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Possible role of the α7 nicotinic receptors in mediating nicotine's effect on developing lung – implications in unexplained human perinatal death
Epidemiology and public health
It is well known that maternal smoking during pregnancy is very harmful to the fetus. Prenatal nicotine absorption, in particular, is associated with alterations in lung development and functions at birth and with respiratory disorders in infancy. Many of the pulmonary disorders are mediated by the interaction of nicotine with the nicotinic receptors (nAChRs), above all with the α7 nAChR subunits that are widely expressed in the developing lung. To determine whether the lung hypoplasia frequently observed in victims of sudden fetal and neonatal death with a smoker mother may result from nicotine interacting with lung nicotinic receptors, we investigated by immunohistochemistry the possible presence of the α7 nAChR subunit overexpression in these pathologies.
In lung histological sections from 45 subjects who died of sudden intrauterine unexplained death syndrome (SIUDS) and 15 subjects who died of sudden infant death syndrome (SIDS), we applied the radial alveolar count (RAC) to evaluate the degree of lung maturation, and the immunohistochemical technique for nAChRs, in particular for the α7 nAChR subunit identification. In the same cases, an in-depth study of the autonomic nervous system was performed to highlight possible developmental alterations of the main vital centers located in the brainstem.
We diagnosed a "lung hypoplasia", on the basis of RAC values lower than the normal reference values, in 63% of SIUDS/SIDS cases and 8% of controls. In addition, we observed a significantly higher incidence of strong α7 nAChR immunostaining in lung epithelial cells and lung vessel walls in sudden fetal and infant death cases with a smoker mother than in age-matched controls. Hypoplasia of the raphe, the parafacial, the Kölliker-Fuse, the arcuate and the pre-Bötzinger nuclei was at the same time present in the brainstem of these victims.
These findings demonstrate that when crossing the placenta, nicotine can interact with nicotinic receptors of both neuronal and non-neuronal cells, leading to lung and nervous system defective development, respectively. This work stresses the importance of implementing preventable measures to decrease the noxious potential of nicotine in pregnancy.
Maternal smoking during pregnancy has been associated with intrauterine growth retardation, low birth weight, neonatal morbidity and mortality, as well as an increased incidence of respiratory disorders and of an attention deficit in infants
Fetal damage caused by maternal smoking mainly result from the interaction of nicotine with nicotinic acetylcholine receptors (nAChRs)
It is well known that nAChRs regulate critical aspects of brain maturation during the intrauterine and early postnatal periods, mediating the neurochemical transmission of acetylcholine among the neurons
The knowledge of the biology of nAChRs has expanded in recent years thanks to the identification of the nAChRs also in several peripheral organs, including the lungs
Previously, we have reported a high incidence of lung hypoplasia in subjects who died of Sudden Intrauterine Unexplained Death Syndrome (SIUDS) and Sudden Infant Death Syndrome (SIDS)
Among the many cases sent to our Research Center according to the guidelines stipulated by the Italian law n.31/2006 "
Twenty-seven mothers of the SIUDS/SIDS group (45%) claimed to smoke before and during pregnancy, while the remaining 32 (55%) denied they smoked.
We included in the study a control group consisting of 24 age-matched subjects (16 fetuses and 8 newborns) in which the autopsy established a precise cause of death (specifically, respiratory infections, cardiomyopathies, sepsis in infant deaths; cardiomyopathies and chorioamnionitis in fetal deaths). Five of the 24 mothers of the control group (21%) reported a smoking habit, while 19 mothers (79%) were non-smokers.
Parents of all the victims of the study provided written informed consent to autopsy, with the Milan University "Lino Rossi" Research Center institutional review board approval.
A complete autopsy examination was carried out in every case including, in particular, an in-depth study of the brainstem and of the lungs. All organs were fixed in 10% phosphate-buffered formalin, processed and embedded in paraffin.
Brainstem examination
The brainstem was examined according to the protocol routinely applied in the "Lino Rossi" Research Center, available in our previous works
The routine histological evaluation of the brainstem was focused on the main nuclei checking the vital functions: the locus coeruleus, the Kölliker-Fuse and the rostral raphe nuclei (magnum and caudal linear nuclei) in the rostral pons/caudal mesencephalon; the retrotrapezoid, the parafacial, the superior olivary and the median raphe nuclei in the caudal pons; the hypoglossus, the dorsal motor vagus, the tractus solitarius, the ambiguus, the pre-Bötzinger, the inferior olivary, the arcuate, the obscurus and the pallidus raphe nuclei in the medulla oblongata.
In addition we performed a morphometric analysis of the main nuclei with an Image-Pro Plus Image Analyzer (Media Cybernetics, Silver Spring, Maryland, USA) in serial histological sections. The following parameters were evaluated for every nucleus: neuronal density, (number of neurons per unit area-
Lung examination
Regarding the lung examination, the main focus of the study, samples were obtained from each lobe by cutting parallel to the frontal plane and passing through the hilus. The histological examination of the routinely stained sections by hematoxylin-eosin included the evaluation in terminal lung units (i.e., portions of parenchyma distal to the last respiratory bronchioles, identifiable by an incomplete epithelial lining) of the radial alveolar count (RAC). This is a reliable index of lung maturation in intrauterine and early postnatal development established by Emery and Mithal in 1960
nAChR immunohistochemistry
Immunohistochemical methods were applied to selected histological sections of lungs in order to evaluate the expression of α7 nAChRs by using specific rabbit polyclonal antibodies (aa 22–71, Abcam cod. ab10096). Sections, after dewax and rehydration, were immersed and boiled in a Citrate Buffer solution pH 6.0 (for α3) and in TRIS-EDTA Buffer (for α7 and β2) for the antigen retrieval with a microwave oven, having first blocked endogenous peroxidase by 3% hydrogen peroxide treatment. Then, sections were incubated with the primary antibodies overnight (diluitions: 1:75 for α3, 1:500 for α7 and 1:167 for β2) in a wet chamber. Samples were washed with PBS buffer and incubated with a secondary anti-rabbit antibody and then processed with a usual avidin-biotin-immunoperoxidase technique (VECTOR LABS, Burlingame, CA). Finally each section was counterstained with Mayer's Hematoxylin and coverslipped.
A set of sections from each group of the study was used as negative control. Precisely, the tissue samples were stained using the same procedure but omitting the primary antibody in order to verify that the immunolabeling was not due to nonspecific labeling by the secondary antibody. In fact, if specific staining occurs in negative control tissues, immunohistochemical results should be considered invalid.
nAChR immunohistochemistry quantification
The degree of positive immunoreactivity in the lungs was defined for every case by two independent and blinded observers as the number of cells with strong unequivocal immunostaining, divided by the total number of consecutive cells counted in the epithelium surrounding both alveoli and bronchioles or divided by the total number of the counted cells in the parenchima, expressed as percentage (nAChR index: nAChR-I). nAChR-I was classified as: "Class 0" for no staining (negativity); "Class 1" when the index was < 10% (weak positivity); "Class 2" with a percentage of immunopositive cells between 10 and 30% (moderate positivity); "Class 3" with an index > 30% of the counted cells (strong positivity).
Comparison among the observations carried out by the two pathologists was performed employing Kappa statistics (Kappa Index- KI) to evaluate inter-observer reproducibility. The Landis and Koch
Markers for fibroblasts and collagen
– Immunostaining procedures for Fibroblast-specific protein-1 (FSP-1; 11 kD) of the S100 superfamily were applied to identify fibroblasts in the lung vessel walls. Skin samples were used as positive controls; negative controls were prepared omitting the primary antibody and replacing only with PBS during incubations. Sections from paraffin-embedded tissue blocks were treated using commercially supplied 1:400 diluted rabbit monoclonal antibodies FSP-1 (Millipore #07-2274). Slides were boiled for the antigen retrieval in 0.01 M citrate buffer (pH 6.0), using a microwave oven, at 600 W for 3 times at 5 min each, and finally cooled. A standard ABC technique avidin-biotin complex (Vectastain elite ABC KIT, PK-6101) was used with HRP-DAB to visualize and develop the antigen-antibody reaction. Sections were counterstained with Mayer's hematoxylin, than coverslipped.
– Heidenhain's trichrome staining (AZAN staining) was applied as histochemical staining procedure to identify the collagen around the airways and the vessels. In this method three acid dyes are used: azocarmine and a mixture of aniline blue and orange G. The azocarmine stain is combined with the mixture of aniline blue and orange G as counterstain, after mordanting with phosphotungstic acid. The collagen and cytoplasmic reticulum appear blue, muscle red to yellow, nuclear chromatine red.
Statistical analysis
Histological and immunohistochemical data were tabulated and analyzed for differences comparing pairs of groups by using the analysis of variance (ANOVA). Statistical calculations were carried out with a SPSS statistical software (version 11.0; SPSS Inc., Chicago, IL, USA). The selected threshold level for statistical significance was p < 0.05.
Lung examination in SIUDS/SIDS
In 38 cases (63%) of sudden death (33 SIUDS and 5 SIDS), a paucity of pulmonary alveoli was highlighted in histological sections demonstrating lower radial counts than the normal reference values (Figure
Figure 1
Histological section of lung parenchima showing the radial alveolar count (RAC) method
Histological section of lung parenchima showing the radial alveolar count (RAC) method. SIDS case, 1 month-old (RAC: 2.5; normal mean value for age: 5.5 ± 1.4). Hematoxylin-eosin stain; magnification: 10×.
nAChR expression
Examination of the immunostained preparations revealed a strong immunoreactivity for the nAChR α7 subunit ("Class 3" of nAChR-I) in densely packed cells of compact lung parenchyma areas (Figure
Figure 2
Positive α7 nAChR expression in a group of cells of lung parenchyma SIUDS case, 38 gestational weeks
Positive α7 nAChR expression in a group of cells of lung parenchyma – SIUDS case, 38 gestational weeks. α7 nAChR immunostain; magnification: 20×.
Figure 3
Positive α7 nAChR epithelial cells surrounding in A) the lumen of an alveolus and in B) the lumen of a bronchiole– SIDS case, 2 month-old. α7 nAChR immunostain; magnification: 40×.
Positive α7 nAChR epithelial cells surrounding in A) the lumen of an alveolus and in B) the lumen of a bronchiole – SIDS case, 2 month-old. α7 nAChR immunostain; magnification: 40×.
Figure 4
Positive α7 nAChR in the wall of pulmonary vessels (see arrows)
Positive α7 nAChR in the wall of pulmonary vessels (see arrows). One of the two vessels shown in A) is represented at higher magnification in B) – SIUDS case, 38 gestational weeks. α7 nAChR immunostain; magnification: A) 10×; B) 40×.
Figure 5
Identification of pulmonary perivascular fibroblasts and collagen
Identification of pulmonary perivascular fibroblasts and collagen. A) identification of fibroblastic cells around a lung vessel by FSP-1 immunohistochemistry (brown reaction product). B) Perivascular blue collagen fibers highlighted by histochemistry – SIDS case, 2 month-old. A) FSP-1 immunostain; magnification: 20x - B) AZAN stain; magnification 20×.
Lung examination in controls
Mostly, in control subjects the RAC was within the normal reference values. Nevertheless, a "low grade of lung hypoplasia" in 2 newborns (8%) who died of pneumonia in the first two months of life, with a slightly lower lung maturation index than the mean value for the age (RAC value: 4; mean reference value: 5.5 ± 1.4).
nAChR expression
A high α7 subunit immunoreactivity ("Class 3" of nAChR-I) was detected in the airway epithelium of 3 newborns, two of whom had died of respiratory infections and showed mild lung hypoplasia.
Correlation of lung observations with maternal smoking
A significant association between a strong expression of α7 nAChR, lung hypoplasia and prenatal cigarette smoke exposure (p < 0.01) occurred. In fact, 20 of the 27 cases with a smoker mother belonged to the SIUDS/SIDS group showing a high α7 immunopositivity and lower RAC values than the reference values. Moreover, the mothers of the 3 control infants with similar nAChR results and mild lung hypoplasia were active smokers in pregnancy.
Brainstem examination in SIUDS/SIDS and controls
The in-depth histological examination, supported by the morphometric analysis, of the brainstem in SIUDS/SIDS cases frequently yielded a diagnosis of hypodevelopment of important nuclei and/or neuronal structures checking vital functions. Hypoplasia/agenesis of one or more nuclei of the raphe system (
In 11 SIUDS with hypoplasia of the obscurus and pallidus raphe nuclei in the medulla oblongata, we observed an association with hypoplasia of the pontine parafacial and Kölliker-Fuse nuclei, consisting of "pre-inspiratory" neurons with the hierarchical function of starting the first breathing movements
Hypoplasia of the medullary pre-Bötzinger nucleus, a critical structure for respiratory rhythmogenesis
In most of these cases (15 SIUDS and 4 SIDS) the mother smoked during pregnancy.
A significant correlation was found between the neuropathological results and the above-reported lung alterations. In fact, in 20 SIUDS and 4 SIDS victims with a defective maturation of important brainstem centers, lung hypoplasia with a high α7 nicotinic receptor expression was discovered.
In controls hypoplasia of the arcuate nucleus was the only finding (observed in 3 cases), not related to maternal smoking. On the whole, SIUDS and SIDS cases displayed a significantly higher incidence of brainstem pathological findings as compared to age-matched controls (p < 0.01).
Further research aimed at evaluating nicotinic receptor expression in the brainstem is now in progress in our laboratory, and will be the subject of a forthcoming publication.
The lung, during its long process of maturation from the embryonic phase of development in utero up to adolescence, is highly susceptible to damage caused by exposure to environmental toxicants, and particularly to tobacco smoke in pregnancy
In pregnant smokers nicotine, that in amniotic fluid reaches similar or higher levels than those present in maternal plasma
Previous experimental studies performed on Rhesus monkeys, an ideal model of pulmonary growth that is very similar to that of humans, demonstrated that nicotine administration during pregnancy causes lung hypodevelopment as a direct result of its interaction with the α7 subunit of the nicotinic receptors, that are widely distributed in the airways epithelium in prenatal life
The involvement of this specific subunit in lung pathophysiology is also proven by its strong manifestation in tobacco-induced cancers. Nicotine contributes directly to pulmonary tumorigenesis through stimulation of the α7 nAChR subunits in target cells, as shown by their overexpression particularly in non-small cell lung carcinomas of patients who smoked
Basing on these results, we propose a potential molecular mechanism responsible for the high incidence of lung hypoplasia in SIUDS and SIDS whose mothers smoked. We hypothesize that the overexpression of the α7 nicotinic receptors we found in these cases is the result of modifications of the corresponding gene expression. This is supported by the increased messenger RNA levels of several nAChR subunits (including α7 subunits) observed in the developing nervous system of rats as a consequence of nicotine absorption
In our study, the α7 nAChR overexpression observed in lung epithelial cells in a high percentage of SIUDS/SIDS victims was exacerbated by the presence of developmental alterations of brainstem centers affecting not only breathing activity but, more in general, all the vital functions, thus amplifying the harmful effect of nicotine and leading to a fatal outcome. The results of the current research now in progress in our laboratory on the α7 nAChR expression in the brainstem, will validate this assertion. It is therefore clear that nicotine, after entering the fetal circulation and crossing the fetal blood–brain barrier, interacts with the α7 subunits and up-regulates its expression in both non-neuronal cells of the lung and in neuronal cells of the brainstem, thereby leading to impaired lung function and hypodevelopment of the respiratory neuronal centers.
The strong immunoexpression of the α7 nAChR subunit also observed in fibroblasts around lung vessels and airways must be underlined. The vascular walls, in particular, appear thicker, very likely due to interactions of nicotine with fibroblast receptors, thereby triggering a high collagen protein synthesis and hence causing accumulation of connective tissue. Nicotine can therefore directly stimulate α 7 nAChR-bearing fibroblasts to lay down an excessive amount of connective tissue.
These considerations are consistent with the report by Sekhon et al.
Collagen deposition around the airways and pulmonary vessels certainly induces an increased airway resistance and decreased respiratory function, providing an explanation for the high incidence of persistent pulmonary hypertension observed in infants whose mothers smoked during pregnancy
It is important to point out several limitations of this study. First, the exact mechanisms by which nicotine interacts with nAChR to alter lung development remain to be determined. This is due, in particular, to the impossibility to perform experimental studies in humans. However, based on our results we can hypothesize a link between α7 overexpression and delayed pulmonary development in SIUDS/SIDS victims. Secondly, pertaining to cigarette smoke exposure, is that available information on our cases did not provide evidence of an exposure 'dose'. Furthermore, it should be considered that retrospective assessment of the maternal smoking, particularly if performed after a fatal event, is sometimes unreliable, due to the fact that mothers who smoke are reluctant to admit tobacco use, because of feelings of guilt
This article emphasizes the extreme vulnerability of the developing lung to maternal cigarette smoke absorption. In summary, we claim that nicotine in pregnant women is readily transported across the placenta, achieving sufficient levels to interact directly with the nicotinic receptors that are widely distributed in the lung cells in prenatal life. In particular, on the basis of our results and of previous experimental studies, we propose α7 nAChR as the main candidate mediating the pathobiologic effects of tobacco products on lung maturation and function. The specific interaction of nicotine molecules with α7 subunits, widespread in the cytoplasmic membrane of both lung epithelial cells and fibroblasts, leads to an overexpression of the corresponding receptors with a consequent severe inhibition of airway development
Despite the compelling evidence that prenatal nicotine absorption increases the incidence of pulmonary diseases in fetal and infant life, in addition to posing the well known risks of spontaneous abortion, preterm delivery, low birth weight and sudden perinatal death, a significant number of women continue to smoke during pregnancy.
The findings of this study further underline the importance of ensuring widespread information about the noxious potential of nicotine absorption in pregnancy, as well as the need to implement measures to prevent this major and avoidable cause of lung morbidity and mortality in fetuses and infants.
aThis law decrees that all infants suspected of SIDS, suddenly died in Italian regions within the first year of age, as well as all fetuses who died without any apparent cause (SIUDS), must undergo an in-depth anatomo-pathological examination, particularly of the autonomic nervous system.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
AML planned the study, analyzed the data and wrote the manuscript with collaborative input and extensive discussion with LM. MFC and GA carried out the immunohistochemical and the histochemical study and participated in the evaluation of the results. All authors read and approved the final manuscript.
The authors thank Ms. Mary Victoria Candace Pragnell, B.A. for English revision of this manuscript.
This study was supported by the Italian Health's Ministry in accordance with the Law 31/2006 "
Smoking during pregnancy, 1990–1996
Change in observed birth weight associated with change in maternal cigarette smoking
Prenatal smoking and risk of intrapartum stillbirth
The effects of maternal smoking on fetal and infant mortality
Maternal smoking during pregnancy and lower respiratory tract illness in early life
Maternal smoking habits and cognitive development of children at age 4 years in a population-based birth cohort
Extent of nicotine and cotinine transfer to the human fetus, placenta and amniotic fluid of smoking mothers
Nicotinic acetylcholine receptors in health and disease
The molecular biology of neuronal nicotinic acetylcholine receptors
Mammalian nicotinic acetylcholine receptors: from structure to function
Subtypes of nicotinic acetylcholine receptors in nicotine reward, dependence, and withdrawal: evidence from genetically modified mice
Neuronal nicotinic receptors: from protein structure to function
Structural and functional diversity of native brain neuronal nicotinic receptors
The dynamic effects of nicotine on the developing brain
Immunohistochemical localisation of nicotinic acetylcholine receptor subunits in human cerebellum
Acetylcholine beyond neurons: the Non-neuronal cholinergic system in humans
Neuronal nicotinic acetylcholine receptors: not just in brain
Nicotine activates and up-regulates nicotinic acetylcholine receptors in bronchial epithelial cells
Prenatal nicotine increases pulmonary alpha7 nicotinic receptor expression and alters fetal lung development in monkeys
Prenatal nicotine exposure alters pulmonary function in newborn rhesus monkeys
Association between pulmonary hypoplasia and hypoplasia of arcuate nucleus in stillbirth
Infant and perinatal pulmonary hypoplasia frequently associated with brainstem hypodevelopment
Techniques and criteria in pathologic and forensic-medical diagnostics of sudden unexpected infant and perinatal death
Guidelines for neuropathologic diagnostics of perinatal unexpected loss and sudden infant death syndrome (SIDS): a technical protocol
The number of alveoli in the terminal respiratory unit of man during late intrauterine life and childhood
The measurement of observer agreement for categorical data
The human raphe nuclei and the serotonergic system
Hypoplasia of the parafacial/facial complex: a very frequent finding in sudden unexplained fetal death
Hypoplasia of the Parabrachial/Kölliker-Fuse complex in perinatal death
Functional neuroanatomy of the human pre-Bötzinger complex with particular reference to sudden unexplained perinatal and infant death
Hypoplasia of medullary arcuate nucleus in unexpected late fetal death (stillborn infants): a pathologic study
Environmental factors and developmental outcomes in the lung
Fetal and postnatal development of the lung
Chronic maternal nicotine exposure during gestation and lactation and the development of the lung parenchyma in the offspring. Response to nicotine withdrawal
Prenatal development of lung antioxidant enzymes in four species
Physiologic effects of maternal smoking on breast-feeding infants
Prenatal nicotine exposure alters lung function and airway geometry through α7 nicotinic receptors
Interaction of tobacco-specific toxicants with the neuronal α7 nicotinic acetylcholine receptor and its associated mitogenic signal transduction pathway: potential role in lung carcinogenesis and pediatric lung disorders
Role of alpha7-nicotinic acetylcholine receptor in human non-small cell lung cancer proliferation
Exposure to prenatal nicotine transiently increases neuronal nicotinic receptor subunit α7, α4 and β2 messenger RNASs in the postnatal rat brain
Expression of the alpha7 nicotinic acetylcholine receptor in human lung cells
Prenatal nicotine exposure increases connective tissue expression in foetal monkey pulmonary vessels
Maternal tobacco smoke exposure and persistent pulmonary hypertension of the newborn
Accuracy of mothers' retrospective reports of smoking during pregnancy: comparison with twin sister informant rating
Pre-publication history
The pre-publication history for this paper can be accessed here:


