bluuebunny/crossref_metadata_2025_split huggingface dataset:
Viruses selectively mutate their CD8+ T-cell epitopes—a large-scale immunomic analysis
Authors: Vider-Shalit Tal , Sarid Ronit , Maman Kobi , Tsaban Lea , Levi Ran , Louzoun Yoram 
Published: May 2009

Abstract
Motivation: Viruses employ various means to evade immune detection. One common evasion strategy is the removal of CD8+cytotoxic T-lymphocyte epitopes. We here use a combination of multiple bioinformatic tools and large amount of genomic data to compute the epitope repertoire presented by over 1300 viruses in many HLA alleles. We define the ‘Size of Immune Repertoire score’, which represents the ratio between the epitope density within a protein and the expected density. This score is used to study viral immune evasion.
Results: We show that viral proteins in general have a higher epitope density than human proteins. This difference is due to a good fit of the human MHC molecules to the typical amino-acid usage of viruses. Among different viruses, viruses infecting humans present less epitopes than non-human viruses. This selection is not at the amino-acid usage level, but through the removal of specific epitopes. Within a single virus, not all proteins express the same epitopes density. Proteins expressed early in the viral life cycle have a lower epitope density than late proteins. Such a difference is not observed in non-human viruses. The removal of early epitopes and the targeting of the cellular immune response to late viral proteins, allow the virus a time interval to propagate before its host cells are destroyed by T cells.
Contact: louzouy@math.biu.ac.il
Constrained mixture estimation for analysis and robust classification of clinical time series
Authors: Costa Ivan G. , Schönhuth Alexander , Hafemeister Christoph , Schliep Alexander 
Published: May 2009

Abstract
Motivation: Personalized medicine based on molecular aspects of diseases, such as gene expression profiling, has become increasingly popular. However, one faces multiple challenges when analyzing clinical gene expression data; most of the well-known theoretical issues such as high dimension of feature spaces versus few examples, noise and missing data apply. Special care is needed when designing classification procedures that support personalized diagnosis and choice of treatment. Here, we particularly focus on classification of interferon-β (IFNβ) treatment response in Multiple Sclerosis (MS) patients which has attracted substantial attention in the recent past. Half of the patients remain unaffected by IFNβ treatment, which is still the standard. For them the treatment should be timely ceased to mitigate the side effects.
Results: We propose constrained estimation of mixtures of hidden Markov models as a methodology to classify patient response to IFNβ treatment. The advantages of our approach are that it takes the temporal nature of the data into account and its robustness with respect to noise, missing data and mislabeled samples. Moreover, mixture estimation enables to explore the presence of response sub-groups of patients on the transcriptional level. We clearly outperformed all prior approaches in terms of prediction accuracy, raising it, for the first time, &gt;90%. Additionally, we were able to identify potentially mislabeled samples and to sub-divide the good responders into two sub-groups that exhibited different transcriptional response programs. This is supported by recent findings on MS pathology and therefore may raise interesting clinical follow-up questions.
Availability: The method is implemented in the GQL framework and is available at http://www.ghmm.org/gql. Datasets are available at http://www.cin.ufpe.br/∼igcf/MSConst
Contact: igcf@cin.ufpe.br
Supplementary information: Supplementary data are available at Bioinformatics online.
Speeding up HMM algorithms for genetic linkage analysis via chain reductions of the state space
Authors: Geiger Dan , Meek Christopher , Wexler Ydo 
Published: May 2009

AbstractWe develop an hidden Markov model (HMM)-based algorithm for computing exact parametric and non-parametric linkage scores in larger pedigrees than was possible before. The algorithm is applicable whenever there are chains of persons in the pedigree with no genetic measurements and with unknown affection status. The algorithm is based on shrinking the state space of the HMM considerably using such chains. In a two g-degree cousins pedigree the reduction drops the state space from being exponential in g to being linear in g. For a Finnish family in which two affected children suffer from a rare cold-inducing sweating syndrome, we were able to reduce the state space by more than five orders of magnitude from 250 to 232. In another pedigree of state-space size of 227, used for a study of pituitary adenoma, the state space reduced by a factor of 8.5 and consequently exact linkage scores can now be computed, rather than approximated.Contact: dang@cs.technion.ac.ilSupplementary information: Supplementary data are available at Bioinformatics online.
Multi-locus match probability in a finite population: a fundamental difference between the Moran and Wright–Fisher models
Authors: Bhaskar Anand , Song Yun S. 
Published: May 2009

