bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal features of word-initial /s/+stop clusters in bilingual Mandarin–English children and monolingual English children and adults
Authors: YANG JING 
Published: May 2017

AbstractThis study investigated the durational features of English word-initial /s/+stop clusters produced by bilingual Mandarin (L1)–English (L2) children and monolingual English children and adults. The participants included two groups of five- to six-year-old bilingual children: low proficiency in the L2 (Bi-low) and high proficiency in the L2 (Bi-high), one group of age-matched English children, and one group of English adults. Each participant produced a list of English words containing /sp, st, sk/ at the word-initial position followed by /a, i, u/, respectively. The absolute durations of the clusters and cluster elements and the durational proportions of elements to the overall cluster were measured. The results revealed that Bi-high children behaved similarly to the English monolinguals whereas Bi-low children used a different strategy of temporal organization to coordinate the cluster components in comparison to the English monolinguals and Bi-high children. The influence of language experience and continuing development of temporal features in children were discussed.
DELAYED STATE FEEDBACK CONTROL FOR PERIODIC-REVIEW INVENTORY SYSTEMS
Authors: ZHANG B.-L. , YANG C. 
Published: May 2017

We investigate delayed state feedback control of a periodic-review inventory management system with perishable goods. The stock under consideration is replenished from multiple supply sources. By using delayed states as well as current states of the inventory system, a delayed feedback $H_{\infty }$ control strategy is developed to mitigate bullwhip effects of the system. Some conditions on the existence of the delayed feedback $H_{\infty }$ controller are derived. It is found through simulation results that the proposed delayed $H_{\infty }$ control scheme is capable of improving the performance of the inventory management significantly. In addition, the delayed controller is better than the traditional delay-free $H_{\infty }$ controller.
HTSvis: a web app for exploratory data analysis and visualization of arrayed high-throughput screens
Authors: Scheeder Christian , Heigwer Florian , Boutros Michael 
Published: May 2017

Abstract

Summary
Arrayed high-throughput screens (HTS) cover a broad range of applications using RNAi or small molecules as perturbations and specialized software packages for statistical analysis have become available. However, exploratory data analysis and integration of screening results has remained challenging due to the size of the data sets and the lack of user-friendly tools for interpretation and visualization of screening results. Here we present HTSvis, a web application to interactively visualize raw data, perform quality control and assess screening results from single to multi-channel measurements such as image-based screens. Per well aggregated raw and analyzed data of various assay types and scales can be loaded in a generic tabular format.

Availability and implementation
HTSvis is distributed as an open-source R package, downloadable from https://github.com/boutroslab/HTSvis and can also be accessed at http://htsvis.dkfz.de.

Supplementary information
Supplementary data are available at Bioinformatics online.
Treatment Outcomes of Third-line Antiretroviral Regimens in HIV-infected Thai Adolescents
Authors: Prasitsuebsai Wasana , Sophonphan Jiratchaya , Chokephaibulkit Kulkanya , Wongsawat Jurai , Kanjanavanit Suparat , Kosalaraksa Pope , Ngampiyakul Chaiwat , Sangkla Pakarat , Hansudewechakul Rawiwan , Kerr Stephen J. , Puthanakit Thanyawee , Ananworanich Jintanat 
Published: May 2017

Background:
Efficacy and safety data of third-line antiretroviral (ARV) regimens in adolescents are limited.

Methodology:
This study enrolled HIV-infected Thais who were treated with third-line regimens consisting of darunavir/ritonavir (DRV/r), etravirine (ETR), tipranavir/ritonavir or raltegravir.