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Hey trillian, veretas, fightinfilipino - are we still roomingh?
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he life of Austrian writer Stefan Zweig in Brazil. He wrote the famous book "Brasil, País do Futuro" (Brazil, Country of the Future). He and his wife Lotte, in a mysterious death pact, decided to kill themselves in the week following 1942 Carnival, in Brazil.Resumen IMDb.com
|Nombre del documento
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text: Even the OCC wrote in its most recent report, "The decline in new foreclosures and foreclosures in process reflects a strengthening economy, a declining number of serious delinquencies, and an emphasis on alternatives to foreclosures." So, why spend probably another half a billion dollars to extend a program that has not lived up to its expectations? One that has only proven the longer a homeowner is involved in HAMP, the more likely they are to redefault. Even those that receive a permanent modification are getting cancelled at a rate of 14%. One reason was to align HAMP's deadline with other extended deadlines for other programs like the Home Affordable Refinance Program (HARP), a refinancing program administered by the Federal Housing Administration (FHA). This makes perfect sense. Spend an additional half a billion dollars so a deadline will align with a separate program from a different department. The HARP program isn't even reflected in the SIG TARP report on TARP expenditures anymore. At one time HARP was reviewed along with the Making Homes Affordable program, but not anymore. The Special Inspector General is also worried that an extension of the program could lead to more fraud. Ultimately, the extension is about saving face. The Treasury is going to spend $18 million in an outreach program to try to convince more homeowners to ask for assistance. The money goes to non-profit groups that will receive $5,000 to kick off the program and $450 for each application, whether it results in a modification or not. This program began on May 1, and the HAMP extension went through on May 30. Excellent timing. If a homeowner hasn't requested help over the last five years, does it really make sense to spend $18 million to go out and find them? Beg them to apply for help? Pay groups to find them? Only if it will result in the ability of the Treasury to be able to say it helped more people. When the Treasury is pressed for an answer, a spokeswoman could only repeatedly say they wanted to help more people. Really the Treasury only wants to tout the number of people it has reached out to to help, not the number of people that can get approved and can actually stick with the program.


