bluuebunny/crossref_metadata_2025_split huggingface dataset:
eSBMTools 1.0: enhanced native structure-based modeling tools
Authors: Lutz Benjamin , Sinner Claude , Heuermann Geertje , Verma Abhinav , Schug Alexander 
Published: September 2013

Abstract
Motivation: Molecular dynamics simulations provide detailed insights into the structure and function of biomolecular systems. Thus, they complement experimental measurements by giving access to experimentally inaccessible regimes. Among the different molecular dynamics techniques, native structure-based models (SBMs) are based on energy landscape theory and the principle of minimal frustration. Typically used in protein and RNA folding simulations, they coarse-grain the biomolecular system and/or simplify the Hamiltonian resulting in modest computational requirements while achieving high agreement with experimental data. eSBMTools streamlines running and evaluating SBM in a comprehensive package and offers high flexibility in adding experimental- or bioinformatics-derived restraints.
Results: We present a software package that allows setting up, modifying and evaluating SBM for both RNA and proteins. The implemented workflows include predicting protein complexes based on bioinformatics-derived inter-protein contact information, a standardized setup of protein folding simulations based on the common PDB format, calculating reaction coordinates and evaluating the simulation by free-energy calculations with weighted histogram analysis method or by phi-values. The modules interface with the molecular dynamics simulation program GROMACS. The package is open source and written in architecture-independent Python2.
Availability: http://sourceforge.net/projects/esbmtools/
Contact: alexander.schug@kit.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Accounting for epistatic interactions improves the functional analysis of protein structures
Authors: Wilkins Angela D. , Venner Eric , Marciano David C. , Erdin Serkan , Atri Benu , Lua Rhonald C. , Lichtarge Olivier 
Published: September 2013

Abstract
Motivation: The constraints under which sequence, structure and function coevolve are not fully understood. Bringing this mutual relationship to light can reveal the molecular basis of binding, catalysis and allostery, thereby identifying function and rationally guiding protein redesign. Underlying these relationships are the epistatic interactions that occur when the consequences of a mutation to a protein are determined by the genetic background in which it occurs. Based on prior data, we hypothesize that epistatic forces operate most strongly between residues nearby in the structure, resulting in smooth evolutionary importance across the structure.
Methods and Results: We find that when residue scores of evolutionary importance are distributed smoothly between nearby residues, functional site prediction accuracy improves. Accordingly, we designed a novel measure of evolutionary importance that focuses on the interaction between pairs of structurally neighboring residues. This measure that we term pair-interaction Evolutionary Trace yields greater functional site overlap and better structure-based proteome-wide functional predictions.
Conclusions: Our data show that the structural smoothness of evolutionary importance is a fundamental feature of the coevolution of sequence, structure and function. Mutations operate on individual residues, but selective pressure depends in part on the extent to which a mutation perturbs interactions with neighboring residues. In practice, this principle led us to redefine the importance of a residue in terms of the importance of its epistatic interactions with neighbors, yielding better annotation of functional residues, motivating experimental validation of a novel functional site in LexA and refining protein function prediction.
Contact: lichtarge@bcm.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Precise inference of copy number alterations in tumor samples from SNP arrays
Authors: Chen Gary K. , Chang Xiao , Curtis Christina , Wang Kai 
Published: September 2013