Results:
Fifty-four adolescents 2–17 years of age were enrolled from 8 sites and followed for 48 weeks. Reasons for switch were second-line failure (n = 44) and toxicity to second-line regimens (n = 10). At switching to third-line ARV, the median age (interquartile range) was 14.3 (12.4–15.4) years. Genotypes at time of second-line failure (n = 44) were M184V (77%), ≥4 thymidine analogue mutations (25%), non-nucleoside reverse transcriptase inhibitor–resistant associated mutation (RAM) (80%), ETR-RAM score ≥4 (14%), any lopinavir-RAM (59%) and ≥1 major DRV-RAM (41%). The third-line regimens had a median of 4 (min–max, 4–6) drugs and included ETR/DRV/r (43%), DRV/r (33%), ETR (17%), tipranavir/ritonavir (2%) or raltegravir/DRV/r/ (4%). The median CD4 (interquartile range) increased from 16% (12–21) at third-line switch to 21% (18–25) and 410 (172–682) to 607 (428–742) cells/mm3 at 48 weeks (P < 0.001). HIV RNA declined from 3.9 (2.9–4.9) to 1.6 (1.6–3.0) log10 copies/mL (P < 0.001) and 33/50 (66%) had levels <50 copies/mL at 48 weeks. Seventeen (31%) had HIV-RNA ≥1000 copies/mL; about half due to poor adherence; genotyping in 13 of these adolescents revealed ETR-RAM score ≥4 in 2 (15%) and ≥1 major DRV-RAM in 7 (54%).

Conclusions:
Third-line ARV therapy was well tolerated and resulted in virologic suppression in 70% of adolescents at 1 year. Poor adherence and limited ARV options are major problems in the long-term management of adolescents with HIV.
Coalescent Processes with Skewed Offspring Distributions and non-Equilibrium Demography
Authors: Matuszewski Sebastian , Hildebrandt Marcel E. , Achaz Guillaume , Jensen Jeffrey D. 
Published: May 2017

AbstractNon-equilibrium demography impacts coalescent genealogies leaving detectable, well-studied signatures of variation. However, similar genomic footprints are also expected under models of large reproductive skew, posing a serious problem when trying to make inference. Furthermore, current approaches consider only one of the two processes at a time, neglecting any genomic signal that could arise from their simultaneous effects, pre-venting the possibility of jointly inferring parameters relating to both offspring distribution and population history. Here, we develop an extended Moran model with exponential population growth, and demonstrate that the underlying ancestral process converges to a time-inhomogeneous psi-coalescent. However, by applying a non-linear change of time scale – analogous to the Kingman coalescent – we find that the ancestral process can be rescaled to its time-homogeneous analogue, allowing the process to be simulated quickly and efficiently. Furthermore, we derive analytical expressions for the expected site-frequency spectrum under the time-inhomogeneous psi-coalescent and develop an approximate-likelihood framework for the joint estimation of the coalescent and growth parameters. By means of extensive simulation, we demonstrate that both can be estimated accurately from whole-genome data. In addition, not accounting for demography can lead to serious biases in the inferred coalescent model, with broad implications for genomic studies ranging from ecology to conservation biology. Finally, we use our method to analyze sequence data from Japanese sardine populations and find evidence of high variation in individual reproductive success, but few signs of a recent demographic expansion.
Responses to mechanically and visually cued water waves in the nervous system of the medicinal leech
Authors: Lehmkuhl Andrew M. , Muthusamy Arunkumar , Wagenaar Daniel A. 
Published: May 2017

Summary statementCues from water movement help aquatic predators find their prey. We study how the nervous system of the medicinal leech processes visual and mechanical information derived from surface waves.AbstractSensitivity to water waves is a key modality by which aquatic predators can detect and localize their prey. For one such predator, the medicinal leech,Hirudo verbana, behavioral responses to visual and mechanical cues from water waves are well documented. Here, we quantitatively characterized the response patterns of a multisensory interneuron, the S cell, to mechanically and visually cued water waves. The frequency dependence of the S-cell response matched the behavioral response well, in that sensitivity was higher for low frequencies in the visual modality and for high frequencies in the mechanical modality. We demonstrated that neither the cephalic ganglia nor the tail brain is required for the S cell to respond to visually cued water waves. The direction of spike propagation within the S- cell system did follow the direction of wave propagation under certain circumstances, but it is unlikely that downstream neuronal targets can use this information. In terms of overall firing rate, the S cell response was not direction selective. Accordingly we propose a role for the S cell in the detection of waves but not in the localization of their source.
Integrated Computing and Tracking System for Centralized High-Throughput Genetic Analysis: a Case Study
Authors: Stilp Adrienne M. , Gogarten Stephanie M. , Laurie Cathy C. , Sofer Tamar 
Published: May 2017

