tbuckley/cabot-search huggingface dataset:
An Update of DIVERGE Software for Functional Divergence Analysis of Protein Family
Authors: Xun Gu, Yangyun Zou, Zhixi Su, Wei Huang, Zhan Zhou, Zebulun Arendsee, Yanwu Zeng
Journal: Molecular Biology and Evolution (2013)

DIVERGE is a software system for phylogeny-based analyses of protein family evolution and functional divergence. It provides a suite of statistical tools for selection and prioritization of the amino acid sites that are responsible for the functional divergence of a gene family. The synergistic efforts of DIVERGE and other methods have convincingly demonstrated that the pattern of rate change at a particular amino acid site may contain insightful information about the underlying functional divergence following gene duplication. These predicted sites may be used as candidates for further experiments. We are now releasing an updated version of DIVERGE with the following improvements: 1) a feasible approach to examining functional divergence in nearly complete sequences by including deletions and insertions (indels); 2) the calculation of the false discovery rate of functionally diverging sites; 3) estimation of the effective number of functional divergence-related sites that is reliable and insensitive to cutoffs; 4) a statistical test for asymmetric functional divergence; and 5) a new method to infer functional divergence specific to a given duplicate cluster. In addition, we have made efforts to improve software design and produce a well-written software manual for the general user.
An unusual ending to an anatomy lesson
Authors: Janet Cornwall
Journal: BMJ (2006)

We thank those who helped us identify comparable statistics with England for Wales and Northern Ireland and explained that no such statistics are available for Scotland.Also thanks to Olly Bevan for assembling the statistical material.Contributors and sources: The evidence and ideas for this paper come from GB's involvement in the development of NHS star ratings in England and CH's extensive research into regulation by governments in various sectors.The article
Are Obesity-Related Metabolic Risk Factors Modulated by the Degree of Insulin Resistance in Adolescents?
Authors: Fida Bacha, Rola Saad, Neslihan Gungor, Silva A. Arslanian
Journal: Diabetes Care (2006)

Obesity is often associated with insulin resistance and the components of the metabolic syndrome. However, wide variations in insulin sensitivity are noted in obese youth. It is not clear if greater insulin resistance confers a higher risk of cardiovascular comorbidities and risk for type 2 diabetes.We investigated physical and metabolic features of 54 obese adolescents. Subsequently, we pair matched 17 moderately insulin-resistant (MIR group) to 17 severely insulin-resistant (SIR group) youth based on cut points for insulin sensitivity (MIR group insulin sensitivity within 2 SDs and SIR group <2 SDs of normal-weight adolescent values). We evaluated differences in body composition (dual-energy X-ray absorptiometry), abdominal fat (computed tomography scan), cardiorespiratory fitness (CRF) (Vo(2max) on a treadmill), insulin sensitivity and secretion (hyperinsulinemic-euglycemic and hyperglycemic clamps), substrate utilization (indirect calorimetry), and fasting adiponectin and lipid profile.SIR youth had higher visceral adiposity (78.3 +/- 6.9 vs. 60.3 +/- 6.9 cm(2), P = 0.017) and waist-to-hip ratio (0.91 +/- 0.01 vs. 0.86 +/- 0.02, P = 0.026) and lower HDL (1.0 +/- 0.03 vs. 1.16 +/- 0.06 mmol/l, P = 0.015) than pair-matched MIR subjects. There was a tendency for adiponectin (6.1 +/- 0.5 vs. 8.6 +/- 1.1 microg/ml, P = 0.079) and CRF (49.9 +/- 3.2 vs. 55.2 +/- 3.5 ml x min(-1) x kg(-1) fat-free mass, P = 0.09) to be lower in SIR subjects. SIR youth also had an impaired balance between insulin sensitivity and beta-cell compensation with a lower glucose disposition index.Despite similar BMI, the degree of insulin resistance impacts the risk for obesity-related metabolic comorbidities. The SIR youth are at greater risk for type 2 diabetes and cardiovascular disease.
<i>TOLL</i>-like Receptor 10 Genetic Variation Is Associated with Asthma in Two Independent Samples
Authors: Ross Lazarus, Benjamin A. Raby, Christoph Lange, Edwin K. Silverman, David J. Kwiatkowski, Donata Vercelli, Walt J. Klimecki, Fernando D. Martinez, Scott T. Weiss
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