Abstract
Motivation: The accurate detection of copy number alterations (CNAs) in human genomes is important for understanding susceptibility to cancer and mechanisms of tumor progression. CNA detection in tumors from single nucleotide polymorphism (SNP) genotyping arrays is a challenging problem due to phenomena such as aneuploidy, stromal contamination, genomic waves and intra-tumor heterogeneity, issues that leading methods do not optimally address.
Results: Here we introduce methods and software (PennCNV-tumor) for fast and accurate CNA detection using signal intensity data from SNP genotyping arrays. We estimate stromal contamination by applying a maximum likelihood approach over multiple discrete genomic intervals. By conditioning on signal intensity across the genome, our method accounts for both aneuploidy and genomic waves. Finally, our method uses a hidden Markov model to integrate multiple sources of information, including total and allele-specific signal intensity at each SNP, as well as physical maps to make posterior inferences of CNAs. Using real data from cancer cell-lines and patient tumors, we demonstrate substantial improvements in accuracy and computational efficiency compared with existing methods.
Availability: Source code, documentation and example datasets are freely available at http://sourceforge.net/projects/penncnv-2.
Contact: gary.k.chen@usc.edu or kaichop@gmail.com
Supplementary information: Supplementary data are available at Bioinformatics online.
HMCan: a method for detecting chromatin modifications in cancer samples using ChIP-seq data
Authors: Ashoor Haitham , Hérault Aurélie , Kamoun Aurélie , Radvanyi François , Bajic Vladimir B. , Barillot Emmanuel , Boeva Valentina 
Published: September 2013

Abstract
Motivation: Cancer cells are often characterized by epigenetic changes, which include aberrant histone modifications. In particular, local or regional epigenetic silencing is a common mechanism in cancer for silencing expression of tumor suppressor genes. Though several tools have been created to enable detection of histone marks in ChIP-seq data from normal samples, it is unclear whether these tools can be efficiently applied to ChIP-seq data generated from cancer samples. Indeed, cancer genomes are often characterized by frequent copy number alterations: gains and losses of large regions of chromosomal material. Copy number alterations may create a substantial statistical bias in the evaluation of histone mark signal enrichment and result in underdetection of the signal in the regions of loss and overdetection of the signal in the regions of gain.
Results: We present HMCan (Histone modifications in cancer), a tool specially designed to analyze histone modification ChIP-seq data produced from cancer genomes. HMCan corrects for the GC-content and copy number bias and then applies Hidden Markov Models to detect the signal from the corrected data. On simulated data, HMCan outperformed several commonly used tools developed to analyze histone modification data produced from genomes without copy number alterations. HMCan also showed superior results on a ChIP-seq dataset generated for the repressive histone mark H3K27me3 in a bladder cancer cell line. HMCan predictions matched well with experimental data (qPCR validated regions) and included, for example, the previously detected H3K27me3 mark in the promoter of the DLEC1 gene, missed by other tools we tested.
Availability: Source code and binaries can be downloaded at http://www.cbrc.kaust.edu.sa/hmcan/, implemented in C++.
Contact: haitham.ashoor@kaust.edu.sa
Supplementary information: Supplementary data are available at Bioinformatics online.
BioPig: a Hadoop-based analytic toolkit for large-scale sequence data
Authors: Nordberg Henrik , Bhatia Karan , Wang Kai , Wang Zhong 
Published: September 2013

Abstract
Motivation: The recent revolution in sequencing technologies has led to an exponential growth of sequence data. As a result, most of the current bioinformatics tools become obsolete as they fail to scale with data. To tackle this ‘data deluge’, here we introduce the BioPig sequence analysis toolkit as one of the solutions that scale to data and computation.
Results: We built BioPig on the Apache’s Hadoop MapReduce system and the Pig data flow language. Compared with traditional serial and MPI-based algorithms, BioPig has three major advantages: first, BioPig’s programmability greatly reduces development time for parallel bioinformatics applications; second, testing BioPig with up to 500 Gb sequences demonstrates that it scales automatically with size of data; and finally, BioPig can be ported without modification on many Hadoop infrastructures, as tested with Magellan system at National Energy Research Scientific Computing Center and the Amazon Elastic Compute Cloud. In summary, BioPig represents a novel program framework with the potential to greatly accelerate data-intensive bioinformatics analysis.
Availability and implementation: BioPig is released as open-source software under the BSD license at https://sites.google.com/a/lbl.gov/biopig/
Contact: ZhongWang@lbl.gov
DEC-205-mediated antigen targeting to steady-state dendritic cells induces deletion of diabetogenic CD8+ T cells independently of PD-1 and PD-L1
Authors: Mukherjee Gayatri , Geliebter Ari , Babad Jeffrey , Santamaria Pere , Serreze David V. , Freeman Gordon J. , Tarbell Kristin V. , Sharpe Arlene , DiLorenzo Teresa P. 
Published: September 2013