AbstractThe Genetic Analysis Center (GAC) of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) developed an Integrated Computing and Tracking system (ICT) in order to perform genome-wide and other genetic association studies automatically and efficiently, while documenting all analysis specifications. This system provides easy-to-use analysis set-up and computing procedures, automatic reports, and analysis search functionality due to integration with an on-site database. In this paper we describe the ICT and demonstrate how it satisfies key principles of reproducible research, while respecting constraints and challenges arising from using very large, restricted access, human-subjects data. This case study may benefit other groups that have similar requirements for high-throughput analysis execution and management.
Role of the membrane cholesterol-glycosphingolipid complex as a ‘transistor’ to regulate GSL receptor function and signaling of both lipids
Authors: Novak Anton , Lingwood Clifford 
Published: May 2017

AbstractCholesterol and glycosphingolipids (GSL) are the major species that accumulate in plasma membrane lipid rafts. These complexes imbue the membrane with increased order, which in turn, plays a central role in the transmembrane signaling foci lipid rafts provide. In addition, both GSL and cholesterol binding can mediate (separate) signal pathways. We have shown that cholesterol and GSLs however, form a complex in which the GSL sugar is reoriented from a membrane perpendicular to parallel format, becoming largely unavailable for exogenous ligand binding. Similarly, the steroid hydroxyl is masked, restricting access of cholesterol ligands. This was observed in model and cell membranes and in human tumour frozen tissue sections. We now show the order of exogenous ligand binding plays a significant role to determine the extent of GSL or cholesterol receptor activity. Ligand binding to cholesterol enhances subsequent GSL recognition and vice versa, suggesting that ligand binding to “free” receptor (membrane perpendicular GSL carbohydrate, nonmasked cholesterol) can result in partial dissociation of the GSL/cholesterol complex to allow additional GSL ligand and cholesterol ligand binding. Since many GSLs can complex with membrane cholesterol, the binding of a single cholesterol ligand may unmask cholesterol-complexed GSL for increased binding of both a single or multiple GSL-specific ligands. We show that multiple cholesterol-masked GSLs can be coincident in tissues. This provides a mechanism for GSL-dependent signal amplification and diversification, representing a biological ‘transistor’, regulating amplitude and potentially, diversity of GSL signaling. The process represents a new mechanism of ‘cross-talk’ between GSL and cholesterol signaling. This is of clinical importance since we have found cholesterol/GSL masking applies to monoclonal anti GSL antibodies in development and in current use as antineoplastic therapeutics.
A model for adult organ resizing demonstrates stem cell scaling through a tunable commitment rate
Authors: Du XinXin , O’Brien Lucy Erin , Riedel-Kruse Ingmar 
Published: May 2017

AbstractMany adult organs grow or shrink to accommodate different physiological demands. Often, as total cell number changes, stem cell number changes proportionally in a phenomenon called ‘stem cell scaling’. The cellular behaviors that give rise to scaling are unknown. Here we study two complementary theoretical models of the adult Drosophila midgut, a stem cell-based organ with known resizing dynamics. First, we derive a differential equations model of midgut resizing and show that the in vivo kinetics of growth can be recapitulated if the rate of fate commitment depends on the tissue’s stem cell proportion. Second, we develop a twodimensional simulation of the midgut and find that proportion-dependent commitment rate and stem cell scaling can arise phenomenologically from the stem cells’ exploration of physical tissue space during its lifetime. Together, these models provide a biophysical understanding of how stem cell scaling is maintained during organ growth and shrinkage.
Quantitative Models Identify Histone Signatures of Poised Genes Prior to Cellular Differentiation
Authors: Tian Rui 
Published: May 2017

