bluuebunny/crossref_metadata_2025_split huggingface dataset:
The HER2 inhibitor TAK165 Sensitizes Human Acute Myeloid Leukemia Cells to Retinoic Acid-Induced Myeloid Differentiation by activating MEK/ERK mediated RARα/STAT1 axis
Authors: Shao Xuejing , Liu Yujia , Li Yangling , Xian Miao , Zhou Qian , Yang Bo , Ying Meidan , He Qiaojun 
Published: April 2016

AbstractThe success of all-trans retinoic acid (ATRA) in differentiation therapy for patients with acute promyelocytic leukemia (APL) highly encourages researches to apply this therapy to other types of acute myeloid leukemia (AML). However, AML, with the exception of APL, fails to respond to differentiation therapy. Therefore, research strategies to further sensitize cells to retinoids and to extend the range of AMLs that respond to retinoids beyond APLs are urgently needed. In this study, we showed that TAK165, a HER2 inhibitor, exhibited a strong synergy with ATRA to promote AML cell differentiation. We observed that TAK165 sensitized the AML cells to ATRA-induced cell growth inhibition, G0/G1 phase arrest, CD11b expression, mature morphologic changes, NBT reduction and myeloid regulator expression. Unexpectedly, HER2 pathway might not be essential for TAK165-enhanced differentiation when combined with ATRA, while the enhanced differentiation was dependent on the activation of the RARα/STAT1 axis. Furthermore, the MEK/ERK cascade regulated the activation of STAT1. Taken together, our study is the first to evaluate the synergy of TAK165 and ATRA in AML cell differentiation and to assess new opportunities for the combination of TAK165 and ATRA as a promising approach for future differentiation therapy.
Idiopathic Spinal Cord Herniation—Case Report
Authors: Sacco Rogerio , Gepp Ricardo , Quiroga Marco , Souza Henrique , Aguiar Vitor , Santos Romel 
Published: April 2016

AbstractIdiopathic spinal cord herniation is a rare cause of progressive myelopathy, especially in the absence of a history of spinal or surgical trauma. The radiological diagnosis is made through a myelography or an MRI exam. The spinal cord is pushed anteriorly, buffering the dural defect and leading in most cases to Brown-Séquard syndrome. The present study describes the case of a male patient with a clinical picture of progressive thoracic myelopathy. In the clinical and radiological investigation, an idiopathic spinal cord herniation on the chest level was identified. During the surgery, the spinal cord was reduced to the natural site, taking its usual elliptical shape, and the dural defect was repaired with a dural substitute. The numbness of the patient improved, and the shocks in the lower limbs disappeared. A postoperative MRI confirmed the surgical reduction of the herniation and the restoration of the anterior cerebrospinal fluid (CSF) column to the spinal cord. The authors describe the clinical, radiological, intraoperative, and postoperative evolution.
Developing new pathways into the biomedical informatics field: the AMIA High School Scholars Program
Authors: Unertl Kim M , Finnell John T , Sarkar Indra Neil 
Published: April 2016

Abstract
Increasing access to biomedical informatics experiences is a significant need as the field continues to face workforce challenges. Looking beyond traditional medical school and graduate school pathways into the field is crucial for expanding the number of individuals and increasing diversity in the field. This case report provides an overview of the development and initial implementation of the American Medical Informatics Association (AMIA) High School Scholars Program. Initiated in 2014, the program’s primary goal was to provide dissemination opportunities for high school students engaged in biomedical informatics research. We discuss success factors including strong cross-institutional, cross-organizational collaboration and the high quality of high school student submissions to the program. The challenges encountered, especially around working with minors and communicating program expectations clearly, are also discussed. Finally, we present the path forward for the continued evolution of the AMIA High School Scholars Program.
First detection of 3He+ in the planetary nebula IC 418
Authors: Guzman-Ramirez L. , Rizzo J. R. , Zijlstra A. A. , García-Miró C. , Morisset C. , Gray M. D. 
Published: April 2016

