bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simultaneous alignment and clustering of peptide data using a Gibbs sampling approach
Authors: Andreatta Massimo , Lund Ole , Nielsen Morten 
Published: October 2012

Abstract
Motivation: Proteins recognizing short peptide fragments play a central role in cellular signaling. As a result of high-throughput technologies, peptide-binding protein specificities can be studied using large peptide libraries at dramatically lower cost and time. Interpretation of such large peptide datasets, however, is a complex task, especially when the data contain multiple receptor binding motifs, and/or the motifs are found at different locations within distinct peptides.
Results: The algorithm presented in this article, based on Gibbs sampling, identifies multiple specificities in peptide data by performing two essential tasks simultaneously: alignment and clustering of peptide data. We apply the method to de-convolute binding motifs in a panel of peptide datasets with different degrees of complexity spanning from the simplest case of pre-aligned fixed-length peptides to cases of unaligned peptide datasets of variable length. Example applications described in this article include mixtures of binders to different MHC class I and class II alleles, distinct classes of ligands for SH3 domains and sub-specificities of the HLA-A*02:01 molecule.
Availability: The Gibbs clustering method is available online as a web server at http://www.cbs.dtu.dk/services/GibbsCluster.
Contact: massimo@cbs.dtu.dk
Supplementary information: Supplementary data are available at Bioinformatics online.
A method for integrative structure determination of protein-protein complexes
Authors: Schneidman-Duhovny Dina , Rossi Andrea , Avila-Sakar Agustin , Kim Seung Joong , Velázquez-Muriel Javier , Strop Pavel , Liang Hong , Krukenberg Kristin A. , Liao Maofu , Kim Ho Min , Sobhanifar Solmaz , Dötsch Volker , Rajpal Arvind , Pons Jaume , Agard David A. , Cheng Yifan , Sali Andrej 
Published: October 2012

Abstract
Motivation: Structural characterization of protein interactions is necessary for understanding and modulating biological processes. On one hand, X-ray crystallography or NMR spectroscopy provide atomic resolution structures but the data collection process is typically long and the success rate is low. On the other hand, computational methods for modeling assembly structures from individual components frequently suffer from high false-positive rate, rarely resulting in a unique solution.
Results: Here, we present a combined approach that computationally integrates data from a variety of fast and accessible experimental techniques for rapid and accurate structure determination of protein–protein complexes. The integrative method uses atomistic models of two interacting proteins and one or more datasets from five accessible experimental techniques: a small-angle X-ray scattering (SAXS) profile, 2D class average images from negative-stain electron microscopy micrographs (EM), a 3D density map from single-particle negative-stain EM, residue type content of the protein–protein interface from NMR spectroscopy and chemical cross-linking detected by mass spectrometry. The method is tested on a docking benchmark consisting of 176 known complex structures and simulated experimental data. The near-native model is the top scoring one for up to 61% of benchmark cases depending on the included experimental datasets; in comparison to 10% for standard computational docking. We also collected SAXS, 2D class average images and 3D density map from negative-stain EM to model the PCSK9 antigen–J16 Fab antibody complex, followed by validation of the model by a subsequently available X-ray crystallographic structure.
Availability: http://salilab.org/idock
Contact: dina@salilab.org or sali@salilab.org
Supplementary information: Supplementary data are available at Bioinformatics online.
United States Anesthesiologists over 50
Authors: Orkin Fredrick K. , McGinnis Sandra L. , Forte Gaetano J. , Peterson Mary Dale , Schubert Armin , Katz Jonathan D. , Berry Arnold J. , Cohen Norman A. , Holzman Robert S. , Jackson Stephen H. , Martin Donald E. , Garfield Joseph M. 
Published: October 2012

Background
Anesthesiology is among the medical specialties expected to have physician shortage. With little known about older anesthesiologists' work effort and retirement decision making, the American Society of Anesthesiologists participated in a 2006 national survey of physicians aged 50-79 yr.