AbstractBackgroundRecent studies have shown that histone marks are involved in pre-programming gene fates during cellular differentiation. Bivalent domains (marked by both H3K4me3 and H3K27me3) have been proposed to act in the histone pre-patterning of poised genes; however, bivalent genes could also resolve into monovalent silenced states during differentiation. Thus, the histone signatures of poised genes need to be more precisely characterized.ResultsUsing a support vector machine (SVM), we show that the collective histone modification data from human blood hematopoietic cells (HSCs) could predict poised genes with fairly high predictive accuracy within the model of directed erythrocyte differentiation from HSCs. Surprisingly, models with single histone marks (e.g., H3K4me3 or H2A.Z) could reach comparable predictive powers to the full model built with all of the nine histone marks. We also derived an H2A.Z and H3K9me3-based Naive Bayesian model for inferring poised genes, and the validity of this model was supported by data from several other pluripotent/multipotent cells (including mouse ES cells).ConclusionOur work represents a systematic quantitative study that verified that histone marks play a role in pre-programming the activation or repression of specific genes during cellular differentiation. Our results suggest that the relative quantities of H2A.Z modification and H3K9me3 modification are important in determining a corresponding gene’s fate during cellular differentiation.
Role of competition in the strain structure of rotavirus under invasion and reassortment
Authors: Zinder Daniel , Riolo Maria A , Woods Robert J. , Pascual Mercedes 
Published: May 2017

ABSTRACTThe role of competitive interactions in the formation and coexistence of viral strains remains unresolved. Neglected aspects of existing strain theory are that viral pathogens are repeatedly introduced from animal sources and readily exchange their genes. The combined effect of introduction and reassortment opposes strain structure, in particular the predicted stable coexistence of antigenically differentiated strains under strong frequency-dependent selection mediated by cross-immunity. Here we use a stochastic model motivated by rotavirus, the most common cause of childhood diarrheal mortality, to investigate serotype structure under these conditions. We describe a regime in which the transient coexistence of distinct strains emerges despite only weak cross-immunity, but is disturbed by invasions of new antigenic segments that reassort into existing backgrounds. We find support for this behavior in global rotavirus sequence data and present evidence for the displacement of new strains towards open antigenic niches. Our work extends previous work to bacterial and viral pathogens that share these rotavirus-like characteristics, with important implications for the effects of interventions such as vaccination on strain composition, and for the understanding of the factors promoting emergence of new subtypes.
A gated relaxation oscillator controls morphogenetic movements in bacteria
Authors: Guzzo Mathilde , Murray Seán M. , Martineau Eugénie , Lhospice Sébastien , Baronian Grégory , My Laetitia , Zhang Yong , Espinosa Leon , Vincentelli Renaud , Bratton Benjamin P. , Shaevitz Joshua W. , Molle Virginie , Howard Martin , Mignot Tâm 
Published: May 2017

SummaryDynamic control of cell polarity is of critical importance for many aspects of cellular development and motility. InMyxococcus xanthus, a G-protein and its cognate GTPase-activating protein establish a polarity axis that defines the direction of movement of the cell and which can be rapidly inverted by the Frz chemosensory system. Although vital for collective cell behaviours, how Frz triggers this switch has remained unknown. Here, we use genetics, imaging and mathematical modelling to show that Frz controls polarity reversals via a gated relaxation oscillator. FrzX, which we newly identify as the primary Frz output, provides the gating and thus acts as the trigger for reversals. Slow relocalisation of the polarity protein RomR then creates a refractory period during which another switch cannot be triggered. A secondary Frz output, FrzZ, decreases this delay allowing rapid reversals when required. This architecture thus results in a highly tunable switch that allows a wide range of motility responses.
Experimental Evolution of Insect Immune Memory VS. Pathogen Resistance
Authors: Khan Imroze , Prakash Arun , Agashe Deepa 
Published: May 2017

ABSTRACTUnder strong pathogen pressure, insects often evolve resistance to infection. Many insects are also protected via immune memory (‘immune priming’), whereby sub-lethal exposure to a pathogen enhances survival after secondary infection. To understand the evolution and consequences of these immune responses, we imposed strong pathogen selection on flour beetles (Tribolium castaneum), infecting them withBacillus thuringiensis(Bt) for 11 generations. Populations injected first with heat-killed and then live Bt each generation evolved high basal resistance against multiple Bt strains. In contrast, all populations injected only with a high dose of live Bt evolved less effective but strain-specific priming response. Control populations injected with heat-killed Bt did not evolve priming; and in the ancestor, priming was effective only against a low Bt dose. Thus, pathogens can select for rapid modulation of insect priming ability, leading to divergent immune strategies (generalized resistance vs. specific immune priming) with distinct mechanisms and adaptive benefits.
The condensin complex is a mechanochemical motor that translocates along DNA
Authors: Terekawa Tsuyoshi , Bisht Shveta , Eeftens Jorine M. , Dekker Cees , Haering Christian H. , Greene Eric C. 
Published: May 2017