Abstract
Motivation: A fundamental problem in population genetics, which being also of importance to forensic science, is to compute the match probability (MP) that two individuals randomly chosen from a population have identical alleles at a collection of loci. At present, 11–13 unlinked autosomal microsatellite loci are typed for forensic use. In a finite population, the genealogical relationships of individuals can create statistical non-independence of alleles at unlinked loci. However, the so-called product rule, which is used in courts in the USA, computes the MP for multiple unlinked loci by assuming statistical independence, multiplying the one-locus MPs at those loci. Analytically testing the accuracy of the product rule for more than five loci has hitherto remained an open problem.
Results: In this article, we adopt a flexible graphical framework to compute multi-locus MPs analytically. We consider two standard models of random mating, namely the Wright–Fisher (WF) and Moran models. We succeed in computing haplotypic MPs for up to 10 loci in the WF model, and up to 13 loci in the Moran model. For a finite population and a large number of loci, we show that the MPs predicted by the product rule are highly sensitive to mutation rates in the range of interest, while the true MPs computed using our graphical framework are not. Furthermore, we show that the WF and Moran models may produce drastically different MPs for a finite population, and that this difference grows with the number of loci and mutation rates. Although the two models converge to the same coalescent or diffusion limit, in which the population size approaches infinity, we demonstrate that, when multiple loci are considered, the rate of convergence in the Moran model is significantly slower than that in the WF model.
Availability: A C++ implementation of the algorithms discussed in this article is available at http://www.cs.berkeley.edu/∼yss/software.html.
Contact: yss@eecs.berkeley.edu
Genotype–phenotype associations: substitution models to detect evolutionary associations between phenotypic variables and genotypic evolutionary rate
Authors: O'Connor Timothy D. , Mundy Nicholas I. 
Published: May 2009

Abstract
Motivation: Mapping between genotype and phenotype is one of the primary goals of evolutionary genetics but one that has received little attention at the interspecies level. Recent developments in phylogenetics and statistical modelling have typically been used to examine molecular and phenotypic evolution separately. We have used this background to develop phylogenetic substitution models to test for associations between evolutionary rate of genotype and phenotype. We do this by creating hybrid rate matrices between genotype and phenotype.
Results: Simulation results show our models to be accurate in detecting genotype–phenotype associations and robust for various factors that typically affect maximum likelihood methods, such as number of taxa, level of relevant signal, proportion of sites affected and length of evolutionary divergence. Further, simulations show that our method is robust to homogeneity assumptions. We apply the models to datasets of male reproductive system genes in relation to mating systems of primates. We show that evolution of semenogelin II is significantly associated with mating systems whereas two negative control genes (cytochrome b and peptidase inhibitor 3) show no significant association. This provides the first hybrid substitution model of which we are aware to directly test the association between genotype and phenotype using a phylogenetic framework.
Availability: Perl and HYPHY scripts are available upon request from the authors.
Contact: to252@cam.ac.uk
Supplementary information: Supplementary data are available at Bioinformatics online.
An introduction to the proceedings and a synthesis of the 2008 ICES Symposium on the Ecosystem Approach with Fisheries Acoustics and Complementary Technologies (SEAFACTS)
Authors: Demer David A. , Kloser Rudy J. , MacLennan David N. , Ona Egil 
Published: May 2009

Abstract
Demer, D. A., Kloser, R. J., MacLennan, D. N., and Ona, E. 2009. An introduction to the proceedings and a synthesis of the 2008 ICES Symposium on the Ecosystem Approach with Fisheries Acoustics and Complementary Technologies (SEAFACTS). – ICES Journal of Marine Science, 66: 961–965.
A double-layer Boussinesq-type model for highly nonlinear and dispersive waves
Authors: Chazel F. , Benoit M. , Ern A. , Piperno S. 
Published: May 2009