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How do I get rid of wrinkles under my eyes at the age of 20 years old? (photos)
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How do I get rid of wrinkles under my eyes at the age of 20 years old?
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I would start of Retin A and a good eye cream with growth factors. I don't think that fillers or Botox is needed at this time. Perhaps PRP would be of benefit. Microneedling can be done as well.
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The effect of male sodium diet and mating history on female reproduction in the puddling squinting bush brown Bicyclus anynana (Lepidoptera)
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The males of butterflies transfer a spermatophore to the female during mating that can contain nutrients enhancing the reproductive potential of their partners. The nutrients transferred by males can be derived from both larval and adult feeding. These nutrients may be depleted by multiple matings. An apparent difference in adult feeding behaviour between the sexes is puddling on mud, dung and carrion, which in most butterfly species is exclusively a male behaviour. A possible explanation for this division in feeding behaviour is that nutrients derived from puddling by males are transferred to the female during mating. Here, we test this hypothesis in the African fruit-feeding butterfly Bicyclus anynana. We varied the male nuptial gift by (1) feeding males either a diet with or without sodium, and (2) varying the number of previous successful copulations by remating males up to five times on consecutive days. The results show both a strong effect of order of mating on the mating duration, and an individual effect with some males typically copulating for a shorter time than others. The effects on female reproduction were, however, minimal. The total number of eggs per female and the sodium content of the eggs did not differ significantly between diets, nor were they affected by the mating histories of the males. Eggs showed a non-significant lower hatching for females partnered by a male who had already mated several times. There was an indication of an interaction with male diet: the sodium treatment showing a decline in egg hatchability with order number of male mating, whilst the control treatment showed a constant hatchability. The results are discussed in relation to determinants of male gift-giving strategy and to other potential explanations for a restriction of puddling to males in butterflies.