Abstract
The 3He isotope is important to many fields of astrophysics, including stellar evolution, chemical evolution, and cosmology. The isotope is produced in low-mass stars which evolve through the planetary nebula (PN) phase. 3He abundances in PNe can help test models of the chemical evolution of the Galaxy. We present the detection of the 3He+ emission line using the single dish Deep Space Station 63, towards the PN IC 418. We derived a 3He/H abundance in the range 1.74 ± 0.8 × 10−3 to 5.8 ± 1.7 × 10−3, depending on whether part of the line arises in an outer ionized halo. The lower value for 3He/H ratio approaches values predicted by stellar models which include thermohaline mixing, but requires that large amounts of 3He are produced inside low-mass stars which enrich the interstellar medium (ISM). However, this overpredicts the 3He abundance in H ii regions, the ISM, and protosolar grains, which is known to be of the order of 10−5. This discrepancy questions our understanding of the evolution of the 3He, from circumstellar environments to the ISM.
Differential Effects of Azithromycin, Doxycycline, and Cotrimoxazole in Ingested Blood on the Vectorial Capacity of Malaria Mosquitoes
Authors: Gendrin Mathilde , Yerbanga Rakiswendé Serge , Ouedraogo Jean Bosco , Lefèvre Thierry , Cohuet Anna , Christophides George K. 
Published: April 2016

Abstract
Background.  The gut microbiota of malaria vector mosquitoes grows after a blood meal and limits Plasmodium infection. We previously showed that penicillin and streptomycin in the ingested blood affect bacterial growth and positively impact mosquito survival and permissiveness to Plasmodium. In this study, we examine the effects of doxycycline, azithromycin, and co-trimoxazole. All 3 antibiotics are used in mass drug administration programs and have antimicrobial activities against bacteria and various stages of malaria parasites.
Methods.  The effects of blood meal supplementation with antibiotics on the mosquito microbiota, lifespan, and permissiveness to Plasmodium falciparum were assessed.
Results.  Ingestion of any of the 3 antibiotics significantly affected the mosquito microbiota. Azithromycin decreased P falciparum infection load and mosquito lifespan, whereas at high concentrations, doxycycline increased P falciparum infection load. Co-trimoxazole negatively impacted infection intensity but had no reproducible effect on mosquito lifespan.
Conclusions.  Our data suggest that the overall effect of antibiotic treatment on parameters critical for mosquito vectorial capacity is drug specific. The negative effect of azithromycin on malaria transmission is consistent with current efforts for disease elimination, whereas additional, larger scale investigations are required before conclusions can be drawn about doxycycline.
A switching cost for motor planning
Authors: Orban de Xivry Jean-Jacques , Lefèvre Philippe 
Published: April 2016

AbstractMovement planning consists of choosing the endpoint of the movement and selecting the motor program that will bring the effector on the endpoint. It is widely accepted that movement endpoint is updated on a trial-by-trial basis with respect to the observed errors and that the motor program for a given movement follows the rules of optimal feedback control. Here, we show clear limitations of these predictions because of the existence of a switching cost for motor planning. First, this cost prevented participants from tuning their motor program appropriately for each individual trial. This was true even when the participants selected the width of the target that they reached toward or when they had learned the appropriate motor program previously. These data are compatible with the existence of a switching cost such as those found in cognitive studies. Interestingly, this cost of switching shares many features of costs reported in cognitive task switching experiments and, when tested in the same participants, was correlated with it. Second, we found that randomly changing the width of a target over the course of a reaching experiment prevents the motor system from updating the endpoint of movements on the basis of the performance on the previous trial if the width of the target has changed. These results provide new insights into the process of motor planning and how it relates to optimal control theory and to a selection by consequences process rather than to an error-based process for action selection.
Subtle stratification confounds estimates of heritability from rare variants
Authors: Bhatia Gaurav , Gusev Alexander , Loh Po-Ru , Finucane Hilary , Vilhjálmsson Bjarni J. , Ripke Stephan ,   Schizophrenia Working Group of the Psychiatric Genomics Consortium, Purcell Shaun , Stahl Eli , Daly Mark , de Candia Teresa R , Lee Sang Hong , Neale Benjamin M , Keller Matthew C. , Zaitlen Noah A. , Pasaniuc Bogdan , Patterson Nick , Yang Jian , Price Alkes L. 
Published: April 2016

