bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pidgins and Creoles
Authors: Baptista Marlyse 
Published: February 2017

Abstract
This chapter offers an overview of the controversies surrounding the study of creole syntax while evaluating representative studies. This overview includes proposals that cast creoles as a “type” of languages, proposals that view creoles as interlanguages and resulting from second language acquisition, and proposals that consider them as hybrid grammars yielding innovative feature recombinations due to language contact. It also discusses the benefits of the Atlas of Pidgin and Creole Structures, as it lays out a promising new direction in the investigation of pidgins and creoles by offering systematic comparisons of a large sample of creoles and their source languages. This collaborative Atlas provides broad empirical coverage, testing the hypotheses reflected by the various positions and schools of thought discussed in this chapter while unveiling the rich diversity of creole syntactic features.
The Ethics of War
Authors: Frowe Helen , Lazar Seth 
Published: February 2017

Abstract
War is not the only or even the major cause of human suffering. But it is the cause for which we are most often most directly responsible. Our voluntary choices result in huge increases in mortality, massive refugee crises, and the dislocation of whole generations. So while there are other equally pressing problems facing humanity, none of them raises as pointed moral questions as those to do with whether and when we may take our polities to war and how we must fight if we do so. This Handbook offers a guide to thinking through the morality of war, from the perspective of contemporary analytical just war theory. This introduction explains the methodological and substantive choices made in designing the volume, then summarizes the key insights of the chapters to follow.
Is Pelvic-Floor Muscle Training a Physical Therapy or a Behavioral Therapy? A Call to Name and Report the Physical, Cognitive, and Behavioral Elements
Authors: Frawley Helena C. , Dean Sarah G. , Slade Susan C. , Hay-Smith E. Jean C. 
Published: February 2017

Abstract
This perspective article explores whether pelvic-floor muscle training (PFMT) for the management of female urinary incontinence and prolapse is a physical therapy or a behavioral therapy. The primary aim is to demonstrate that it is both. A secondary aim is to show that the plethora of terms used for PFMT is potentially confusing and that current terminology inadequately represents the full intent, content, and delivery of this complex intervention. While physical therapists may be familiar with exercise terms, the details are often incompletely reported; furthermore, physical therapists are less familiar with the terminology used in accurately representing cognitive and behavioral therapy interventions, which results in these elements being even less well reported. Thus, an additional aim is to provide greater clarity in the terminology used in the reporting of PFMT interventions, specifically, descriptions of the exercise and behavioral elements. First, PFMT is described as a physical therapy and as an exercise therapy informed predominantly by the discipline of physical therapy. However, effective implementation requires use of the cognitive and behavioral perspectives of the discipline of psychology. Second, the theoretical underpinning of the psychology-informed elements of PFMT is summarized. Third, to address some identified limitations and confusion in current terminology and reporting, recommendations for ways in which physical therapists can incorporate the psychology-informed elements of PFMT alongside the more familiar exercise therapy–informed elements are made. Fourth, an example of how both elements can be described and reported in a PFMT intervention is provided. In summary, this perspective explores the underlying concepts of PFMT to demonstrate that it is both a physical intervention and a behavioral intervention and that it can and should be described as such, and an example of the integration of these elements into clinical practice is provided.
Gross Motor Trajectories During the First Year of Life for Preterm Infants With Very Low Birth Weight
Authors: Su Yu-Han , Jeng Suh-Fang , Hsieh Wu-Shiun , Tu Yu-Kang , Wu Yen-Tzu , Chen Li-Chiou 
Published: February 2017

Abstract

Background
Early identification of motor dysfunction in preterm infants with very low birth weight (VLBW) is important in order to provide early intervention.

Objective
This study was to examine the motor trajectories of preterm infants with VLBW during their first year of life and to investigate the predictive ability and influencing factors of the trajectories.