TOLL-like receptor 10 (TLR10) is the most recently identified human homolog of the Drosophila TOLL protein. In humans, the TOLL-like receptors recognize pathogen-associated molecular patterns (PAMPs) as part of innate immune host defenses. Localized to chromosome 4p14, the specific ligands and functions of TLR10 are currently unknown, although it is expressed in lung and in B-lymphocytes. TLR10 is a potential asthma candidate gene because early life innate immune responses to ubiquitous inhaled allergens and PAMPs may influence asthma susceptibility. Resequencing in 47 subjects revealed a total of 78 single nucleotide polymorphisms (SNPS) (1 SNP per 106 bp) of which only 11 had been previously published. A significant association (p < or = 0.02) between two SNPs (c.+1031G>A, c.+2322A>G) and physician-diagnosed asthma was observed in a case control study (517 cases, 519 control subjects) of European American subjects nested within the Nurses' Health Study cohort. The association for these same two SNPs (p < or = 0.015) replicated in an independent family based cohort, where a measure of airway hyperresponsiveness (PC20) was also associated (p = 0.026 for c.+1031G>A). Consistent association in two independent samples and association with an intermediate phenotype provides strong support for TLR10 genetic variation contributing to asthma risk.
(56) Solar urticaria
Authors: K.W. Scott
Journal: British Journal of Dermatology (1984)

Journal Article (56) Solar urticaria Get access K.W. Scott K.W. Scott Craigavon Area Hospital, Craigavon, Northern Ireland Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 111, Issue s26, 1 July 1984, Pages 105–106, https://doi.org/10.1111/j.1365-2133.1984.tb05326.x Published: 01 July 1984
Bicarbonate secretion of mouse cholangiocytes involves Na<sup>+</sup>-HCO<sub>3</sub><sup>−</sup>cotransport in addition to Na<sup>+</sup>-independent Cl<sup>−</sup>/HCO<sub>3</sub><sup>−</sup>exchange
Authors: Iker Uriarte, Jesús M. Banales, Elena Sáez, Fabián Arenas, Ronald P. J. Oude Elferink, Jesús Prieto, Juan F. Medina
Journal: Hepatology (2009)