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We provide a full range of Bespoke Software Development and Technical Consultancy Services for healthcare organisations, and we work to HL7, ICD-10, and DMD technical healthcare standards.
If you require a customisable 'off-the-shelf' product or solution to improve Patient Flow Management in your hospital or healthcare organisation, we're the right people to talk to - just take a look at our Products page for our full range.
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As a division of Blueberry Consultants, Blueberry Health has access to specialists with extremely strong technical skills and practical experience in software development across a wide range of industries - from healthcare to aerospace - allowing us to find innovative solutions that another consultancy may not have considered.
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Our core Software Development Services include:
Design and development of standalone Windows ApplicationsBlueberry is an expert developer of standalone and client-server applications for the Microsoft Windows platform. As a company, Blueberry has been developing software for Windows for over 10 years, and has worked on every major version of Windows from Windows 3.1 to Windows 7.
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Database Applications & Systems Blueberry Health designs and implements database applications & systems using Microsoft SQL Server, MySQL or Oracle. Any organisation that relies on information to streamline workflow and optimise efficiency will require a database system that is accessible to the right people throughout the organisation. Blueberry Health can create a custom application to deliver the information you need directly to a PC, or we can create a Web-based application, so that the information is delivered via a Web Browser, accessible to only the users permitted access.
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Do you need help with an internal development project that is behind schedule, or isn't delivering what you need? We can provide impartial advice on what needs to be done – as we did for a major NHS research organisation earlier this year. We also have plenty of experience of picking up existing projects and turning them round – no matter what state they're in.
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"Blueberry has a track record, built over ten years, of delivering high-quality software systems that deliver real results."
Martin Green, MD, Blueberry Health
(c) Blueberry Consultants Ltd 2010-2014.


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A bill extending and reforming U.S. agricultural programs cleared a key legislative hurdle Thursday as the Senate approved a five-year, half-trillion-dollar farm bill by a vote of 64 to 35.
The Senate appeared to cast aside partisan politics to pass bill, which will help low-income Americans buy food and compensate U.S. farmers for crop losses.
"The Agriculture Reform Bill is about standing up for our nation's farmers, our small businesses, our manufacturers, our exporters and others, whose livelihood depends on us getting the policy right," said Sen. Debbie Stabenow, a Michigan Democrat and chairwoman of the Senate Committee on Agriculture, Nutrition and Forestry, who spoke moments before the vote. "This represents significant reform. It cuts subsidies. It cuts the deficit. It creates jobs."
The bill, which seeks to trim costs from an $80 billion-a-year program that helps 46 million poor Americans buy food, also replaces a subsidy program that pays some farmers — regardless of whether they plant crops — with a new initiative designed to assist farmers who suffer losses on crops actually planted.
U.S. farm subsidies have been a persistent irritant to many other agriculture-exporting nations, such as Brazil, that argue the payments are an unfair trade barrier and harm developing economies.


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UK Tax
UK Tax Questions? Ask a UK Tax Advisor for answers ASAP
Hi Tony, thanks for the prompt response
Yes, she was renting out a UK property when she was studying aborad. I think she thought she would be able to claim back some employment tax (NI?) although I'm not sure this was based on expert advice.
Thanks Tony - just to be clear, the main question is whether she will be able to appeal against the fines (which are up to over £2,500 now) on account of not having received the returns as they were sent to an address where she no longer lived.
Thanks for the thorough and prompt reply Tony - this is very useful.


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Te-vijja: 'one endowed with the threefold higher knowledge'. In Brahmanism means 'knower of the 3 Vedas' tri-vidyā in Buddhism means one who has realised 3 kinds of knowledge, to wit: remembrance of former rebirths, the divine eye, ceasing of all fermentations.
Maha Thera Nyanatiloka. Manual of Buddhist Terms and Doctrines, Buddhist Publication Society, first edition 1952.


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Follow your favorite team, check the latest score or participate in the community. We have thousands of Sports Apps for Android Phones and Tablets.
Click on the title of this section to expand the list and show you every app in our system!
[download_page pop_count="14″ per_page="5″ exclude_cat="430″]
27 Comments
Can someone find an Edmonton Oilers app for android?
when i try to convert to a bar file it says it's unconvertable and that the version number is too long
Gamechanger app won't download. Help
Nice App.
very nice app works for me
Any idea how to convert this app to a .bar? Getting an error that says it's unconvertable and that the version number is too long
Nice one!!! Thanks for update.
May I ask if someone with convert this to a .BAR file for Blackberry 10?
Can you please convert this to a BB10 app…
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Diamond Creek Red Rock Terrace Cabernet Sauvignon 2010, Diamond Mountain District, Napa Valley
Cabernet Sauvignon
California, Usa
$300.00 (Agent)
95 pts
Critic Reviews (2)
Julian Hitner
Tasted alongside the Volcanic Hill and Gravelly Meadow (which is what I almost always end up doing), the 2010 Red...Sign In to see Critic Reviews. Not a Member? Please Sign Up.
John Szabo, MS
The Red Rock Terrace is aromatically closed at the moment, yet the palate, at least initially, has a lightness and a...Sign In to see Critic Reviews. Not a Member? Please Sign Up.