Design and Methods
A total of 342 preterm infants with VLBW were prospectively assessed for motor development by the Alberta Infant Motor Scales at 4, 6, 9, and 12 months and for developmental outcomes using the Bayley Scales of Infant and Toddler Development, second edition, at 24 months. Perinatal and socio-environmental factors were collected at baseline. Growth mixture modeling was used to explore the patterns of infants’ motor trajectories during their first year of life. Logistic regression analyses were applied to examine the influencing factors associated with motor trajectories and their predictability of 24-month developmental outcomes.

Results
Preterm infants with VLBW showed 3 distinct motor trajectories: stably normal (55%), deteriorating (32%), and persistently delayed (13%). Furthermore, the motor trajectories were predictive of 24-month cognitive and motor outcomes. Perinatal factors including lower birth weight, male gender, moderate to severe bronchopulmonary dysplasia, stage III to IV retinopathy of prematurity, and major brain damage were associated with a risk of deteriorating and persistently delayed trajectories (all P &lt; .05). Socio-environmental factors had no association with motor trajectories.

Limitations
The small sample size of the infants with a persistently delayed trajectory may have limited the assessment of some influencing factors.

Conclusion
The identified early motor trajectories, predictive values, and influencing factors provide insightful implications for early detection and prevention of motor -disorders in preterm infants with VLBW.
Predicting susceptibility to tuberculosis based on gene expression profiling in dendritic cells
Authors: Blischak John D. , Tailleux Ludovic , Myrthil Marsha , Charlois Cécile , Bergot Emmanuel , Dinh Aurélien , Morizot Gloria , Chény Olivia , Von Platen Cassandre , Herrmann Jean-Louis , Brosch Roland , Barreiro Luis B. , Gilad Yoav 
Published: February 2017

ABSTRACTTuberculosis (TB) is a deadly infectious disease, which kills millions of people every year. The causative pathogen,Mycobac-terium tuberculosis(MTB), is estimated to have infected up to a third of the world’s population; however, only approximately 10% of infected healthy individuals progress to active TB. Despite evidence for heritability, it is not currently possible to predict who may develop TB. To explore approaches to classify susceptibility to TB, we infected with MTB dendritic cells (DCs) from putatively resistant individuals diagnosed with latent TB, and from susceptible individuals that had recovered from active TB. We measured gene expression levels in infected and non-infected cells and found hundreds of differentially expressed genes between susceptible and resistant individuals in the non-infected cells. We further found that genetic polymorphisms nearby the differentially expressed genes between susceptible and resistant individuals are more likely to be associated with TB susceptibility in published GWAS data. Lastly, we trained a classifier based on the gene expression levels in the non-infected cells, and demonstrated decent performance on our data and an independent data set. Overall, our promising results from this small study suggest that training a classifier on a larger cohort may enable us to accurately predict TB susceptibility.
Interactions between genetic variation and cellular environment in skeletal muscle gene expression
Authors: Taylor D. Leland , Knowles David A. , Scott Laura J. , Ramirez Andrea H. , Paolo Casale Franceso , Wolford Brooke N. , Guan Li , Varshney Arushi , Oliveira Albanus Ricardo , Parker Stephen C.J. , Narisu Narisu , Chines Peter S. , Erdos Michael R. , Welch Ryan P. , Kinnunen Leena , Saramies Jouko , Sundvall Jouko , Lakka Timo A. , Laakso Markku , Tuomilehto Jaakko , Koistinen Heikki A. , Stegle Oliver , Boehnke Michael , Birney Ewan , Collins Francis S. 
Published: February 2017