Bicarbonate secretion from cholangiocytes is required for appropriate adjustment of primary canalicular bile along the biliary tract. In human and rat cholangiocytes, bicarbonate secretion is mediated by anion exchanger (AE) 2, an electroneutral Na+-independent Cl−/HCO3 − AE also involved in intracellular pH (pHi) regulation. In Ae2a,b -deficient mice, pHi is increased in lymphocytes and fibroblasts, whereas it is surprisingly normal in cholangiocytes. Here, we analyze the mechanisms for HCO3 − secretion in cultured Ae2a,b +/+ and Ae2a,b −/− mouse cholangiocytes by microfluorimetric measurement of pHi changes upon established perfusion maneuvers. Cl− withdrawal by isethionate-based perfusions showed that Ae2a,b +/+ but not Ae2a,b −/− mouse cholangiocytes can display Cl−/HCO3 − exchange, which is therefore entirely mediated by Ae2. Nevertheless, simultaneous withdrawal of Cl− and Na+ revealed that mouse cholangiocytes possess an additional transport activity for HCO3 − secretion not observed in control rat cholangiocytes. Propionate-based maneuvers indicated that this supplemental Na+-driven HCO3 −-secreting activity is Cl−-independent, consistent with a Na+-HCO3 − cotransport (NBC). NBC activity is greater in Ae2a,b −/− than Ae2a,b +/+ mouse cholangiocytes, and membrane-depolarization experiments showed that it is electrogenic. Consistent with the potential role of Slc4a4/Nbc1 as the involved transporter, Ae2a,b −/− mouse cholangiocytes exhibit up-regulated expression of this electrogenic NBC carrier. Whereas Ae2-mediated Cl−/HCO3 − exchange in Ae2a,b +/+ mouse cholangiocytes is stimulated by cyclic adenosine monophosphate (cAMP) and acetylcholine, the NBC activity is down-regulated by cAMP and adenosine triphosphate (ATP) in Ae2a,b −/− mouse cholangiocytes. Polarized Ae2a,b −/− mouse cholangiocytes placed in Ussing chambers show decreased (but not abolished) cAMP-dependent Cl− current and increased ATP-dependent/Ca2+-activated Cl− secretion, which run in parallel with decreased cystic fibrosis transmembrane conductance regulator messenger RNA expression and increased intracellular Ca2+ levels. Conclusion : Bicarbonate secretion in mouse cholangiocytes involves two differentially regulated activities: Ae2-mediated Cl−/HCO3 − exchange and Na+-HCO3 − cotransport. (Hepatology 2009.)
The PHF11 gene is not associated with asthma or asthma phenotypes in two independent populations
Authors: J McClenaghan, N M Warrington, E F Jamrozik, J Hui, J P Beilby, J Hansen, N H de Klerk, A L James, A W Musk, L J Palmer
Journal: Thorax (2009)

<h3>Background:</h3> Numerous areas of the human genome have previously been associated with asthma and asthma-related phenotypes, but few positive findings have been successfully replicated in independent populations. Initial studies have reported strong associations of variants in the plant homeodomain zinc finger protein 11 (<i>PHF11</i>) gene with serum IgE levels, asthma, airway hyper-responsiveness and childhood atopic dermatitis. <h3>Objectives:</h3> To investigate the association of variants in the <i>PHF11</i> gene with asthma and associated intermediate phenotypes in two independent Western Australian population-based samples. <h3>Methods:</h3> A linkage-disequilibrium (LD)-tagging set of 20 single nucleotide polymorphisms (SNPs) was genotyped in <i>PHF11</i> in two separate populations (total n = 2315), a family-based twin study consisting of 230 families (n = 992 subjects) and a population-based nested case-control study consisting of 617 asthma cases and 706 controls. Information regarding asthma, respiratory physiology, atopy and environmental exposures was collected. Transmission disequilibrium tests, variance components models and generalised linear models were used to test for association between <i>PHF11</i> SNPs and selected asthma outcomes (including longitudinal change in lung function). <h3>Results:</h3> After correction for multiple testing, no statistically significant (p&lt;0.05) associations were found between <i>PHF11</i> and either asthma or total serum IgE levels in either population. No statistically significant associations were found with any other asthma-associated phenotypes in either population. <h3>Conclusions:</h3> Previously reported associations of <i>PHF11</i> with asthma outcomes were not replicated in this study. This study suggests that <i>PHF11</i> is unlikely to contain polymorphic loci that have a major impact on asthma susceptibility in our populations.
Adult respiratory distress syndrome: has there been a change in outcome predictive measures?
Authors: J Lee, J S Turner, C J Morgan, B F Keogh, T W Evans
Journal: Thorax (1994)

BACKGROUND--Studies suggest that the mortality in adults with acute respiratory distress (ARDS) has not changed over the past two decades, despite the introduction of new therapeutic techniques and sophisticated ventilatory support devices. Mortality and physiological variables that might predict outcome in patients with ARDS were therefore assessed. METHODS--A retrospective survey was undertaken in 41 patients with ARDS. RESULTS--Mortality was 66%. Only the presence of sepsis predicted death. CONCLUSION--Mortality from ARDS is unchanged. Currently available severity scoring systems are not helpful in predicting outcome.
Severe breathlessness, mouth ulcers and skin blistering in a female
Authors: V.S. Gudi
Journal: European Respiratory Journal (2004)