AbstractCD8+ T cells specific for islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) have been implicated in type 1 diabetes in both humans and non-obese diabetic (NOD) mice, in which T cells specific for IGRP206–214 are highly prevalent. We sought to manipulate these pathogenic T cells by exploiting the ability of steady-state dendritic cells (DCs) to present antigens in a tolerogenic manner. The endocytic receptor DEC-205 was utilized to deliver an IGRP206–214 mimotope to DCs in NOD mice, and the impact of this delivery on a polyclonal population of endogenous islet-reactive cognate T cells was determined. Assessment of islet-infiltrating CD8+ T cells showed a decrease in the percentage, and the absolute number, of endogenous IGRP206–214-specific T cells when the mimotope was delivered to DCs, compared with delivery of a specificity control. Employing an adoptive transfer system, deletion of CD8+ T cells as a result of DEC-205-mediated antigen targeting was found to occur independently of programmed death-1 (PD-1) and its ligand (PD-L1), both often implicated in the regulation of peripheral T-cell tolerance. Given its promise for the manipulation of self-reactive polyclonal T cells demonstrated here, the distinctive characteristics of this antigen delivery system will be important to appreciate as its potential as an intervention for autoimmune diseases continues to be investigated.
Health promotion and health care for school-age children and young people
Authors: Hall David M.
              B. , Elliman David 
Published: September 2013

Abstract
Chapter 5 reviews the changing needs of health care for school-age children, a needs-based approach, the views of children and young people about their concerns and the service they want, starting school—preparation for school and reception into school, special medical needs of children in school, emotional and behavioural problems, bullying, the need for confidential advice and support, the National Healthy Schools Standard and other Government initiatives—health promotion in school, profiles, and prevention of unwanted pregnancy and support for young mothers.
Physical examination
Authors: Hall David M.
              B. , Elliman David 
Published: September 2013

Abstract
Chapter 7 covers the neonatal and 6–8 week examinations, the school entrant examination, and screening by physical examination for developmental dysplasia of the hip (DDH) (previously known as congenital dislocation of the hip), heart disease including hypertrophic cardiomyopathy (HCM), hypertension, asthma, and undescended testes and other genital abnormalities.
The universal programme
Authors: Hall David M.
              B. , Elliman David 
Published: September 2013

Abstract
Chapter 18 summarizes the justification for providing a universal preventive child health service for families, children, and young people, sets out the general principles which underpin such a programme, summarizes the objectives of a universal programme, describes the core programme of pre-school care and the need for a programme for school-age children and young people, and emphasizes the importance of adequate community resources to deal with problems detected and to undertake effective prevention and health promotion strategies.
Ethics in paediatric research: principles and processes
Authors: Winter Edward
                M. , Cobb Mark 
Published: September 2013

Abstract
Chapter 1 outlines principles that underpin ethics approval and processes by which ethics approval can be sought and granted. While the former is important, emphasis will be placed on the latter because it is the practicalities that are particularly challenging, and a key intention of this chapter is to help researchers chart their way through the tortuous and convoluted pathways that characterize research governance. Out of necessity, the approach will tend to take a United Kingdom-centric perspective, but much of current practice is determined by European Union legislation, and similar procedures are in place elsewhere in the world.
Interpreting exercise performance data in relation to body size
Authors: Welsman Joanne
                R. , Armstrong Neil 
Published: September 2013