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Agriculture is a key industry for the future of Colorado. We will work to create new business opportunities for Colorado's farmers and ranchers, spur innovation and make our rural communities a great place to live and prosper. Strong rural communities, with schools, hospitals, restaurants, and businesses help create a sustainable long-term local economy that can attract a younger generation to continue the proud tradition of farming and ranching in Colorado.
Key Priorities
* Take advantage of new renewable energy opportunities.
* Water: Protect rights, quality, and ensure capacity.
* Make sure Colorado's needs are reflected in the 2012 Farm Bill.
* Support Agriculture Conservation Easements.
* Stop losing agricultural land: Pinon Canyon
"A strong Colorado economy depends on a prosperous rural Colorado. We are committed to ensuring that Colorado's rural communities are vibrant and thriving economically, and recognize the unprecedented opportunities at hand to support this revitalization."
-John Hickenlooper
Agriculture in Colorado is about more than just crops and livestock. Agriculture is also a way of life, a significant engine for individual entrepreneurship and a foundation for our economy in the West. Agriculture is interdependent on the other key variables that make for a healthy community: education, health care and economic development. Thriving rural communities and sustainable agricultural policies contribute significantly to the health and well-being of everyone in Colorado. Farmers and ranchers in Colorado are the producers of our food and fiber; they are the original conservationists of our land and resources, and part of the fabric of our state. As a core element of our economic development strategy we must focus our efforts to promote Colorado products.
While the agriculture industry has endured some turbulence from fluctuating dairy and agriculture prices, to record high input costs for all producers over the last half decade, Colorado's farmers and ranchers, through their innovative strategies and commitment to proven science-based solutions, have continued to produce efficiently and profitably. Undoubtedly, there are challenges. We must address the competing interests for land and especially for water. Most importantly, we realize that providing long-term fiscal stability to our agriculture community is critical to the success of these industries, and will enable our farmers, ranchers, and rural communities to prosper and grow.
Strategies and Solutions
Creating New Opportunities for Prosperity: We must support Colorado farmers and ranchers to be competitive and capitalize on new income opportunities in local, national and global markets. This is possible by connecting producers with consumers in both domestic and foreign markets. A thriving agricultural community will have a direct relationship to growth and expansion of our rural communities. A robust agricultural community helps create more than food and resources, it helps to support schools, hospitals, restaurants, and businesses, all of which significantly improve the quality-of-life for our rural and urban communities.
We will work to increase agricultural exports and invest in research and development to strengthen farm income and profitability. In part, we will achieve this by utilizing higher education assets such as Colorado State University (CSU), one of the premier research and land grant universities in the nation. As the economy develops, we will work to advance education opportunities to our rural communities, in order to help equip tomorrow's farmers and ranchers with the best research, science-based solutions, and business support for their enterprises.
We will pursue all avenues of research and development within Colorado's higher education system, the federal Department of Agriculture and other institutions to make Colorado a recognized leader in agriculture research. Such an example is drought resistant crops, which could pave the way for the future of agriculture in Colorado. As technology continues to advance, we must also invest in broadband access and availability to connect all parts of our communities. We will work to identify public-private partnerships and federal grants to integrate access.
Renewable Energy: We will work with Colorado's industries, energy businesses, and private landowners in order to lay the foundation for the infrastructure needed to transmit renewable and sustainable energy sources like wind and solar to support a stronger rural economy. See Energy Policy.
Protecting and Conserving Colorado Water: We recognize the need for a collaborative approach on water issues, since protection for water rights, quality, quantity, and capacity are all critical to the economic success of Colorado. Fortunately, farmers and ranchers know better than most, that cooperation is essential when it comes to protecting our water resources. Just as our renewable energy such as solar and wind need a modernized electrical grid to effectively transmit power across the country, our farmers, ranchers, and local communities need reliable storage and efficient water delivery systems. See Water Policy.
Conservation & Job Creation in Rural Communities: A 2008 report from the Trust for Public Land in Colorado concluded that for every $1 invested into conservation programs, the State received $6 in benefits. See Conservation Policy.
The USDA recently announced $6.7 million in grant and loan funding rewarded to farms in Colorado to promote job creation. This federal funding could potentially create hundreds of full-time jobs. We will work closely with our industries and businesses to leverage and maximize the impact of these federal funds, in order to advance our economic recovery in Colorado. Colorado is poised to take advantage of these opportunities and we should make every effort to do so.
The 2008 Farm Bill: This legislation provides a safety-net for agriculture producers through traditional commodity programs, funding for specialty crops, and programs to advance bio-fuel and renewable energy research and development. We know that Congress has begun to discuss the next Farm Bill, which is scheduled to be renewed in 2012. While budget constraints will dictate much of the framework, we must ensure that our most successful provisions remain, and think creatively about how to shape new provisions that will provide additional support and opportunity for our producers in Colorado. We will work to maximize the farm safety net and incentives to obtain the maximum benefit for Colorado's agricultural producers as negotiations begin on the 2012 Farm Bill.
Agriculture Conservation Easements: More than 1.8 million acres of Colorado farms were converted to other uses in the past decade, placing Colorado third in the nation for the amount of agriculture land lost. We must preserve our agriculture land for future generations. We will work closely with conservation organizations to help Colorado's ranchers and farmers protect their land, encourage ongoing agriculture production and recognize the importance of prohibiting or severely limiting any practice such as subdivision or development that would damage the land's agricultural or conservation value and productivity. We will also encourage industries to become working partners and a valuable resource that can help significantly by contributing private funds towards conservation easements. This will support farmers to keep their land within the family, and conserve land for future generations.
Benefits of conservation easements include:
* Protecting private property rights to ensure that future generations have the opportunity to remain in the agriculture production industry.
* Significant financial benefits through the reduction of federal income taxes, gift taxes, and estate taxes as well as state income tax credits.
* Support robust fish and wildlife populations, reduce watershed, and help curb the effects of pollution.
While the projected benefits of conservation easements are of good intention, we are cognizant of the need for an independent, third party to verify and oversee the easement process, to ensure that our ranchers and farmers are compensated with a fair market value, and that the land is properly conserved.
Economic Impacts of Land Conservation: Farms and ranches also support a robust outdoor recreation economy, generating tourists from around the globe and supporting thousands of jobs throughout the State. There are more that 593,000 resident hunters and anglers in Colorado that generate $1.2 billion in direct spending annually. This creates an additional $2.1 billion ripple effect on the Colorado economy for a total economic impact of $3.6 billion within the State.
Active outdoor recreation in Colorado also provides significant economic benefits, supporting 107,000 jobs, generating nearly $500 million in annual state tax revenues, and producing $7.6 billion in retail sales and services across Colorado. Colorado is a national leader in land conservation and park creation thanks to the combination of funds from local, state and federal programs. These efforts should be continued and supported by Colorado's next Governor.
Protecting Colorado's Ranchers: A Position on Pinon Canyon: As most ranchers and livestock operators in Colorado know, there is a great deal of concern about the Army's plans to expand the boundaries of Fort Carson's training facilities at Pinon Canyon in southern Colorado. It is not enough to oppose the use of eminent domain (condemnation) at Pinon Canyon. In an already fragile economy, it is not fair to add more pressure to landowners in the area. That is why we support the state legislative ban on the lease or transfer of state lands for expansion, why we support the Congressional moratorium on expansion activities and why we are opposed to the additional loss of productive land in agriculture and livestock production that would follow from Army expansion. It is important for the communities most impacted by the Army's planned expansion in Southern Colorado to have the ultimate say in whether they would agree to any expansion proposal. It has been clear to us that so far, communities in Southern Colorado are adamantly opposed to the loss of this land (even through leasing) and we believe Colorado's next Governor must stand with them.
Source: http://www.hickenlooperforcolorado.com/issues?id=0008