AbstractFrom whole organisms to individual cells, responses to environmental conditions are influenced by genetic makeup, where the effect of genetic variation on a trait depends on the environmental context. RNA-sequencing quantifies gene expression as a molecular trait, and is capable of capturing both genetic and environmental effects. In this study, we explore opportunities of using allele-specific expression (ASE) to discovercisacting genotype-environment interactions (GxE) - genetic effects on gene expression that depend on an environmental condition. Treating 17 common, clinical traits as approximations of the cellular environment of 267 skeletal muscle biopsies, we identify 10 candidate interaction quantitative trait loci (iQTLs) across 6 traits (12 unique gene-environment trait pairs; 10% FDR per trait) including sex, systolic blood pressure, and low-density lipoprotein cholesterol. Although using ASE is in principle a promising approach to detect GxE effects, replication of such signals can be challenging as validation requires harmonization of environmental traits across cohorts and a sufficient sampling of heterozygotes for a transcribed SNP. Comprehensive discovery and replication will require large human transcriptome datasets, or the integration of multiple transcribed SNPs, coupled with standardized clinical phenotyping.
CAFE MOCHA:An Integrated Platform for Discovering Clinically Relevant Molecular Changes in Cancer; an Example of Distant Metastasis and Recurrence-linked Classifiers in Head and Neck Squamous Cell Carcinoma
Authors: Krishnan Neeraja M , Mohanraj I , Hariharan Janani , Panda Binay 
Published: February 2017

AbstractBackgroundCAFE MOCHA(Clinical Association of Functionally Established MOlecular CHAnges) is an integrated GUI-driven computational and statistical framework to discover molecular signatures linked to a specific clinical attribute in a cancer type. We testedCAFE MOCHAin head and neck squamous cell carcinoma (HNSCC) for discovering a signature linked to distant metastasis and recurrence (MR) in 517 tumors from TCGA and validated the signature in 18 tumors from an independent cohort.MethodsThe platform integrates mutations and indels, gene expression, DNA methylation and copy number variations to discover a classifier first, predict an incoming tumour for the same by pulling defined class variables into a single framework that incorporates a coordinate geometry-based algorithm, called Complete Specificity Margin Based Clustering (CSMBC) with 100% specificity.CAFE MOCHAclassifies an incoming tumour sample using either a matched normal or a built-in database of normal tissues. The application is packed and deployed using theinstall4jmulti-platform installer.ResultsWe testedCAFE MOCHAto discover a signature for distant metastasis and recurrence in HNSCC. The signature MR44 in HNSCC yielded 80% sensitivity and 100% specificity in the discovery stage and 100% sensitivity and 100% specificity in the validation stage.ConclusionsCAFE MOCHAis a cancer type- and clinical attribute-agnostic computational and statistical framework to discover integrated molecular signature for a specific clinical attribute.CAFE MOCHAis available in GitHub (https://github.com/binaypanda/CAFEMOCHA).
Microvessel Chaste: An Open Library for Spatial Modelling of Vascularized Tissues
Authors: Grogan J.A. , Connor A.J. , Markelc B. , Muschel R.J. , Maini P.K. , Byrne H.M. , Pitt-Francis J.M. 
Published: February 2017

AbstractSpatial models of vascularized tissues are widely used in computational physiology, to study for example, tumour growth, angiogenesis, osteogenesis, coronary perfusion and oxygen delivery. Composition of such models is time-consuming, with many researchers writing custom software for this purpose. Recent advances in imaging have produced detailed three-dimensional (3D) datasets of vascularized tissues at the scale of individual cells. To fully exploit such data there is an increasing need for software that allows user-friendly composition of efficient, 3D models of vascularized tissue growth, and comparison of predictions with in vivo or in vitro experiments and other models. Microvessel Chaste is a new open-source library for building spatial models of vascularized tissue growth. It can be used to simulate vessel growth and adaptation in response to mechanical and chemical stimuli, intra- and extra-vascular transport of nutrient, growth factor and drugs, and cell proliferation in complex 3D geometries. The library provides a comprehensive Python interface to solvers implemented in C++, allowing user-friendly model composition, and integration with experimental data. Such integration is facilitated by interoperability with a growing collection of scientific Python software for image processing, statistical analysis, model annotation and visualization. The library is available under an open-source Berkeley Software Distribution (BSD) licence at https://jmsgrogan.github.io/MicrovesselChaste. This article links to two reproducible example problems, showing how the library can be used to model tumour growth and angiogenesis with realistic vessel networks.
Normalization of Mass Spectrometry Data (NOMAD)
Authors: Murie Carl , Sandri Brian , Griffin Timothy J. , Wendt Christine , Larsson Ola 
Published: February 2017