Methods
Samples of anesthesiologists and other specialists completed a survey of work activities, professional satisfaction, self-defined health and financial status, retirement plans and perspectives, and demographics. A complex survey design enabled adjustments for sampling and response-rate biases so that respondents' characteristics resembled those in the American Medical Association Physician Masterfile. Retirement decision making was modeled with multivariable ordinal logistic regression. Life-table analysis provided a forecast of likely clinical workforce trends over an ensuing 30 yr.

Results
Anesthesiologists (N = 3,222; response rate = 37%) reported a mean work week of 49.4 h and a mean retirement age of 62.7 yr, both values similar to those of other older physicians. Work week decreased with age, and part-time work increased. Women worked a shorter work week (mean, 47.9 vs. 49.7 h, P = 0.024), partly due to greater part-time work (20.2 vs. 13.1%, P value less than 0.001). Relative importance of factors reported among those leaving patient care differed by age cohort, subspecialty, and work status. Poor health was cited by 64% of anesthesiologists retiring in their 50s as compared with 43% of those retiring later (P = 0.039).

Conclusions
This survey lends support for greater attention to potentially modifiable factors, such as workplace wellness and professional satisfaction, to prevent premature retirement. The growing trend in part-time work deserves further study.
Dynamic Changes in the Distribution of Minerals in Relation to Phytic Acid Accumulation during Rice Seed Development
Authors: Iwai Toru , Takahashi Michiko , Oda Koshiro , Terada Yasuko , Yoshida Kaoru T. 
Published: October 2012

Abstract
Phytic acid (inositol hexakisphosphate [InsP6]) is the storage compound of phosphorus in seeds. As phytic acid binds strongly to metallic cations, it also acts as a storage compound of metals. To understand the mechanisms underlying metal accumulation and localization in relation to phytic acid storage, we applied synchrotron-based x-ray microfluorescence imaging analysis to characterize the simultaneous subcellular distribution of some mineral elements (phosphorus, calcium, potassium, iron, zinc, and copper) in immature and mature rice (Oryza sativa) seeds. This fine-imaging method can reveal whether these elements colocalize. We also determined their accumulation patterns and the changes in phosphate and InsP6 contents during seed development. While the InsP6 content in the outer parts of seeds rapidly increased during seed development, the phosphate contents of both the outer and inner parts of seeds remained low. Phosphorus, calcium, potassium, and iron were most abundant in the aleurone layer, and they colocalized throughout seed development. Zinc was broadly distributed from the aleurone layer to the inner endosperm. Copper localized outside the aleurone layer and did not colocalize with phosphorus. From these results, we suggest that phosphorus translocated from source organs was immediately converted to InsP6 and accumulated in aleurone layer cells and that calcium, potassium, and iron accumulated as phytic acid salt (phytate) in the aleurone layer, whereas zinc bound loosely to InsP6 and accumulated not only in phytate but also in another storage form. Copper accumulated in the endosperm and may exhibit a storage form other than phytate.
Genetic identification of Iberian rodent species using both mitochondrial and nuclear loci: application to noninvasive sampling
Authors: Barbosa S. , Pauperio J. , Searle J. B. , Alves P. C. 
Published: October 2012

AbstractSpecies identification through noninvasive sampling is increasingly used in animal conservation genetics, given that it obviates the need to handle free‐living individuals. Noninvasive sampling is particularly valuable for elusive and small species such as rodents. Although rodents are not usually assumed to be the most obvious target for conservation, of the 21 species or near‐species present in Iberia, three are considered endangered and declining, while several others are poorly studied. Here, we develop a genetic tool for identifying all rodent species in Iberia by noninvasive genetic sampling. To achieve this purpose, we selected one mitochondrial gene [cytochrome b (cyt‐b)] and one nuclear gene [interphotoreceptor retinoid‐binding protein (IRBP)], which we first sequenced using tissue samples. Both genes allow for the phylogenetic distinction of all species except the sibling species Microtus lusitanicus and Microtus duodecimcostatus. Overall, cyt‐b showed higher resolution than IRBP, revealing a clear barcoding gap. To allow these markers to be applied to noninvasive samples, we selected a short highly diagnostic fragment from each gene, which we used to obtain sequences from faeces and bones from owl pellets. Amplification success for the cyt‐b and IRBP fragment was 85% and 43% in faecal and 88% and 64% in owl‐pellet DNA extractions, respectively. The method allows the unambiguous identification of the great majority of Iberian rodent species from noninvasive samples, with application in studies of distribution, spatial ecology and population dynamics, and for conservation.
School motivation and high school dropout: The mediating role of educational expectation
Authors: Fan Weihua , Wolters Christopher A. 
Published: October 2012