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Safety Study on IdeS in Healthy Volounteers
This study has been completed.
Hansa Medical AB
Information provided by (Responsible Party):
Hansa Medical AB
ClinicalTrials.gov Identifier:
First received: February 27, 2013
Last updated: January 18, 2017
Last verified: January 2017
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Detailed Description:
This is a first in man study to assess safety and tolerability of the IgG cleaving enzyme Immunoglobuli G degrading enzyme of streptococcus pyogenes (IdeS).
|Drug: IdeS Drug: Placebo
|Phase 1
|Study Type:
|Study Design:
|Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double Blind (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
|Official Title:
|A Phase i Single Center Study to Evalute the Safety, Tolerability and Pharmacokinetics of Intravenous IdeS After Administration of Single Ascending Doses in Healthy Male Subjects
Further study details as provided by Hansa Medical AB:
Primary Outcome Measures:
- Safety as measured by adverse events [ Time Frame: 64 days ]
Secondary Outcome Measures:
- Peak plasma concentration of IdeS [ Time Frame: 7 days ]
Other Outcome Measures:
- Total IgG concentration [ Time Frame: 64 days ]
|Study Start Date:
|February 2013
|Study Completion Date:
|February 2014
|Primary Completion Date:
|December 2013 (Final data collection date for primary outcome measure)
|Assigned Interventions
Experimental: IdeS
Intravenous infusion
|Drug: IdeS
Placebo Comparator: PBS Buffer
Intravenous infusion
|Drug: Placebo
Detailed Description:
A phase I study (11-HMedIdeS-01, EudraCT no. 2012-000 969-21) first in man single ascending dose study in 29 healthy subjects to investigate if IdeS is safe and well tolerated in doses up to 0.24 mg/kg body weight (BW).
|Ages Eligible for Study:
|18 Years to 45 Years (Adult)
|Sexes Eligible for Study:
|Accepts Healthy Volunteers:
Inclusion Criteria:
- Ability to understand and sign informed consent
Exclusion Criteria:
- Clinically significant disease
Positive HIV, hepatistis B or C
- Drug abuse
- Smoking
- Use of medication except paracetamol
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01802697
Please refer to this study by its ClinicalTrials.gov identifier: NCT01802697
|Clinical Trial Unit, FoU centrum Skåne, Skåne University hospital
|Lund, Sweden, 22185
Sponsors and Collaborators
Hansa Medical AB
|Principal Investigator:
|Ulf Malmqvist, MD, PhD
|Clinical Trial Unit, SUS, Lund, Sweden
More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Keywords provided by Hansa Medical AB:
ClinicalTrials.gov processed this record on July 19, 2017
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Winstedt L, Järnum S, Nordahl EA, Olsson A, Runström A, Bockermann R, Karlsson C, Malmström J, Palmgren GS, Malmqvist U, Björck L, Kjellman C. Complete Removal of Extracellular IgG Antibodies in a Randomized Dose-Escalation Phase I Study with the Bacterial Enzyme IdeS--A Novel Therapeutic Opportunity. PLoS One. 2015 Jul 15;10(7):e0132011. doi: 10.1371/journal.pone.0132011. eCollection 2015.
|Responsible Party:
|Hansa Medical AB
|ClinicalTrials.gov Identifier:
|NCT01802697 History of Changes
|Other Study ID Numbers:
2012-000969-21 ( EudraCT Number )
|Study First Received:
|February 27, 2013
|Last Updated:
|January 18, 2017
|Individual Participant Data (IPD) Sharing Statement:
|Plan to Share IPD:
Keywords provided by Hansa Medical AB:
ClinicalTrials.gov processed this record on July 19, 2017


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|Message view
|« Date » · « Thread »
|« Date » · « Thread »
|Erik Daughtrey <er...@schemacity.org>
|Re: Does there need to be a default web container?
|Fri, 09 Dec 2005 00:26:07 GMT
I may have phrased the original issue badly. The installer has both Jetty and Tomcat as options to install on the main pack selection page. It was decided that because of the complexity of installing two web containers that we should not install both, but allow the operator to select one or the other. In M5, the installer actually allowed both containers to be configured, but did not have a way to validate the ports selected. When configured correctly with no conflicting ports, both containers will start. There's some goofiness with offlineDeployer and runtimeDeployer since one of the containers will win the config.xml entries if more than one is selected -- looks like Tomcat wins. For 1.0, both containers will be listed on the first selection screen. However, it didn't make sense to default both to install when the plan was to only allow one. Allowing both requires the installer to validate the ports and ensure that the operator does not configure both containers to the same port. This problem exists for other port types as well, but is less likely to be a problem. IzPack does not support this inter-panel validation easily i.e. through normal XML based configuration. It requires that java code be built to extend the user input panels. On the other hand, limiting the operator to one web container is no panacea either. To effectively do this, I have configured the XML to set Jetty as the default to install (Tomcat can be selected) since it's confusing to do otherwise in this scenario (although the default could just as easily be Tomcat and it looks like the vote is going that way). This effectively starts down a good path for this scenario, but the operator can easily select both containers again. To stop this, I will extend a userinput panel to be invoked to check that both are selected and not allow the install to proceed past the first userinput screen -- the first screen after the major component selection. This again requires java code since IzPack does not have a parameter to apply to packs such as "exclusiveOf( packName )". This is interesting since it does have "depends( packname )" which allows us to require the Tomcat container when installing the Tomcat console, etc. This may be more than everyone wants to know, but to answer your question, I don't see any particular reason why the installer cannot allow installation of both. However, it's very late in the 1.0 cycle and the current design is that we'd allow one or the other, but not both. I have no particular preference myself. On Thursday 08 December 2005 18:30, Jeff Genender wrote: > This is obviously a hot topic and I hope that as a Geronimo PMC and user > community we are not forced to have to show preference of one over the > other. There is obviously some personal preferences on both sides and > we are a great open source project because we do not have to get behind > one *or* the other. We can get behind them both. > > May I ask why the installer/wizard cannot have a page called "Choose > Your Web Container" and have an option for Jetty and Tomcat, but neither > selected? Does there need to be a default? Can we just let the end > user choose? > > IMHO, I don't think we should provide a preference for one over the > other. I really like both. I think we should give the user the choice > without hinting a preference. > > Thoughts and comments? > > Jeff -- Regards, Erik
|View raw message


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Key Points You Need to Remember When Selecting a Research Peptides Supplier
Research peptides are increasingly popular for all those who like to experiment in their labs at home. Easily available online from a number of reputable suppliers, peptides can often be available for excellent prices and can be shipped the world over. However, due to their restricted legality in some countries it is always important to check before you buy.
The first key point that you need to remember when you are selecting a supplier for your research chemicals is that they are operating within the law in their respective country. You also need to make sure that they ship to your country, whether you are buying CJC-1295 without-DAC, ACE-031 or MGF peptide for your experiment.
The most reputable suppliers will state that they only sell their peptides for research purposes, and that products should not be used outside their intended purpose, which is Vitro research in the home or professional laboratory; this information can often be found on the company's web page.
Next, you need to make sure that the supplier sources their research peptides from the best laboratories. This is important as purity and quality is absolutely essential for a number of experiments, especially if you buy CJC-1295 without-DAC or something else for the purpose of testing its reaction to a number of other cells.
Any impurities can compromise the validity of the results of your experiment in the laboratory, so proof that the supplier that you are buying from offers only highest quality materials is very important. Normally the most reputable suppliers will offer a certificate of purity and results of their own lab testing to put your mind at ease.
The third thing you need to check for with any supplier is that all the items that you are buying are stored correctly and packaged safely in order to avoid compromising their quality. Many research peptides are necessary to be stored at freezing temperature in order to retain their integrity over a longer period of time.
Check with the supplier about their storage methods in order to be reassured that you are getting quality in that items have not been compromised by fluctuations in temperature or other external conditions. This is also true during the transportation of the goods.
A fourth and final key point that you need to bear in mind when selecting a supplier if you want to buy CJC-1295 without-DAC, LGD-4033 or another peptide, is that you should have the opportunity to return or replace the items if they are not up to scratch.
One of the major risks of buying online or having goods shipped from another country is that often it can be difficult to return a product that you are dissatisfied with.
When you are investing in quality peptides, make sure that the company is reputable enough to accept returns that are damaged or incorrect, and verify the return and refund process early on in order to avoid disappointment and a waste of your money.
By keeping all these tips in mind, you can invest in your research peptides for use in your home laboratory without hassle. All of these are signs of a reputable retailer, so make sure that they fulfil all these aspects before you click the buy button.