We derive and analyse, in the framework of the mild-slope approximation, a new double-layer Boussinesq-type model that is linearly and nonlinearly accurate up to deep water. Assuming the flow to be irrotational, we formulate the problem in terms of the velocity potential, thereby lowering the number of unknowns. The model derivation combines two approaches, namely the method proposed by Agnonet al.(Agnonet al.1999J. Fluid Mech.399, 319–333) and enhanced by Madsenet al.(Madsenet al.2003Proc. R. Soc. Lond. A459, 1075–1104), which consists of constructing infinite-series Taylor solutions to the Laplace equation, to truncate them at a finite order and to use Padé approximants, and the double-layer approach of Lynett & Liu (Lynett & Liu 2004aProc. R. Soc. Lond. A460, 2637–2669), which allows lowering the order of derivatives. We formulate the model in terms of a static Dirichlet–Neumann operator translated from the free surface to the still-water level, and we derive an approximate inverse of this operator that can be built once and for all. The final model consists of only four equations both in one and two horizontal dimensions, and includes only second-order derivatives, which is a major improvement in comparison with so-called high-order Boussinesq models. A linear analysis of the model is performed, and its properties are optimized using a free parameter determining the position of the interface between the two layers. Excellent dispersion and shoaling properties are obtained, allowing the model to be applied up to the deep-water valuekh=10. Finally, numerical simulations are performed to quantify the nonlinear behaviour of the model, and the results exhibit a nonlinear range of validity reaching at leastkh=3π.
Refining the Definition of Plant Mitochondrial Presequences through Analysis of Sorting Signals, N-Terminal Modifications, and Cleavage Motifs
Authors: Huang Shaobai , Taylor Nicolas L. , Whelan James , Millar A. Harvey 
Published: May 2009

AbstractMitochondrial protein import is a complex multistep process from synthesis of proteins in the cytosol, recognition by receptors on the organelle surface, to translocation across one or both mitochondrial membranes and assembly after removal of the targeting signal, referred to as a presequence. In plants, import has to further discriminate between mitochondria and chloroplasts. In this study, we determined the precise cleavage sites in the presequences for Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa) mitochondrial proteins using mass spectrometry by comparing the precursor sequences with experimental evidence of the amino-terminal peptide from mature proteins. We validated this method by assessments of false-positive rates and comparisons with previous available data using Edman degradation. In total, the cleavable presequences of 62 proteins from Arabidopsis and 52 proteins from rice mitochondria were determined. None of these proteins contained amino-terminal acetylation, in contrast to recent findings for chloroplast stromal proteins. Furthermore, the classical matrix glutamate dehydrogenase was detected with intact and amino-terminal acetylated sequences, indicating that it is imported into mitochondria without a cleavable targeting signal. Arabidopsis and rice mitochondrial presequences had similar isoelectric points, hydrophobicity, and the predicted ability to form an amphiphilic α-helix at the amino-terminal region of the presequence, but variations in length, amino acid composition, and cleavage motifs for mitochondrial processing peptidase were observed. A combination of lower hydrophobicity and start point of the amino-terminal α-helix in mitochondrial presequences in both Arabidopsis and rice distinguished them (98%) from Arabidopsis chloroplast stroma transit peptides. Both Arabidopsis and rice mitochondrial cleavage sites could be grouped into three classes, with conserved −3R (class II) and −2R (class I) or without any conserved (class III) arginines. Class II was dominant in both Arabidopsis and rice (55%–58%), but in rice sequences there was much less frequently a phenylalanine (F) in the −1 position of the cleavage site than in Arabidopsis sequences. Our data also suggest a novel cleavage motif of (F/Y)↓(S/A) in plant class III sequences.
Primary dermal melanoma: A case report and molecular characterization
Authors: HIDA Yasutoshi , KUBO Yoshiaki , MIYAJIMA Osamu , ARASE Seiji 
Published: May 2009