AbstractMotivationiTRAQ reagent-based mass spectrometry (MS) is a commonly used technology for identification and quantification of proteins in biological samples. Such studies are often performed over multiple MS runs, potentially resulting in introduction of MS run bias that could affect downstream analysis. iTRAQ MS data have therefore commonly been normalized using a reference sample which is included in each MS run. We show, however, that such normalization does not efficiently remove systematic MS run bias. A linear model approach was previously proposed to improve on the reference normalization approach but does not computationally scale to larger data. Here we describe the NOMAD (normalization of mass spectrometry data) R package which implements a computationally efficient ANOVA normalization approach with protein assembly functionality.ResultsNOMAD provides the same advantages as the linear regression solution but is more computationally efficient which allows superior scaling to larger sample sizes. Moreover, NOMAD efficiently removes bias which allows for valid across MS run comparisons.AvailabilityThe NOMAD Bioconductor package:www.bioconductor.orgContactola.larsson@ki.se;carl.murie@ki.se
VREX: An Open-Source Toolbox for Creating 3D Virtual Reality Experiments
Authors: Vasser Madis , Kängsepp Markus , Magomedkerimov Murad , Kilvits Kälver , Stafinjak Vladislav , Kivisik Taavi , Vicente Raul , Aru Jaan 
Published: February 2017

AbstractBackgroundWe present VREX, a free open-source Unity toolbox for virtual reality research in the fields of experimental psychology and neuroscience.ResultsDifferent study protocols about perception, attention, cognition and memory can be constructed using the toolbox. VREX provides a procedural generation of (interconnected) rooms that can be automatically furnished with a click of a button. VREX includes a menu system for creating and storing experiments with different stages. Researchers can combine different rooms and environments to perform end-to-end experiments including different testing situations and data collection. For fine-tuned control VREX also comes with an editor where all the objects in the virtual room can be manually placed and adjusted in the 3D world.ConclusionsVREX simplifies the generation and setup of complicated VR scenes and experiments for researchers. VREX can be downloaded and easily installed fromvrex.mozello.com
Structure of a AAA+ unfoldase in the process of unfolding substrate
Authors: Ripstein Zev. A , Huang Rui , Augustyniak Rafal , Kay Lewis E. , Rubinstein John L. 
Published: February 2017

AbstractAAA+ unfoldases are thought to unfold substrate through the central pore of their hexameric structures, but how this process occurs is not known. VAT, theThermoplasma acidophilumhomologue of eukaryotic CDC48/p97, works in conjunction with the proteasome to degrade misfolded or damaged proteins. We show that in the presence of ATP, VAT with its regulatory N-terminal domains removed unfolds other VAT complexes as substrate. We captured images of this transient process by electron cryomicroscopy (cryo-EM) to reveal the structure of the substrate-bound intermediate. Substrate binding breaks the six-fold symmetry of the complex, allowing five of the six VAT subunits to constrict into a tight helix that grips an ~80 Å stretch of unfolded protein. The structure suggests a processive hand-over-hand unfolding mechanism, where each VAT subunit releases the substrate in turn before re-engaging further along the target protein, thereby unfolding it.
The mammalian kinetochore independently regulates its passive and active force-generating interfaces with microtubules
Authors: Long Alexandra F. , Udy Dylan B. , Dumont Sophie 
Published: February 2017