Case historyA 63-yr-old housewife was referred in August 2001 with a 10-yr history of gradually worsening breathlessness on exertion, cough and repeated respiratory tract infections.She had never smoked.She had been diagnosed with follicular B-cell non-Hodgkin9s lymphoma 10 yrs previously, which was treated with chemotherapy, including chlorambucil, vincristine and prednisolone, and subsequent radiotherapy for intra-abdominal recurrence.A year after the diagnosis of malignancy, she was seen in the local dermatology unit with a blistering eruption on her legs and oral mucosa, which was subsequently confirmed by skin biopsy and immunofluorescence studies to be bullous pemphigoid.She developed muscle weakness due to myasthenia gravis 2 yrs later.There was no evidence of an associated thymoma.Both her muscle and skin disease were controlled with oral corticosteroids and azathioprine, along with pyridostigmine, for nearly 10 yrs.In April 2001, her skin disease was further evaluated because of persistent oral ulceration; a diagnosis of paraneoplastic pemphigus (PNP) was confirmed by presence of circulating antibodies to a variety of intra-and extracellular epidermal antigens, including bullous pemphigoid antigen (230 kD), envoplakin (210 kD) and periplakin (190 kD).Physical examination showed the presence of inspiratory crackles at lung bases; there was no cyanosis or clubbing.
Differential uptake of myocardial perfusion radiotracers in normal, infarcted, and acutely ischemic peri-infarction myocardium
Authors: Juan Cinca, Amparo Garcia-Burillo, Ana Carreño, Juan Castell, Mark Warren, Jaume Candell-Riera, Ana Domingo, J Soler-Soler
Journal: Cardiovascular Research (1998)

Objectives: We measured the uptake of technetium-99m tetrofosmin (99mTc) and thallium-201 (201Tl) in areas of healed transmural myocardial infarction and in regions of acute peri-infarction ischemia. Methods: Anesthetised pigs with a 1-month old transmural infarction elicited by permanent ligature of the left anterior descending (LAD) coronary artery below the first branch underwent one hour of proximal LAD occlusion followed by injection of -tetrofosmin and either in the left atrium (GI, n=19) or in the jugular vein (GII, n=6). Twelve other pigs (GIII) with a similar acute peri-infarction ischemia received -tetrofosmin and into the left ventricle during cardiocirculatory arrest to rule out the effect of coronary collaterals. Radiotracer counting was determined in samples from normal, acute ischemic and necrotic regions. Results: Uptake of -tetrofosmin and was greater in the infarct scar (median % of normal tissue: 20 for and 8.6 for in GI; 22 and 15 in GII) than in acute ischemic myocardium (3.2 and 2.5 in GI; 6.4 and 3.3 in GII). Radiotracer injection in arrested hearts (GIII) depicted a similar pattern (median % of injected dose: 6.2 for and 10 for in the scar; 2.3 and 4.0 in acute ischemia; and 2.9 and 3.5 in normal tissue). The infarcted region showed connective tissue and lack of viable myocardium. Conclusions: A 1-month old infarct scar with no viable myocardial tissue can take up significant fractions of -tetrofosmin and even in the absence of coronary collateral perfusion. Data suggest that the infarct scar can extract these radiotracers from the intraventricular blood.
The Roles of Lipid Oxidation Products and Receptor Activator of Nuclear Factor-κB Signaling in Atherosclerotic Calcification
Authors: Linda Demer, Yin Tintut
Journal: Circulation Research (2011)