One Sentence SummarySingle-molecule imaging reveals that eukaryotic condensin is a highly processive DNA-translocating motor complex.AbstractCondensin plays crucial roles in chromosome organization and compaction, but the mechanistic basis for its functions remains obscure. Here, we use single-molecule imaging to demonstrate that Saccharomyces cerevisiae condensin is a molecular motor capable of ATP hydrolysis-dependent translocation along double-stranded DNA. Condensin’s translocation activity is rapid and highly processive, with individual complexes traveling an average distance of ≥10 kilobases at a velocity of ∼60 base pairs per second. Our results suggest that condensin may take steps comparable in length to its ∼50-nanometer coiled-coil subunits, suggestive of a translocation mechanism that is distinct from any reported DNA motor protein. The finding that condensin is a mechanochemical motor has important implications for understanding the mechanisms of chromosome organization and condensation.
Tacrolimus rescues endothelial ALK1 loss-of-function signaling and improves HHT vascular pathology
Authors: Ruiz Santiago , Chandakkar Pallavi , Zhao Haitian , Papoin Julien , Chatterjee Prodyot K. , Christen Erica , Metz Christine N. , Blanc Lionel , Campagne Fabien , Marambaud Philippe 
Published: May 2017

AbstractHereditary hemorrhagic telangiectasia (HHT) is a genetic vascular disorder arising from endothelial cell (EC) proliferation and hypervascularization, for which no cure exists. Because HHT is caused by loss-of-function mutations in BMP9-ALK1-Smad1/5/8 signaling, interventions aimed at activating this pathway are of therapeutic value. By screening FDA-approved drug libraries, we identified tacrolimus (FK-506) as a potent activator of Smad1/5/8 in BMP9-challenged reporter cells. In primary ECs, tacrolimus activated Smad1/5/8 to oppose the pro-angiogenic gene expression signature associated with ALK1 loss-of-function, by notably reducing Dll4 expression. In these cells, tacrolimus also inhibited Akt and p38 stimulation by VEGF. In the BMP9/10-immunodepleted postnatal retina—a mouse model of HHT vascular pathology—tacrolimus activated endothelial Smad1/5/8 and prevented the Dll4 overexpression and hypervascularization associated with this model. Finally, tacrolimus stimulated Smad1/5/8 in cells transfected with BMP9-unresponsive ALK1 HHT mutants and in HHT patient blood outgrowth ECs. We propose that tacrolimus repurposing has therapeutic potential in HHT.
Physiological assembly of functionally active 30S ribosomal subunits fromin vitrosynthesized parts
Authors: Li Jun , Wassie Brook , Church George M. 
Published: May 2017

ABSTRACTSynthetic ribosomesin vitrocan facilitate engineering translation of novel polymers, identifying ribosome biogenesis central components, and paving the road to constructing replicating systems from defined biochemical components. Here, we report functional syntheticEscherichia coli30S ribosomal subunits constructed using a defined, purified cell free system under physiological conditions. We test hypotheses about key components of natural ribosome biogenesis pathway as required for efficient function – including integration of 16S rRNA modification, cofactors facilitated ribosome assembly and protein synthesis in the same compartmentin vitro. We observe ~17% efficiency for fully synthetic 30S and ~70% efficiency fromin vitrotranscribed 16S rRNA assembled with natural proteins. We observe up to 5 fold improvement over previous crude extracts. We suggest extending the minimal list of components required for central-dogma replication from the 151 gene products previously reported to at least 180 to allow the speed and accuracy of macromolecular synthesis to approach nativeE. colivalues.