AbstractGenome-wide significant associations generally explain only a small proportion of the narrow-sense heritability of complex disease (h2). While considerably more heritability is explained by all genotyped SNPs (hg2), for most traits, much heritability remains missing (hg2<h2). Rare variants, poorly tagged by genotyped SNPs, are a major potential source of the gap betweenhg2andh2. Recent efforts to assess the contribution of both sequenced and imputed rare variants to phenotypes suggest that substantial heritability may lie in these variants. Here we analyze sequenced SNPs, imputed SNPs and haploSNPs— haplotype variants constructed from within a sample, without using a reference panel— and show that studies of heritability from these variants may be strongly confounded by subtle population stratification. For example, when meta-analyzing heritability estimates from 22 randomly ascertained case-control traits from the GERA cohort, we observe a statistically significant increase in heritability explained by imputed SNPs even after correcting for principal components (PCs) from genotyped (or imputed) SNPs. However, this increase is eliminated when correcting for stratification using PCs from a larger number of haploSNPs. We note that subtle stratification may also impact estimates of heritability from array SNPs, although we find that this is generally a less severe problem. Overall, our results suggest that estimating the heritability explained by rare variants for case-control traits requires exquisite control for population stratification, but current methods may not provide this level of control.
Assembly of Long Error-Prone Reads Using de Bruijn Graphs
Authors: Lin Yu , Yuan Jeffrey , Kolmogorov Mikhail , Shen Max W. , Pevzner Pavel A. 
Published: April 2016

AbstractThe recent breakthroughs in assembling long error-prone reads (such as reads generated by Single Molecule Real Time technology) were based on the overlap-layout-consensus approach and did not utilize the strengths of the alternative de Bruijn graph approach to genome assembly. Moreover, these studies often assume that applications of the de Bruijn graph approach are limited to short and accurate reads and that the overlap-layout-consensus approach is the only practical paradigm for assembling long error-prone reads. Below we show how to generalize de Bruijn graphs to assemble long error-prone reads and describe the ABruijn assembler, which results in more accurate genome reconstructions than the existing state-of-the-art algorithms.
Effects of variable mutation rates and epistasis on the distribution of allele frequencies in humans
Authors: Harpak Arbel , Bhaskar Anand , Pritchard Jonathan K. 
Published: April 2016

AbstractThe site frequency spectrum (SFS) has long been used to study demographic history and natural selection. Here, we extend this summary by examining the SFS conditional on the alleles found at the same site in other species. We refer to this extension as the “phylogenetically-conditioned SFS” or cSFS. Using recent large-sample data from the Exome Aggregation Consortium (ExAC), combined with primate genome sequences, we find that human variants that occurred independently in closely related primate lineages are at higher frequencies in humans than variants with parallel substitutions in more distant primates. We show that this effect is largely due to sites with elevated mutation rates causing significant departures from the widely-used infinite sites mutation model. Our analysis also suggests substantial variation in mutation rates even among mutations involving the same nucleotide changes. We additionally find evidence for epistatic effects on the cSFS: namely, that parallel primate substitutions at nonsynonymous sites are more informative about constraint in humans when the parallel substitution occurs in a closely related species. In summary, we show that variable mutation rates and local sequence context are important determinants of the SFS in humans.
A Transferable Model For Chromosome Architecture
Authors: Pierro Michele Di , Zhang Bin , Aiden Erez Lieberman , Wolynes Peter G. , Onuchic José N. 
Published: April 2016