Abstract
The appropriate normalization of exercise performance data for differences in body size underpins the clarification of growth and maturational influences on physiological function. Therefore, scaling is an issue of fundamental importance for all paediatric exercise scientists. The selection and application of a scaling method appropriate for the data and research question being addressed is at least as important as ensuring that the methodology used to collect the data is valid, reliable, and appropriate for use with young people. Several scaling methods are available and some methods can be applied in different ways. Unfortunately, taken as a whole, the extant literature presents a confusing picture as to which of these techniques is preferable, how they should be applied, and the meaning of the results obtained. The aim of this chapter is to clarify these issues through a description of the techniques available for analysing both cross-sectional and longitudinal data sets, highlighting their statistical and theoretical derivations.
Maximal intensity exercise
Authors: Armstrong Neil , Welsman Joanne
                R. , Williams Craig
                A. 
Published: September 2013

Abstract
Chapter 5 discusses maximal intensity exercise, which is often associated with maximal or peak oxygen uptake (VO2·). However, this convention ignores the fact that, for short periods of time, anaerobic provision of adenosine triphosphate (ATP) can support exercise of much greater intensity than that at peak VO2· Th erefore, for the purpose of this chapter, maximal intensity exercise is defi ned as that which is performed ‘all-out’ and is sustained by an anaerobic ATP yield which exceeds that of oxidative metabolism.
Cardiovascular function
Authors: Warburton Darren
                E.R. , Nettlefold Lindsay , McGuire K.
                Ashlee , Bredin Shannon
                S.D. 
Published: September 2013

Abstract
The physiological adaptations to exercise training have been evaluated extensively in children and youth. In particular, considerable research has examined the changes in cardiovascular function that occur with aerobic exercise training. Various indicators of cardiovascular function have been assessed at rest and during exercise. Many of these measures have important implications from performance and health-related perspectives. Owing to the importance of oxygen (O2) transport for human performance and health, this chapter reviews comprehensively the varied non-invasive and invasive methods of assessing cardiac function including an in-depth evaluation of the limitations and strengths of each methodology. Specific reference is given to the applicability and ease of usage of each technology with young people. This chapter also deals extensively with the evaluation of cardiovascular regulation and vascular function owing to their role in optimal exercise performance and health.
Muscle strength
Authors: De Ste Croix Mark B.
                A. 
Published: September 2013

Abstract
Despite a relatively limited understanding of the factors associated with strength development, advances in equipment, and increased understanding of growth and maturation issues, have provided new insights into paediatric muscle strength development. Strength testing of children is performed routinely by researchers to monitor the determinants and development of strength throughout childhood, and also by physiotherapists to assess the degree of muscle disability and to diagnose the rate of recovery. It is important for strength test administrators to be equipped with knowledge of the normal age and sex-associated variations in strength and the factors attributable to that variation. Over time, the use of differing techniques to adjust for body size has changed our perspective of the historical concept of the age- and sex-associated differences in muscle strength. Likewise, the development of more sophisticated techniques to determine muscle size and body composition has allowed researchers to explore the factors associated with the development of strength during growth with a greater degree of validity.
Maximal intensity exercise
Authors: Williams Craig
                A. 
Published: September 2013

Abstract
Despite a surge of interest over the past 10 years in young people’s maximal intensity exercise, the growth and maturation of anaerobic performance is still poorly understood. This observation is interesting for a number of reasons. First, during the prepubertal years, children’s physical activity patterns are characterized by short duration but high intensity bouts of effort.5 Second, investigators are limited by the range of available methodologies, most of which are assessing external but indirect mechanical indices of maximal intensity so as to deduce metabolic changes. Third, there are few data available from females. Finally, due to the importance of maximal intensity efforts during team sports and the increasing emphasis on organized youth sport programmes, the differentiation between growth and maturation and training adaptations of maximal intensity performance need to be addressed. As a consequence of these four observations, important reliability and validity issues need to be resolved prior to paediatric exercise scientists determining which key factors influence maximal intensity exercise during childhood and adolescence. This chapter will therefore focus on the variables that have been most commonly measured and review the explanatory factors related to maximal intensity exercise during growth and maturation.
Aerobic fitness
Authors: Armstrong Neil , McManus Alison
                M. , Welsman Joanne
                R. 
Published: September 2013