ABSTRACTSwetter et al. proposed primary dermal melanoma (PDM) as a distinct entity based on an excellent prognosis. The histopathological features of PDM are extremely similar to those of metastatic melanoma or clear cell sarcoma (CCS). We describe a 38‐year‐old woman with a subcutaneous tumor in her left thigh. Physical and imaging examinations showed no evidence of metastatic melanoma. The lesion showed obvious strong expression of KIT by immunohistochemistry, but no EWS‐ATF1 fusion transcript specific for CCS was detected by reverse transcription polymerase chain reaction. In further analyses of KIT expression in other tumors, three of four primary melanomas (75%) and six of 12 metastatic melanomas (50%) were moderately or strongly positive, however, both the primary and metastatic lesions of CCS tested negative. We believe this to be a case of PDM, and emphasize the distinctiveness of PDM.
Clinical features of ileal pouch‐anal anastomosis in African American patients with underlying ulcerative colitis
Authors: MOORE L. , TANG L. , LOPEZ R. , SHEN B. 
Published: May 2009

SummaryBackground  The prevalence of inflammatory bowel disease in African Americans appears to be increasing. The data on differences in disease behavior and severity between the races have been conflicting.Aim  To evaluate the effect of race on outcome and natural history of patients with ileal pouch‐anal anastomosis.Methods  All African American patients with underlying ulcerative colitis and ileal pouch‐anal anastomosis who were seen in our subspecialty Pouchitis Clinic from 2002 to 2008 were included. The control group consisted of Caucasian patients with ulcerative colitis and ileal pouch‐anal anastomosis who were randomly selected from the same Pouch Registry at a ratio of 4:1. We compared pouch failure, Crohn’s disease of the pouch, and chronic pouchitis rates, as well as other 23 demographic and clinical variables between African American and Caucasian patients.Results  A total of 12 African American patients and 48 Caucasian patients were evaluated in this case‐control study. There were no significant differences in the frequency of pouch failure, Crohn’s disease of the pouch, or chronic pouchitis between the African American and Caucasian groups. However, African American patients were found to have a significantly shorter duration of inflammatory bowel disease (11.5 years vs. 17.0 years, P = 0.024) as well as significantly shorter duration of pouch (1.5 years vs. 4 years, P = 0.02). African Americans were also less likely to have pancolitis at the time of colectomy (83% vs. 100%, P = 0.037).Conclusions  While there were no significant differences in pouch outcomes between the races, African American patients appeared to have more left‐sided colitis at the time of colectomy, with a shorter duration of inflammatory bowel and ileal pouch. This finding suggests that the natural history of ulcerative colitis and disease course before and after restorative proctocolectomy may be different between these racial groups.
A new ‘total’ activin B enzyme‐linked immunosorbent assay (ELISA): development and validation for human samples
Authors: Ludlow Helen , Phillips David J. , Myers Michelle , McLachlan Robert I. , De Kretser David M. , Allan Carolyn A. , Anderson Richard A. , Groome Nigel P. , Hyvönen Marko , Colin Duncan W. , Muttukrishna Shanthi 
Published: May 2009

