid's 2014 Q1 produced Dx sales hikes but also more losses. Report
> UW-Madison team concocts asthma blood Dx that could work before symptoms appear. Story
> KineMed, with IPO in sight, joins global diabetes biomarker research project. Article
Pharma Marketing News
> Google exec figures pharma could go viral on YouTube--if it tried. News
> Big Pharma sees danger, not safety, in FDA's new social media guidance. Story
> It's official: Gilead's Sovaldi zooms past previous records with fastest-ever drug launch. Article
> Allergan sales force key to Valeant chief's plans for post-merger growth. Report
> Doc offices that nix free samples cut way back on branded scripts: JAMA study. More
> Lilly nabs FDA approval for its blockbuster cancer hopeful ramucirumab. Item


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text: Any seniors interested in learning new drawing and painting techniques can join the Portage County Senior Center group on the second and fourth Tuesdays of each month at 10 a.m. for an instructor-led class. This is a free class and all seniors are welcome, whether a novice or experienced painter. The senior center is located at 705 Oakwood St. (Floor G) in Ravenna. For more information, call 330-297-3456.


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The Loathing Tuesdays
February 15th, 2005
Tuesday is my absolute least favourite day of the week. Don't ask me why. It just is. (sounds like religious reasoning, doesn't it) I had band today for five hours, and at least three of those hours stunk, like what comes out of the spit valve of a tuba after a frat party.
I'm also giving up all my spare time, which is only about an hour when you factor in practice, school, eating, sleep, and homework, to playing Civilization 2, a really old school turn-based computer game. It's really complex and interesting yet doesn't take up too many computer resources. I'm a pacifist and a secularist, but there's just something really compelling about having a fundamentalist government and forcing your rule on the entire world.


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2 Reasons To Replace Your Existing Roof With Copper Tiles
Replacing your existing roof is a great way to improve your home, mostly because of the many ways it can benefit you. Two reasons to replace your existing roof with copper tiles are to save money and make your home safer. Save Money Copper tiles can save you money in a variety of ways, with one of the biggest ways being that they can lower your utility bills. This type of roofing material lowers your utility bills in the summer by actually making your home cooler. Read More»