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Posted on August 05, 2014
Brand: Sabian
With the Sabian Grip Disc Practice Pad, practicing your paradiddles just got a whole lot easier. The Grip Disc from SABIAN Performance Accessories allows you to practice anywhere, any time, on almost any surface. The secret is the Grip Disc's sticky back technology, which allows you to place the Grip Disc on a surface, play, and lift up again without leaving any unsightly marks. If the Grip Disc gets dirty...no sweat. It can be easily washed off and is ready again to stick and play. At 6" diameter, the Grip Disc is easily transportable. Just put it in your stick bag and GO!
No reviews available.
Posted on August 05, 2014
Posted on July 05, 2014
Posted on April 14, 2013


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posted by deana .
using this information: if an object is thrown straight up into the air from the height H feet per second then at time tseconds the height of the object is
-16.1t^2 +Vt+ H feet.
This formula uses only gravitational force, ignoring air friction. It is valid only until the object hits the ground or some other object.
Find a function b such that b(v) is the length of time in seconds that a ball takes to reach its maximum height when thrown straight up with initial velocity V feet per second


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Leftovers: Gaming
Unvanquished Free First-Person Shooter Game Gets Its First Release for 2016
The guys over Unvanquished, a free and open-source FPS (First-person shooter) game for GNU/Linux, Mac OS X and Microsoft Windows operating systems have just returned from their Winter holidays and released the first Alpha build for 2016.
SDL 2.0.4 Was Quietly Released Last Week With Wayland & Mir By Default
SDL 2.0.4 is the release that most notably enables Mir and Wayland support by default! It was just by chance I stumbled across the new release earlier today and doesn't seem to really be advertised. SDL 2.0.4 was long overdue and besides enabling the Mir and Wayland back-end support by default it also adds IBus IME support, support for EmScripten and Google Native Client, modern CPU feature detection, Vivante video driver support, and much more.
Slime Rancher pre-alpha, DRM free, available for Linux
Slime Rancher is the tale of Beatrix LeBeau, a plucky, young rancher who sets out for a life a thousand light years away from Earth on the 'Far, Far Range' where she tries her hand at making a living wrangling slimes. With a can-do attitude, plenty of grit, and her trusty vacpack, Beatrix attempts to stake a claim, amass a fortune, and avoid the continual peril that looms from the rolling, jiggling avalanche of slimes around every corner.
SteamOS beta updated to support Xbox One Elite gamepad
For those not keeping an eye on the latest SteamOS updates, a new beta was pushed out a few days ago! It's good to see Valve keeping up with new hardware support.
The Wine Development Release 1.9.1 Is Now Available
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I have a Windows 7 x64 PC running Spiceworks which I'm trying to scan two Windows 7 x64 laptops with. All are members of the same homegroup and the same workgroup.
Spiceworks fails to scan both laptops even with the firewall turned off with 'check account, password or WMI configuration'.
I have found several similar-ish posts but some have domain members and others have different results from the wmic command.
Mine fails from the Spiceworks server to both machines using: wmic /user:username /password:yourpassword /node:remotemachine systemenclosure get serialnumber
with the error 'access is denied'.
Any ideas? This seems to be a common problem through all the versions of Spiceworks I have used and on some machines I have never managed to get it working.
This topic was created during version 5.3.
The latest version is 7.5.00101.
7 Replies
May 11, 2012 at 4:27 UTC
I had to change two settings in Win7 Windows Firewall Advanced Settings. Under Inbound Rules, find Windows Management Instrumentation (WMI-IN) and set allow for Domain and Private, Public. This fixed the two machines I was having a time with.
May 11, 2012 at 4:27 UTC
Did you try WMI Diagnosis Utility? VB-script generates verbose log with recommendations.
May 11, 2012 at 4:32 UTC
the account with spiceworks scan the laptops are setting to access WMI ?
May 11, 2012 at 4:32 UTC
@Rormeister - I have turned the firwall off completely - no change.
@Vasily - I'll give that a try, thanks.
May 11, 2012 at 4:47 UTC
Piers, out of curiosity, what are the settings for WMI-In on those devices. I'm not 100% convinced that having the firewall turned "off" indeed ignores every setting.
May 31, 2012 at 3:52 UTC
The reg change in this post fixed it for me - nothing else worked.
This discussion has been inactive for over a year.
You may get a better answer to your question by starting a new discussion.


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Forbes has released its 2011 list of the Forbes Fab 40.
The magazine has rankings in four categories: athletes, businesses, events and teams.
Teams: Using a data base the they invented, Forbes ranks the New York Yankees at the top. Manchester United and the New England Patriots followed them on the list.
Sporting Event Brand: The Super Bowl was voted at the top for the third consecutive year with The Olympics (Winter and Summer combined) gaining thanks to broadcasting and digital rights.
Most Valuable Athlete Brand: Tiger Woods remains at No. 1 despite his problems with health and not winning in two years. LeBron James is No. 2.
Business Brand: Nike is at the top followed by ESPN.
Reid Cherner has been with USA TODAY since 1982 and written Game On! since March 2008.
He has covered everything from high schools to horse racing to the college and the pros. The only thing he likes more than his own voice is the sound of readers telling him when he's right and wrong.
Michael Hiestand has covered sports media and marketing for USA TODAY, tackling the sports biz ranging from what's behind mega-events such as the Olympics and Super Bowl to the sometimes-hidden numbers behind the sports world's bottom line.


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We stayed here for a quick getaway the weekend after July 4th. The hotel staff here is super friendly and the hotel seems very clean. The hotel rooms are pretty up to date and in good condition. We enjoyed using the indoor pool with our daughter in the evening. It seemed clean and well stocked with towels. Our only complaint was that the beds were not as comfortable as we would have liked, so we didn't sleep that well. Lots of kids around, but they didn't seem to make noise in the halls or be disorderly. The hotel is a little far from the beach and boardwalk, so be prepared to head out early if you visit during the peak season. We plan on returning next summer.
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we stayed for one night to catch our early flight in Narita airport. it was around 11 am when we arrived. the staff let us store the luggage first. we came back after 3 pm and luggage were already in room. there were kitchenette and...More
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"the rate on this hotel can range by over 50% on days and weekends, which is why I booked two 3-days stays..."