SummaryBackground and objective  There are currently no sensitive and specific assays for activin B that could be utilized to study human biological fluids. The aim of this project was to develop and validate a ‘total’ activin B ELISA for use with human biological fluids and establish concentrations of activin B in the circulation and fluids from the reproductive organs.Design  The new ELISA was validated and then used to measure activin B levels in the circulation of healthy participants, IVF patients, pregnant women and in ovarian follicular fluid and seminal plasma.Patients and measurements  Healthy adult subjects (n = 143), subjects from an IVF clinic (n = 27) and pregnancy groups (n = 29) were sampled.Results  The sensitivity of the assay was 0·019 ng/ml. Validation of the activin B ELISA showed good recovery (90·7 ± 9·8%) and linearity in biological fluid and cell culture media and low cross‐reactivity with related analytes (inhibin B = 0·077% and activin A = 0·0034%). There was a negative correlation between activin B concentration (r = −0·281, P < 0·011) and females with increasing age. Patients attending IVF clinics had significantly lower levels of activin B compared with gender‐matched control subjects. Ovarian follicular fluid and seminal plasma had 50–80 fold higher levels of activin B (mean = 5·35 and 3·66 ng/ml respectively) than sera (mean = 0·071 ng/ml).Conclusions  This fully validated ELISA for activin B offers a tremendous utility for measuring this protein in a variety of normal physiological processes and in various clinical pathologies.
Thyroid function and autoantibody status among women who spontaneously deliver under 35 weeks of gestation
Authors: Tierney Kelly , Delpachitra Pavitra , Grossmann Mathis , Onwude Joseph , Sikaris Ken , Wallace Euan M. , Hamilton Emma J. , Tong Stephen 
Published: May 2009

SummaryObjective  Recent studies report an association between maternal thyroid auto‐antibodies and preterm birth. None have made the important distinction between spontaneous and iatrogenic preterm birth. We investigated the association between spontaneous preterm birth before 35‐week gestation and both thyroid function and auto‐antibody status.Design  Retrospective nested case–control study, samples retrieved from a biobank of around 8000 samples.Patients  Forty‐six cases of spontaneous preterm birth <35‐weeks gestation compared with 124 cases who delivered at 40 weeks gestation, matched for maternal age and duration of serum storage. All resulted in a singleton liveborn.Measurements  First trimester serum levels of TSH, free T4, free T3, anti‐thyroid peroxidase (anti‐TPO) and anti‐thyroglobulin (anti‐Tg) antibodies.Results  Women who had a preterm birth delivered at a median gestational age of 33 (+1 day) weeks gestation (controls 40 + 3 weeks) and had significantly lower birthweight infants [mean (range) weight 1965 (581–3117) grams compared with controls 3526 (2685–4760) grams]. Median levels of anti‐thyroglobulin and anti‐TPO antibodies were similar in the two groups (Anti‐Tg: 3 IU/ml (Range 1–316) v 3 IU/ml (1–691); Anti‐TPO 8 IU/ml (3–73) v 9 IU/ml (3–499); P ≥ 0·18 for both comparisons, compared using three statistical models). In the preterm group, the median TSH level was 0·70 mIU/l (range 0·04–3·84), similar to controls (0·88 (0·01–2·87), P = 0·1). Free T3 and T4 levels were also similar in both groups.Conclusions  Thyroid function and thyroid autoantibody status among women who have a spontaneous preterm delivery before 35 weeks gestation are not different from women delivering at term.
Thermal acclimation of swimming performance in newt larvae: the influence of diel temperature fluctuations during embryogenesis
Authors: Měráková Eva , Gvoždík Lumír 
Published: May 2009

Summary1. Thermal acclimation is one of the basic strategies by which organisms cope with thermal heterogeneity of the environment. Under predictable variation in environmental temperatures, theory predicts that selection favours acclimation of thermal performance curves over fixed phenotypes.2. We examined the influence of diel fluctuations in developmental temperatures on the thermal sensitivity of the maximal swimming capacity in larvae of the alpine newt,Triturus alpestris.3. We incubated newt eggs under three thermal regimes with varying daily amplitudes (1, 5 and 9 °C) and similar means (17·6–17·9 °C), and accordingly we measured the swimming speed of hatched larvae at three experimental temperatures (12, 17 and 22 °C), which they would normally experience in their natural habitat.4. Embryonic development under low and middle temperature fluctuations produced larvae with similar swimming speeds across experimental temperatures. In contrast, the most fluctuating regime induced development of phenotypes, which at 12 °C swam faster than larvae developed under moderate diel fluctuations.5. Our results provide evidence that diel temperature fluctuations induce acclimation of thermal dependence of locomotor performance. In ectotherms experiencing diel cycles in environmental temperatures, this plastic response may act as an important pacemaker in the evolution of thermal sensitivity.