Abstract
Peak V·O2 limits the child’s capacity to perform aerobic exercise but it does not describe fully all aspects of aerobic fitness. Exercise of the intensity and duration required to elicit peak V·O2 is rarely experienced by many young people.17,18 The vast majority ofhabitual physical activity is submaximal and of short duration and, under these circumstances, it is the transient kinetics of V·O2 which reflect the integrated response of the oxygen delivery system and the metabolic requirements of the exercising muscle.19–21 Furthermore, peak V·O2 is neither the best measure of a child’s ability to sustain submaximal aerobic exercise nor the most sensitive means to detect improvements in aerobic fitness after a training programme. Despite its origins in anaerobic metabolism, blood lactate accumulation is a valuable indicator of aerobic fitness and it can be used to monitor improvements in muscle oxidative capacity with exercise training in the absence of changes in peak V·O2.16,22 However, as V·O2 kinetics is comprehensively reviewed in Chapter 22 and blood lactate accumulation during exercise is analysed in Chapter 8, we will focus herein on aerobic fitness as described by peak V·O2.
Locomotor economy
Authors: Morgan Don
                W. 
Published: September 2013

Abstract
Chapter 21 presents and synthesizes research findings related to various aspects of locomotor economy during the childhood and adolescent years. Because the majority of research has been conducted on walking and running, the material presented in this chapter will focus exclusively on these modes of gait. It concludes by proposing future research directions to guide sport scientists, coaches, and clinicians in their quest to understand the factors responsible for efficient locomotion in children, improve the athletic performance of youngsters, and enhance the functional mobility and quality of life of physically challenged youth.
Temperature regulation
Authors: Falk Bareket , Dotan Raffy 
Published: September 2013

Abstract
This chapter outlines the physical and physiological changes that occur during growth and maturation and the possible effects these changes can have on the nature and effectiveness of thermoregulation. The physiological responses to heat stress are discussed in terms of metabolic, circulatory, hormonal, and sweating responses, changes in body temperature, and in terms of heat tolerance. Also discussed is hydration status, which can affect thermoregulatory effectiveness in the heat. The physiological response to cold stress is considered in terms of the metabolic and circulatory responses and their possible influence on the effectiveness of thermoregulation. The discussion does not outline the thermoregulatory response per se, but rather emphasizes the differences in that response between children and adults. Finally, child–adult differences in the acclimatization- and training-induced adaptations to thermal stress are discussed.
Exercise, physical activity, and cystic fibrosis
Authors: Kriemler Susi 
Published: September 2013

Abstract
Cystic fibrosis (CF) is the most common genetic autosomal recessive disease of the Caucasian race, generally leading to death in early adulthood.1 The frequency of the gene carrier (heterozygote) is 1:20–25 in Caucasian populations, 1:2000 in African-Americans, and practically non-existent in Asian populations. The disease occurs in about 1 in every 2500 life births of the white population. Mean survival has risen from 8.4 years in 1969 to 32 years in 2000 due to improvements in treatment. The genetic defect causes a pathological electrolyte transport through the cell membranes by a defective chloride channel membrane transport protein [cystic fibrosis transmembrane conductance regulator (CFTR)]. With respect to the function, this affects mainly the exocrine glands of secretory cells, sinuses, lungs, pancreas, liver, and the reproductive tract of the human body leading to a highly viscous, water-depleted secretion. The secretion cannot leave the glands and in consequence causes local inflammation and destruction of various organs. The main symptoms include chronic inflammatory pulmonary disease with a progressive loss of lung function, exocrine and sometimes endocrine pancreas insufficiency, and an excessive salt loss through the sweat glands.1 A summary of the signs and symptoms of CF will be given with a special emphasis on the effect of exercise performance and capacity.