SummaryThe kinetochore links chromosomes to dynamic spindle microtubules and drives both chromosome congression and segregation. To do so, the kinetochore must hold on to depolymerizing and polymerizing microtubules. At metaphase, one sister kinetochore couples to depolymerizing microtubules, pulling its sister along polymerizing microtubules [1,2]. Distinct kinetochore-microtubule interfaces mediate these behaviors: active interfaces transduce microtubule depolymerization into mechanical work, and passive interfaces generate friction as the kinetochore slides along microtubules [3,4]. We do not know the physical and molecular nature [5–7] of these interfaces, or how they are regulated to support diverse mitotic functions in mammalian cells. To address this question, we focus on the mechanical role of the essential load-bearing protein Hec1 [8–11]. Hec1’s affinity for microtubules is regulated by Aurora B phosphorylation on its N-terminal tail [12–15], but its role at the passive and active interfaces remains unclear. Here, we use laser ablation to trigger cellular pulling on mutant kinetochores and decouple sistersin vivo, and thereby separately probe Hec1’s role as it moves on polymerizing versus depolymerizing microtubules. We show that Hec1 phosphorylation tunes passive friction along polymerizing microtubules, modulating both the magnitude and timescale of responses to force. In contrast, we find that Hec1 phosphorylation does not affect the kinetochore’s ability to grip depolymerizing microtubules, or switch to this active force-generating state. Together, the data suggest that different kinetochore interfaces engage with growing and shrinking microtubules, and that passive friction can be regulated without disrupting active force generation. Through this mechanism, the kinetochore can modulate its grip on microtubules as its functional needs change during mitosis, and yet retain its ability to couple to microtubules powering chromosome movement.
Prediction of Molecular Mechanisms of Breast Cancer Metastasis
Authors: Siwo Geoffrey H. , Stolovitzky Gustavo A. , Assefa Solomon 
Published: February 2017

AbstractMetastasis -the spread of cancer to other parts of the body- causes 90% of cancer deaths, underlies major health complications in cancer patients and renders most cancers incurable. Unfortunately, the molecular mechanisms underlying the process are poorly understood and therapeutics to block it remain elusive. Here, we present a computational technique for scanning genome-scale regulatory networks for potential genes associated with metastasis. First, we demonstrate that in the breast cancer cell line MCF7, the commonly dysregulated cancer biomarkers TP53, ERBB2, ESR1 and PGR are closely connected to known metastasis genes with a significant proportion being 2nddegree neighbors of a given biomarker. Next, we identify genes whose 2nddegree neighbors are connected in a similar manner to these biomarkers. Consequently, these are referred to as metastasis associated genes or MAGs. We identify 190 genes that are TP53-MAGs, 22 ERBB2-MAGs, 240 ESR1-MAGs and 84 PGR-MAGs (FDR adjustedP<0.001). Analysis of the MAGs reveals statistically significant enrichment with biological functions previously associated with metastasis including the extracellular matrix (ECM) receptor interaction, focal adhesion, cytokine-cytokine receptor interaction and chemokine signaling. The biological significance of MAGs is further supported by their enrichment with experimentally validated binding sites for transcription factors that regulate metastasis, for example BACH1- a master regulator of breast cancer metastasis to bone. The predicted MAGs are also clinically relevant as therapeutic targets for metastasis blocking agents. Specifically, genes that are perturbed by drugs and miRNAs that influence metastasis are enriched with MAGs. Furthermore, some MAGs are associated with patient survival and provide insights into the proclivity for breast cancer subtypes to preferentially spread to specific organs. The results of this study imply that aberrations in primary tumors may constrict metastasis trajectories. This could enable the prediction of organ specific metastases based on aberrations in the primary tumor and lay a foundation for future studies on individualized or personalized models of metastasis. The approach is potentially scalable across other cancers and has clinical implications.
Holotomography: refractive index as an intrinsic imaging contrast for 3-D label-free live cell imaging
Authors: Kim Doyeon , Lee SangYun , Lee Moosung , Oh JunTaek , Yang Su-A , Park YongKeun 
Published: February 2017

AbstractLive cell imaging provides essential information in the investigation of cell biology and related pathophysiology. Refractive index (RI) can serve as intrinsic optical imaging contrast for 3-D label-free and quantitative live cell imaging, and provide invaluable information to understand various dynamics of cells and tissues for the study of numerous fields. Recently significant advances have been made in imaging methods and analysis approaches utilizing RI, which are now being transferred to biological and medical research fields, providing novel approaches to investigate the pathophysiology of cells. To provide insight how RI can be used as an imaging contrast for imaging of biological specimens, here we provide the basic principle of RI-based imaging techniques and summarize recent progress on applications, ranging from microbiology, hematology, infectious diseases, hematology, and histopathology.