BackgroundA good deal of evidence indicates that students' motivational beliefs and attitudes play a critical role in their academic success. Research studies on how motivational factors may help determine whether students remain in high school or drop out, however, are relatively few. More specifically, there is a lack of research examining the dynamics of whether students' motivational beliefs from earlier in high school might be used to predict their status as a dropout in their final year.AimsThe aim of the present study was to examine the mediating role of students' educational expectations in linking students' school motivation to their dropout status by utilizing a nationally representative dataset.SampleThe present study used data from the Educational Longitudinal Study of 2002 (ELS: 2002). The final sample consisted of 16,194 students, with approximately 54% White, 13% Black, 16% Hispanic, and 10% Asian students, and the rest were Native American, Hawaiian, multiracial, or of other races.MethodStructural equation modelling was employed to conduct the mediational analysis.ResultsThe results of the present study demonstrated that the relationships between student ability beliefs in math and English and student behaviour of dropping out were fully mediated by students' educational expectations. The results also revealed that student intrinsic value in math and English had significant indirect relations with student behaviour of leaving school through students' educational expectations.ConclusionsThe results of this study suggest that explanations for student dropout status that rely solely on students' social background and school behaviours without considering their motivation are incomplete. The study expands the extant research by showing possible pathways that motivate students to persist in high school. These pathways are specifically rooted in students' ability beliefs and intrinsic interest in learning through their relationships with students' expectations for their education.
Social support and trait personality are independently associated with resting cardiovascular function in women
Authors: Creaven Ann‐Marie , Howard Siobhán , Hughes Brian M. 
Published: October 2012

ObjectivesSocial support is thought to positively influence appraisals of stressors and coping resources, thereby attenuating the harmful effects of stress. Notably, perceived available support (rather than actually received support) is believed to benefit well‐being independent of the sense of obligation or threats to self‐esteem that receiving support may entail. This study examined whether perceived support levels were associated with reduced cardiovascular levels, an important predictor of cardiovascular disease risk, independent of broad trait personality variables frequently reported to overlap with perceived support. In doing so, we sought to determine whether the effects of perceived support are independent of links between personality and social support.DesignA cross‐sectional design was employed.MethodsResting cardiovascular levels were measured using a Finometer in a sample of healthy women (N = 145). The Short‐Form Social Support Questionnaire and the Revised Eysenck's Personality Questionnaire were used to assess support levels and personality. Regression was used to compare associations with psychometric indices of support (namely, perceived network size and perceived satisfaction with support) and personality (psychoticism, extraversion and neuroticism).ResultsSupport independently predicted systolic blood pressure (SBP; p = .03) and HR (p = .02) when personality was controlled for, while personality also predicted SBP (p = .01) and DBP (p = .02). Support effects were not mediated by personality.ConclusionsThe findings corroborate previous research indicating links between support and resting cardiovascular levels and additionally demonstrate these to be independent of associations between support and personality.Statement of contributionWhat is already known on this subject? Social support is known to have several physical health benefits particularly for cardiovascular function. Studies have demonstrated psychometrically assessed support to predict reduced resting cardiovascular levels. Other work links support significantly with trait personality, particularly extraversion and neuroticism.What does this study add? Corroborating previous studies, social support was associated with reduced systolic blood pressure and heart rate. Importantly, these results remained robust to controlling for trait personality. The effects of support on cardiovascular levels are independent of personality influences on social support levels.
Defining the impact of individual sample variability on routine immunoassay of serum free light chains (sFLC) in multiple myeloma
Authors: Murng S H K , Follows L , Whitfield P , Snowden J A , Swallow K , Green K , Sargur R , Egner W 
Published: October 2012