AbstractIn vivo, the human genome folds into a characteristic ensemble of three-dimensional structures. The mechanism driving the folding process remains unknown. We report a theoretical model for chromatin (MinimalChromatinModel) that explains the folding of interphase chromosomes and generates chromosome conformations consistent with experimental data. The energy landscape of the model was derived by using the maximum entropy principle and relies on two experimentally derived inputs: a classification of loci into chromatin types and a catalog of the positions of chromatin loops. First, we trained our energy function using the Hi-C contact map of chromosome 10 from human GM12878 lymphoblastoid cells. Then we used the model to perform molecular dynamics simulations producing an ensemble of 3D structures for all GM12878 autosomes. Finally, we used these 3D structures to generate contact maps. We found that simulated contact maps closely agree with experimental results for all GM12878 autosomes.The ensemble of structures resulting from these simulations exhibited unknotted chromosomes, phase separation of chromatin types, and a tendency for open chromatin to lie at the periphery of chromosome territories.One Sentence Summary:We report a model for chromatin that explains and accurately reproduces the three-dimensional structure of chromosomes in interphase.
Zika virus, a new threat for Europe?
Authors: Jupille Henri , Seixas Goncalo , Mousson Laurence , Sousa Carla A. , Failloux Anna-Bella 
Published: April 2016

AbstractBackground:Since its emergence in 2007 in Micronesia and Polynesia, the arthropod-borne flavivirus Zika virus (ZIKV) has spread in the Americas and the Caribbean, following first detection in Brazil in May 2015. The risk of ZIKV emergence in Europe increases as imported cases are repeatedly reported. Together with chikungunya virus (CHIKV) and dengue virus (DENV), ZIKV is transmitted byAedesmosquitoes. Any countries where these mosquitoes are present could be potential sites for future ZIKV outbreak.Methodology/Principal Findings:Mosquito females were challenged with an Asian genotype of ZIKV. Fully engorged mosquitoes were then maintained in insectary conditions (28°±1°C, 16h:8h light:dark cycle and 80% humidity). 16-24 mosquitoes from each population were examined at 3, 6, 9 and 14 days postinfection to estimate the infection, disseminated infection and transmission rates. Based on these experimental infections, we demonstrated thatAe. albopictusfrom France were not very susceptible to ZIKV.Conclusions/Significance:In combination with the restricted distribution and lower population densities of EuropeanAe. albopictus, our results corroborate the low risk for ZIKV to expand into most parts of Europe with the possible exception of the warmest regions bordering the Mediterranean coastline.Author summaryIn May 2015, local transmission of Zika virus (ZIKV) was reported in Brazil and since then, more than 1.5 million human cases have been reported in Latin America and the Caribbean. This arbovirus, primarily found in Africa and Asia, is mainly transmitted byAedesmosquitoes,Aedes aegyptiandAedes albopictus. Viremic travelers returning from America to European countries whereAe. albopictusis established can become the source for local transmission of ZIKV. In order to estimate the risk of seeding ZIKV into local mosquito populations, the ability of EuropeanAe. aegyptiandAe. albopictusto transmit ZIKV was measured using experimental infections. We demonstrated thatAe. albopictusandAe. aegyptifrom Europe were not very susceptible to ZIKV. The threat for a Zika outbreak in Europe should be limited.
Posterior inferotemporal cortex cells use multiple visual pathways to complement fine and coarse discriminations
Authors: Ponce C. R. , Lomber S. G. , Livingstone M. S. 
Published: April 2016

ABSTRACTIn the macaque monkey brain, posterior inferior temporal cortex (PIT) cells are responsible for visual object recognition. They receive concurrent inputs from visual areas V4, V3 and V2. We asked how these different anatomical pathways contribute to PIT response properties by deactivating them while monitoring PIT activity. Using cortical cooling of areas V2/V3 or V4 and a hierarchical model of visual recognition, we conclude that these distinct pathways do not transmit different classes of visual features, but serve instead to maintain a balance of local-and global-feature selectivity in IT.
Long Range Force Transmission in Fibrous Matrices Enabled by Tension-Driven Alignment of Fibers
Authors: Wang Hailong , Abhilash A.S. , Chen Christopher S. , Wells Rebecca G. , Shenoy Vivek B. 
Published: April 2016