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We All Fall Down
Word count: 1358.
Disclaimer: If I owned it, it would have been canon.
The quote at the end contains possible spoilers for season six.
All it takes is a sentence. A single one. That's all; nothing more, nothing less. All the space creatures, the time villains, the annoying baddies who do not know when to give up; they all seem so little when compared to a single sentence. One sentence; four little words. That is all it takes to turn his entire existence upside-down and all wibbly-wobbly. It's almost funny, he supposes, in some sort of twisted way.
"I'm worried about Amy."
And so it begins. Or finishes; depends on how you look at it, really.
Rory tells him everything, every concern, every last fear. He's afraid Amy is falling too deep into their travels, that she is losing herself. He says more than that, though. Of course he does; Rory always has more to say to him.
Not that it matters. No, not in the slightest, because he already knows. Of course he does; you do not get to be as old, as wise, as experienced as him without realising these things on your own. The more time she spends on the TARDIS, the more time she spends with him, the further she separates herself from Leadworth. And the further she separates herself, the harder it will be to go back. He doesn't want her to go, but he knows that if she doesn't go now, she will not ever be able to. And he will not do that to her; won't take away the little chance of normalcy she has left. Won't do it; can't do it.
Not that she will ever go back if she knows what they're thinking. No, no, that would be far too simple, far too easy. Amy is more complicated than that; she is too bloody stubborn for that. In fact, it would only serve to encourage her. Because if there is one thing he has learnt about his mad, wild, impossible Amy, it is that you never tell her what to do. It only makes her want to do the opposite. He could drop her off in Leadworth without another word and she would find a way back, just to spite him. No, no, she will never leave, not unless it's her idea.
So they formulate a plan. It is not a particularly complex one. No, far from it, actually. It's simple, easy, but it'll do the trick.
It is not difficult, picking an argument with Rory. Even less to provoke Amy; she has always had a bit of a temper, honestly. No, those are the easy bits. The hard part, the part that kills him, is the way he treats her.
"Stay out of it, Amelia. This doesn't concern you."
He has yelled at her in the past, and the universe knows she has shouted at him before. They have little spats here and there – it is bound to happen when you spend as much time together as they do, after all – but never like this. No, usually one of them backs down. Usually one of them knows that the fighting is not worth it. Usually one of them is willing to put their friendship, their companionship, their entire relationship before a stupid fight. But not this time.
"Take us home," she says the words he has been waiting for at last.
And then, more than anything else, he wants to stop. He wants to hug her, grab her forehead and kiss it, and tell her he does not mean any of it. He doesn't want her to leave; they have been through so much, she means so much to him now. But he cannot do that. He knows he cannot. It's not right; it is not fair, not to her. Because she needs to go back now, needs to return to little, dull, normal Leadworth or she never will; because if she does not go back now, he really will ruin her life and he won't do that to her. Can't do that to her.
Once the TARDIS lands, Amy doesn't miss a beat. She doesn't 't stop to gather any of the things she has collected, does not pause to reconsider. No, she doesn't even give him a second glance. All she does is grab Rory's hand and drag him out. And he follows them; without stopping, without thinking about it, he follows them.
Because it cannot be this simple, this easy! No, not this time, not with her. His Amy – his beautiful, brave, fantastic Amy – is not meant to give up this easily. She is quick, she is clever, and she is brilliant. She's supposed to see through him at times like this. Getting rid of her is not meant to be this easy!
Only, it really seems to be.
He stops three steps outside of the TARDIS and watches them storm off. But not for long. No, not for long at all. He cannot bear the sight of seeing them leave him so easily, and he turns back before she can even reach her door. Maybe it is better this way, without a real goodbye. It will hurt less in the long run, he supposes.
He hears her before he can shut the door and spins on his heel. And sure enough, there she is, his magnificent Amy Pond. He smiles, because he doesn't have to think about it; he just knows that she has caught on. Probably not completely, but she has figured out that it was not real, not a bit of what he said. She never could let things be easy. No, not her, not his Amy Pond; simple and easy have never been her way. And as proud as it makes him, it breaks his hearts in the slightest.
"Amy, Amy, Amy," he mumbles as he steps to her and takes her head between his hands. "I should have known," he breathes, closing his eyes. "Amy – mad, impossible Amy – you always were clever. Clever Amelia Pond." He presses his forehead against hers.
And just like that, he lets her see everything; shows every last bit of his and Rory's plan. She already knows something isn't right so there's no point in hiding it now. If he doesn't tell her, she will just drag it out of Rory later and he cannot bear her knowing like that. She would murder him if he did; it won't matter how far away he is, because Amy – his brilliant, magnificent, stubborn Amy – will find a way to do it just to prove her point.
"Hey," he mumbles. He knows she won't answer. No, of course not. Not while her human brain is trying to comprehend everything. "Got'cha." He presses his lips against her forehead one last time before he steps back into the TARDIS. He doesn't dare linger; won't linger; can't linger. If he lingers, she will stop him. His Amy is too stubborn to let him go; she will fight him to the end. And he is afraid she will win. So no, lingering is most definitely not a good idea.
He has barely shut the door before she catches up. "No, no, no!" She screams and he all but runs to the controls. "Doctor, open the door." And even as far away as he is, he can hear her hands hitting the door. He starts the TARDIS up, setting the coordinates as far away as possible. "Doctor!" Her voice cracks with her scream.
His fingers tighten around the lever and he hesitates. Because it almost feels like he is betraying her; leaving her here, in this awful village. She hates it here, he knows she does. Only he knows she doesn't. As dull as it is, it's her home, it's her life. As much as it will kill her for him to do this, he knows she will survive. His Amy is too good, too bright, too strong to not survive. More than survive, really. She will live. Maybe not the way she wants, but the way she needs. And he can't take that from her; won't take that from her.
He pulls the lever and sends the TARDIS off.
Afterwards, he's not sure how long he stands there, his head bent and his hands on the controls. It is too long, too short for the Time Lord to know. Because this is it, this is the start; the start of his new time alone. It's not the first time he has left a companion and it will not be the last. But still, still… it feels like the end. The end of his time with his Amy – his brave, clever, magnificent Amelia Pond. Finally, he lets go and steps away.
With a deep breath, he walks away and into the depths of the TARDIS.
"You will see the Doctor's life change forever, you will gasp in astonishment at the true nature of his relationship with Amy, and you will cry out in horror as Rory Williams stumbles to the brink of a tragic mistake." – Steven Moffat
Note: The original plan was only to have it in Amy's point of view, but Eleven really wanted his story to be told, too. I found the quote online when I was looking up season six and knew that I had to put it on here. Thanks to Muffintine for beta-ing.
Review, please.


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I have been making home made jerky for a while now and the other day I tried Hi-country Original Recipe Jerky Seasoning and I must say its instruction where easy to use and most important it made very tasty. I would recommend it to anyone who loves making home made jerky like I do.
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This stuff is absolute garbage. First, it did nothing to protect my nails from chipping. They chipped the same day as I applied the polish. Secondly, after few month the top coat got all gunky. When I would dip the brush in the bottle little strings of polish would come out (looked like hot glue from the gun). It would get all over my hands and nails.
This is the only top coat I use now. People often think I have shellac on my nails when I use this! It dries quickly, and the colour keeps on my nails twice as long when compared to not using a top coat at all. I am a JULEP maven member, and buy large quantities of this when they have 40% or 50% off sales. I then add a bottle into everyone's Christmas gift!
LOVE IT, LOVE IT, LOVE IT!! I love painting my nails but because I have soft nails, it usually lasts a whooping 6 hours before something chips and I'll have at least one smudge as I apparently can't hold still long enough for my nail polish to dry.
This top coat helps both of those problems. This top coat is nice and thick and after applying it, your nails dry almost instantly. It also leaves an almost shellac-type feel.
The Julep nail polish along with this top coat means I get several days of great looking nails and I will forever be a fan of this product.
I heard lots about this. I was expecting a lot more from the product. the nail polish chipped after a day using this
I got these for my daughter! She loved it!
LOVE JULEP, this is my favorite top coat to prevent shrinkage I wipe my nails with vinegar before applying the base coat stops shrinkage!
I love the high intensity shine this product gives my nails! The perfect finishing touch...for that salon finish at home!
I love this top coat from Julep! It is definitely my go to top coat! When I use it, my polish stays for at least a week!
I really wanted to like this product because I love Julep products. Unfortunately, this top coat actually shrunk when it dried, and lifted up my nail polish underneath. It ruined my manicures, and it got really thick and gloopy quickly.
This top coat is wonderful. Goes on smooth, dries quickly and seals in the polish..
These reviews are the subjective opinions of ChickAdvisor members and not of ChickAdvisor Inc.


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"Provence" has more efficacy as a "brand" than as a place. One rarely if ever hears any residents of the Vaucluse say that they live in "Provence." The word is heard frequently in its adjectival form: provençal.
As geography, the term "Provence" suffers abuse. The French consider contemporary 'Provence' to take in three administrative department:
- Vaucluse
- Bouches-du-Rhône
- Alpes-de-Haute-Provence
Confusion pops up due to the administrative region PACA: Provence-Alpes-Côte d'Azur.
When "Provence" is employed for the department of the Var (Toulon, St, Tropez) or the department of the Alpes-Maritime (Côte d'Azur) or even the five departments of the Languedoc-Roussillon, it is the "brand" asserting itself.
This is a regional distinction that Peter Mayle buys into 100% in his book Provence A-Z. In fact, if Mayle had been 'geographically-correct,' his iconic best seller would have been titled "A Year in the Luberon."
The Luberon and the Comtat Venaissin, referred to as the "Comtat," are the two large regions within the Vaulcuse,
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Mane: Dominique Paulin – A Painter Manifests Her Dreamy Inspirations at Une Soirée Bouche Bée; Exhibit Runs Until Aug. 30
From a solitary two-story concrete structure adrift on a wooded mountain top under a powder blue sky save where far over distant hills lies a mass of almost pure white clouds illumined by a band of gold light from the … Continue reading
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