This review focuses on the roles of oxylipids and receptor activator of nuclear factor-κB ligand signaling in calcific cardiovascular disease. Both intimal and valvular calcifications are closely associated with atherosclerosis, leading investigators to study the role of atherogenic oxidatively modified lipids (oxylipids). Results have identified the molecular signaling through which oxylipids induce osteogenic differentiation and calcification in vascular cells. A surprising concomitant finding was that, in bona fide osteoblasts from skeletal bone, oxylipids have the opposite effect, ie, inhibiting osteoblastic maturation. This is the basis for the lipid hypothesis of osteoporosis. Oxylipids also induce resorptive osteoclastic cells within the bone environment, raising the question of whether resorptive osteoclasts can be harnessed in the vascular context for cell-based therapy to remove artery wall mineral deposits. The challenge is that vascular cells produce antiosteoclastogenic factors, including the soluble decoy receptor for receptor activator of nuclear factor-κB ligand, possibly accounting for the paucity of resorptive cells and the dominance of mineral in atherosclerotic plaque. These factors may have therapeutic use in osteoclastogenic removal of mineral deposits from arteries.
The Power to Detect Quantitative Trait Loci Using Resequenced, Experimentally Evolved Populations of Diploid, Sexual Organisms
Authors: James G. Baldwin-Brown, Anthony D. Long, Kevin R. Thornton
Journal: Molecular Biology and Evolution (2014)

A novel approach for dissecting complex traits is to experimentally evolve laboratory populations under a controlled environment shift, resequence the resulting populations, and identify single nucleotide polymorphisms (SNPs) and/or genomic regions highly diverged in allele frequency. To better understand the power and localization ability of such an evolve and resequence (E&R) approach, we carried out forward-in-time population genetics simulations of 1 Mb genomic regions under a large combination of experimental conditions, then attempted to detect significantly diverged SNPs. Our analysis indicates that the ability to detect differentiation between populations is primarily affected by selection coefficient, population size, number of replicate populations, and number of founding haplotypes. We estimate that E&R studies can detect and localize causative sites with 80% success or greater when the number of founder haplotypes is over 500, experimental populations are replicated at least 25-fold, population size is at least 1,000 diploid individuals, and the selection coefficient on the locus of interest is at least 0.1. More achievable experimental designs (less replicated, fewer founder haplotypes, smaller effective population size, and smaller selection coefficients) can have power of greater than 50% to identify a handful of SNPs of which one is likely causative. Similarly, in cases where s ≥ 0.2, less demanding experimental designs can yield high power.
Multicenter prospective trial evaluating the tolerability of imatinib for Japanese patients with chronic myelogenous leukemia in the chronic phase: Does body weight matter?
Authors: Yoshinobu Kanda, Shinichiro Okamoto, Tetsuzo Tauchi, Masahiro Kizaki, Koiti Inokuchi, Mariko Yabe, Kenji Yokoyama, Yoshikazu Ito, Yukihiko Kimura, Masaaki Higashihara, Masami Bessho, Kiyoshi Ando, Shigeru Chiba, Mineo Kurokawa, Kazuo Oshimi, Kazuo Dan, Kazuma Ohyashiki, Yasuo Ikeda
Journal: American Journal of Hematology (2008)