Summary
Serum free light chain (sFLC) measurement has gained widespread acceptance and is incorporated into various diagnostic and response criteria. Non-linearity and antigen excess are the main causes of ‘variability’ in the measurement of sFLC using immunoassay, but the impact of these on measurement has been unclear. We performed a retrospective evaluation using a dilutional strategy to detect these phenomena. A total of 464 samples in 2009 and 373 samples in 2010 were analysed for sFLC. Non-linearity was detected in both high and apparently normal sFLC. Major non-linearity of more than twofold is common in high kappa (20·2%) and lambda (14·1%). It is less common in samples with apparently normal levels – kappa (6·4%) and lambda (9·5%). 9·4% of kappa and 15·5% of lambda showed antigen excess at screening dilutions. 34·4% of the samples had either non-linearity or antigen excess. We conclude that significant measurement variability is common in the measurement of sFLC. There is currently no reliable technique to detect non-linearity phenomena unless a serial dilution strategy is applied to every analysis. We recommend that laboratories routinely reporting sFLC results for clinical services need appropriate strategies for addressing these issues. Clinicians should be aware of these limitations in interpretation of sFLC assay for individual patients. Future guidelines should adopt action thresholds which are grounded firmly in test performance parameters.
A report of two novel NR5A1 mutation families: possible clinical phenotype of psychiatric symptoms of anxiety and/or depression
Authors: Suwanai Ayuko S. , Ishii Tomohiro , Haruna Hidenori , Yamataka Atsuyuki , Narumi Satoshi , Fukuzawa Ryuji , Ogata Tsutomu , Hasegawa Tomonobu 
Published: October 2012

SummaryObjectiveNR5A1 or steroidogenic factor 1 is a nuclear receptor that plays important roles in the hypothalamus–pituitary–steroidogenic axis. The clinical phenotype of most 46,XY mutation carriers includes disorders of sex development (DSD) without adrenal insufficiency, whereas 46,XX mutation carriers have phenotypes ranging from no symptoms to ovarian insufficiency. Although genetically engineered ventromedial hypothalamus‐specific Nr5a1 knockout mice show anxiety behaviour, no psychiatric symptoms have been reported in human NR5A1 mutation carriers. We report clinical and molecular findings for individuals (from two families) with NR5A1 mutations, showing psychiatric symptoms.Design and methodsWe screened for NR5A1 mutations in a cohort of 34 patients with 46,XY DSD using PCR‐based sequencing. Psychiatric symptoms were assessed using mental health assessment tools and structured clinical interviews. Functional properties of detected mutant NR5A1s were studied in silico and in vitro, including three‐dimensional (3D) mutation models, subcellular NR5A1 protein localization and transactivation assays.ResultsWe found 2 (46,XY) patients with NR5A1 heterozygous novel mutations (p.D257fs and p.V424del), which were transmitted from their respective mothers. The patients' clinical findings indicated DSD without adrenal insufficiency. Both mothers showed psychiatric symptoms, including excessive anxiety and/or depression. The mother and grandmother of one patient had premature ovarian insufficiency. Functional studies showed altered 3D models of p.V424del and normal subcellular NR5A1 localization and impaired transcriptional activation without dominant‐negative effects in both mutations.ConclusionsWe found 2 (46,XX) NR5A1 mutation carriers with excessive anxiety and/or depression. These results suggest that excessive anxiety and/or depression are possible clinical phenotypes of 46,XX NR5A1 mutations.
Inheritance of the chronic myeloproliferative neoplasms. A systematic review
Authors: Ranjan A , Penninga E , Jelsig AM , Hasselbalch HC , Bjerrum OW 
Published: October 2012