AbstractCells can sense and respond to mechanical signals over relatively long distances across fibrous extracellular matrices. Recently proposed models suggest that long-range force transmission can be attributed to the nonlinear elasticity or fibrous nature of collagen matrices, yet the mechanism whereby fibers align remains unknown. Moreover, cell shape and anisotropy of cellular contraction are not considered in existing models, although recent experiments have shown that they play crucial roles. Here, we explore all of the key factors that influence long-range force transmission in cell-populated collagen matrices: alignment of collagen fibers, responses to applied force, strain stiffening properties of the aligned fibers, aspect ratios of the cells, and the polarization of cellular contraction. A constitutive law accounting for mechanically-driven collagen fiber reorientation is proposed. We systematically investigate the range of collagen fiber alignment using both finite element simulations and analytical calculations. Our results show that tension-driven collagen fiber alignment plays a crucial role in force transmission. Small critical stretch for fiber alignment, large fiber stiffness and fiber strain-hardening behavior enable long-range interaction. Furthermore, the range of collagen fiber alignment for elliptical cells with polarized contraction is much larger than that for spherical cells with diagonal contraction. A phase diagram showing the range of force transmission as a function of cell shape and polarization and matrix properties is presented. Our results are in good agreement with recent experiments, and highlight the factors that influence long-range force transmission, in particular tension-driven alignment of fibers. Our work has important relevance to biological processes including development, cancer metastasis and wound healing, suggesting conditions whereby cells communicate over long distances.
The gendered discourse of ‘equal opportunities for men and women’ in Iranian EFL textbooks
Authors: Salami Ali , Ghajarieh Amir 
Published: April 2016

Purpose
The purpose of this paper is to examine the representations of male and female social actors within the subversive gendered discourse of “equal opportunities for men and women” in Iranian English as a foreign language (EFL) textbooks.

Design/methodology/approach
From the methodological perspective, this study fused van Leeuwen’s (2003) “Social Actor Network Model” and Sunderland’s (2004) “Gendered Discourses Model”.

Findings
Data obtained from this study showed the subversive gendered discourse of “equal opportunities” was supported through such representations within a narrow perspective in line with dominant gender ideologies in Iran. The findings suggest the resistance against such subversive gendered discourse in Iranian EFL textbooks underpins gender norms and religious ideologies existing in Iran.

Originality/value
Such representations of male and female social actors in school textbooks show inclusive education and the discourse of “equal opportunities” have yet to be realised in education system of many countries, including Iran.
A social cognitive investigation of Australian independent school Boards as teams
Authors: Krishnan Aparna , Barnett Kerry , McCormick John , Newcombe Geoffrey 
Published: April 2016

Purpose
The purpose of this exploratory study was to investigate independent school Boards as teams using a social cognitive perspective. Specifically, the study investigated Board processes and the nature of relationships between Board member self-efficacy, Board collective efficacy and performance of independent school Boards in New South Wales, Australia.

Design/methodology/approach
A multiple case study design that used qualitative research methods was employed. An expert steering group provided advice on the categorization of governance structures. A stratified purposeful sample of eight independent school Boards within the Sydney metropolitan area, New South Wales Australia participated. Data were collected from individual, semi-structured, face-to-face interviews with the Head of school, Board Chair and two Board members from each school. The interviews were digitally recorded and transcribed verbatim. Data were analyzed using qualitative data analysis procedures suggested in the literature.

Findings
The findings provide evidence that for independent school Board members in this study, self-efficacy and collective efficacy beliefs were related to perceptions of Board performance. Board member self-efficacy and Board collective efficacy appeared to be linked. Self-efficacy beliefs were primarily based on mastery experiences. Collective efficacy (at the individual level) primarily was based on members’ perceptions of Board past performance.

Originality/value
This paper provides insight into individual Board member beliefs likely to shape processes associated with independent school Board performance in New South Wales, Australia. The study is one of only a few that have adopted an empirical and descriptive approach, rather than only providing normative direction and imperatives.