Imatinib at a daily dose of 400 mg is the standard treatment for chronic myelogenous leukemia in the chronic phase. However, the feasibility of this dose for small Japanese adults has not been clarified. We prospectively investigated the toxicity and efficacy of this dose in adult Japanese patients. Among the 89 evaluable patients with a median body weight of 62.8 kg, imatinib therapy was held in 40 subjects (45%), due to Grade 3-4 toxicities in 30 patients (75%) and Grade 2 toxicities at the discretion of the attending physician in 10 patients (25%). However, treatment was resumed and the dose was gradually increased until 62 of the 89 patients tolerated a maintenance dose of 400 mg. Older age and lower body weight were significant independent risk factors for discontinuation of imatinib. After a median follow-up period of 31 months, 84 patients were alive without progression. The complete cytogenetic response rate was 60 and 90% at 6 months and 1 year after starting imatinib, respectively. Older patients and those with a lower body weight were less likely to achieve a complete cytogenetic response. These findings suggest that the body weight has a significant influence on the toxicity and efficacy of imatinib in patients with a small body size, although dose reduction in proportion to weight may result in an inadequate response to imatinib.
Use of digital x ray radiogrammetry in the assessment of joint damage in rheumatoid arthritis
Authors: W B Jawaid
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To compare digital <i>x</i> ray radiogrammetry (DXR) with manual radiography for assessing bone loss in RA and examine the relationship of the scores obtained with other disease indices. <b>Methods:</b> 225 consecutive consenting subjects attending the RA clinic were enrolled. An <i>x</i> ray examination was carried out; demographic details recorded; a self assessment questionnaire completed; blood taken for ESR measurement; and an assessment made by a trained nurse. All <i>x</i> ray films were scored manually using the modified Sharp technique by a single observer; 20 films were rescored by three readers. Films were assessed with the Pronosco X-Posure system, version 2.0. Analysis included χ<sup>2</sup> tests, independent <i>t</i> tests, multiple linear regression, and partial correlations, as appropriate. The smallest detectable difference (SDD), coefficient of variation (CV), and coefficient of repeatability (CR) were determined from Bland and Altman plots. <b>Results:</b> The DXR precision varied: SDD = 0.002–0.9; CV = 0.09–5.9%; CR = 0.002–0.792, but was better than that of the intra- and interobserver Sharp scores: SDD = 73.9; CV = 27.8%; CR = 33.0–47.6. The DXR measurements, bone mineral density (<i>R</i><sup>2</sup> = 0.210), metacarpal index (<i>R</i><sup>2</sup> = 0.222), and cortical thickness (<i>R</i><sup>2</sup> = 0.215), significantly predicted Sharp scores. In women, DXR measurements significantly correlated with modified HAQ scores but with no other disease indices. Sharp scores significantly correlated with assessor's global assessment, swollen and tender joint counts, pain, HAQ, and DAS28. <b>Conclusion:</b> DXR measurements are more precise than Sharp scores; both are related to long term disease activity in RA. DXR is simple to use, does not require intensive training, and may identify subjects not responding to standard treatment.
TCT-429 Short- and intermediate- term clinical outcomes after implantation of everolimus-eluting bioresorbable scaffold in complex lesions : a prospective single-arm study - ABSORB Expand trial
Authors: Robert J. Van Geuns, Peter De Jaegere, Roberto Diletti, Antonios Karanasos, Takashi Muramatsu, Sjoerd T. Nauta, Yoshinobu Onuma, Evelyn Regar, Carl J. Schultz, Patrick W. Serruys, Nicolas M. Van Mieghem, Felix Zijlstra
Journal: Journal of the American College of Cardiology (2013)
Tumor markers in pancreatic cancer: a European Group on Tumor Markers (EGTM) status report
Authors: M.J. Duffy, C. Sturgeon, R. Lamerz, C. Haglund, V.L. Holubec, R. Klapdor, A. Nicolini, O. Topolcan, V. Heinemann
Journal: Annals of Oncology (2009)
Model-Based Influences on Humans' Choices and Striatal Prediction Errors
Authors: Nathaniel D. Daw, Samuel J. Gershman, Ben Seymour, Peter Dayan, Raymond J. Dolan
Journal: Neuron (2011)

The mesostriatal dopamine system is prominently implicated in model-free reinforcement learning, with fMRI BOLD signals in ventral striatum notably covarying with model-free prediction errors. However, latent learning and devaluation studies show that behavior also shows hallmarks of model-based planning, and the interaction between model-based and model-free values, prediction errors, and preferences is underexplored. We designed a multistep decision task in which model-based and model-free influences on human choice behavior could be distinguished. By showing that choices reflected both influences we could then test the purity of the ventral striatal BOLD signal as a model-free report. Contrary to expectations, the signal reflected both model-free and model-based predictions in proportions matching those that best explained choice behavior. These results challenge the notion of a separate model-free learner and suggest a more integrated computational architecture for high-level human decision-making.