Ranjan A, Penninga E, Jelsig AM, Hasselbalch HC, Bjerrum OW. Inheritance of the chronic myeloproliferative neoplasms. A systematic review.This systematic review investigated the inheritance of the classical chronic myeloproliferative neoplasms (MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) and chronic myelogenous leukemia (CML). Sixty‐one articles were included and provided 135 families with a total of 341 participants distributed to various subtypes of MPN: 50% PV, 23% ET, 14% PMF, 10% CML and 3% non‐MPN hematological disorder. Women developed the disease earlier than men (43.1 years vs 47.3 years; p = 0.074), while the general average age of onset was 46 years, notably younger than sporadic cases. The clinical phenotype of the families showed a homogenous (67%) and a heterogeneous (33%) pattern, with the majority being PV–PV pairs (36%) and PV–PMF pairs (17%), respectively. This observation suggests that the susceptibility gene (or genes) is not restricted to one subtype supporting the hypothesis of a mutation in an early multipotent stem cell. Furthermore, a major subgroup of families provided evidence of an autosomal dominant (AD) inheritance with reduced penetrance. This study suggests that the origin of MPNs may occur in at least three different settings: (i) a sporadic, (ii) genetic heterogeneity with polygenetic and environmental impact and (iii) a familial phenotype following an AD inheritance.
Does Grammatical Aspect Affect Motion Event Cognition? A Cross‐Linguistic Comparison of English and Swedish Speakers
Authors: Athanasopoulos Panos , Bylund Emanuel 
Published: October 2012

AbstractIn this article, we explore whether cross‐linguistic differences in grammatical aspect encoding may give rise to differences in memory and cognition. We compared native speakers of two languages that encode aspect differently (English and Swedish) in four tasks that examined verbal descriptions of stimuli, online triads matching, and memory‐based triads matching with and without verbal interference. Results showed between‐group differences in verbal descriptions and in memory‐based triads matching. However, no differences were found in online triads matching and in memory‐based triads matching with verbal interference. These findings need to be interpreted in the context of the overall pattern of performance, which indicated that both groups based their similarity judgments on common perceptual characteristics of motion events. These results show for the first time a cross‐linguistic difference in memory as a function of differences in grammatical aspect encoding, but they also contribute to the emerging view that language fine tunes rather than shapes perceptual processes that are likely to be universal and unchanging.
Lack of drug–drug interaction between empagliflozin, a sodium glucose cotransporter 2 inhibitor, and warfarin in healthy volunteers
Authors: Macha S. , Rose P. , Mattheus M. , Pinnetti S. , Woerle H. J. 
Published: October 2012

AimTo investigate potential drug–drug interactions between empagliflozin and warfarin.MethodsHealthy subjects (n = 18) received empagliflozin 25 mg qd for 5 days (treatment A), followed by empagliflozin 25 mg qd for 7 days (days 6–12) with a single 25 mg dose of warfarin on day 6 (treatment B), and a single 25 mg dose of warfarin alone (treatment C), in an open‐label, crossover study. Subjects received treatments in sequence AB_C or C_AB with a washout period of ≥14 days between AB and C or C and AB.ResultsWarfarin had no effect on empagliflozin area under concentration‐time curve or maximum plasma concentration at steady‐state (AUCτ,ss or Cmax,ss): geometric mean ratios (GMRs) (90% confidence intervals [CI]) were 100.89% (96.86, 105.10) and 100.64% (89.79, 112.80), respectively. Empagliflozin had no effect on AUC from 0 h to infinity (AUC0–∞) or Cmax for R‐ or S‐warfarin (GMRs [90% CI] for AUC0–∞: 98.49% [95.29, 101.80] and 95.88% [93.40, 98.43], respectively; Cmax: 97.89% [91.12, 105.15] and 98.88% [91.84, 106.47], respectively). Empagliflozin had no clinically relevant effects on warfarin's anticoagulant activity (international normalised ratio [INR]) (GMR [95% CI] for peak INR: 0.87 [0.73, 1.04]; area under the effect‐time curve from 0 to 168 h: 0.88 [0.79, 0.98]. No drug‐related adverse events were reported for empagliflozin after monotherapy or combined administration. The combination of empagliflozin and warfarin was well tolerated.ConclusionsNo drug–drug interactions were observed between empagliflozin and warfarin, indicating that empagliflozin and warfarin can be co‐administered without dosage adjustments of either drug.