bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus
Authors: Corti Davide , Zhao Jincun , Pedotti Mattia , Simonelli Luca , Agnihothram Sudhakar , Fett Craig , Fernandez-Rodriguez Blanca , Foglierini Mathilde , Agatic Gloria , Vanzetta Fabrizia , Gopal Robin , Langrish Christopher J. , Barrett Nicholas A , Sallusto Federica , Baric Ralph S. , Varani Luca , Zambon Maria , Perlman Stanley , Lanzavecchia Antonio 
Published: July 2015

Significance
Middle East Respiratory Syndrome coronavirus (MERS-CoV) causes severe respiratory disease with a high mortality rate. There is no licensed vaccine or antiviral for MERS. Here we isolated for the first time, to our knowledge, a potent MERS-CoV–neutralizing antibody from memory B cells of an infected individual. This antibody binds to a novel site on the viral Spike protein, neutralizes by interfering with the binding to the cellular receptor CD26, and is highly effective both in prophylaxis and in therapy in a relevant mouse model. This antibody can be developed for prophylaxis, for postexposure prophylaxis, or for the treatment of severe MERS-CoV infections.
Activity-dependent BDNF release via endocytic pathways is regulated by synaptotagmin-6 and complexin
Authors: Wong Yu-Hui , Lee Chia-Ming , Xie Wenjun , Cui Bianxiao , Poo Mu-ming 
Published: July 2015

Significance
Brain-derived neurotrophic factor (BDNF) is a secreted neurotrophin known to mediate activity-dependent synaptic plasticity. Endogenously synthesized BDNF is normally stored and transported in dense core vesicles and secreted at synapses in response to activity. However, secreted BDNF may also be endocytosed by neurons and transported within neuronal cytoplasm in the form of endosomes. By monitoring the endocytosed BDNF bound to fluorescent quantum dots (BDNF-QDs), we found that endocytosed BDNF-QDs could be preferentially localized to postsynaptic sites in cultured hippocampal neurons and became exocytosed in response to synaptic activity. This synaptic release of endocytic BDNF requires a synaptotagmin isoform distinct from that regulates the secretion of dense core vesicles, and may serve as a source for activity-dependent secretion of synaptic BDNF.
Discrete approach to stochastic parametrization and dimension reduction in nonlinear dynamics
Authors: Chorin Alexandre J. , Lu Fei 
Published: July 2015

SignificanceMany problems in science are too large and/or too complex to be fully analyzed by standard methods of computation. We present an approach where such problems are treated statistically, and the statistical analysis and the equations actually solved are discrete rather than continuous. We connect our approach to well-known results in statistical physics, and demonstrate its effectiveness in a widely used test problem.
Gating of a mechanosensitive channel due to cellular flows
Authors: Pak On Shun , Young Y.-N. , Marple Gary R. , Veerapaneni Shravan , Stone Howard A. 
Published: July 2015

Significance
Mechanosensitive (MS) channels are membrane proteins that can be gated by membrane tension, and they play major roles in mechanosensation and mechanotransduction in cells. As a step in understanding the dynamics of a MS channel in membranes exposed to fluid flows, a multiscale continuum model is constructed to address how a MS channel in a vesicle membrane can be gated by flow-generated stresses in two physiological flows: planar shear flow and pressure-driven flow across a constriction channel. We demonstrate the opening/closing of a MS channel as a function of the flow strength and physical parameters. Our numerical results also suggest the possibility of utilizing fluid flows to deliver macromolecules (e.g., drugs) by gating MS channels reconstituted in liposomes in microfluidic platforms.
Generation of knock-in primary human T cells using Cas9 ribonucleoproteins
Authors: Schumann Kathrin , Lin Steven , Boyer Eric , Simeonov Dimitre R. , Subramaniam Meena , Gate Rachel E. , Haliburton Genevieve E. , Ye Chun J. , Bluestone Jeffrey A. , Doudna Jennifer A. , Marson Alexander 
Published: July 2015

Significance
T-cell genome engineering holds great promise for cancer immunotherapies and cell-based therapies for HIV, primary immune deficiencies, and autoimmune diseases, but genetic manipulation of human T cells has been inefficient. We achieved efficient genome editing by delivering Cas9 protein pre-assembled with guide RNAs. These active Cas9 ribonucleoproteins (RNPs) enabled successful Cas9-mediated homology-directed repair in primary human T cells. Cas9 RNPs provide a programmable tool to replace specific nucleotide sequences in the genome of mature immune cells—a longstanding goal in the field. These studies establish Cas9 RNP technology for diverse experimental and therapeutic genome engineering applications in primary human T cells.
Demographics of Shovelnose Sturgeon in the Lower Wabash River, Illinois
Authors: Nepal KC Vaskar , Colombo Robert E. , Frankland Leslie D. 
Published: July 2015

Abstract
With the closure of commercial fishing for Shovelnose Sturgeon Scaphirhynchus platorynchus in most reaches of the Mississippi and Missouri rivers, harvest may increase in other rivers. We studied the demographics of a commercially exploited Shovelnose Sturgeon population in the lower 322 km of the Wabash River, Illinois. During 2000–2013, 10,734 Shovelnose Sturgeon were captured by using DC and AC electrofishing, gill nets, hoop nets, trotlines, and benthic trawls. Of the captured individuals, 399 fish were recaptured. Electrofishing CPUE was the highest reported in any study on Shovelnose Sturgeon. Captured fish ranged between 61 and 909 mm FL (mean = 662 mm; median = 671 mm), but few fish were smaller than 500 mm. Although the fish were in good condition (mean relative weight = 89.9), there was a decreasing trend in mean condition over time. Shovelnose Sturgeon ranged in age from 0 to 25 years; 90% of the fish were between age 8 and age 19. Fish were fully recruited to the sampling gear at age 10; total annual mortality for fish older than 10 years was 20.6%. An empirical growth rate of 2.67 mm/year was observed for fish larger than 635 mm, with several individuals showing negative growth. The sex ratio was slightly skewed toward males (2.18 males : 1 female). The Shovelnose Sturgeon population in the lower Wabash River was generally healthy and stable and had characteristics comparable to those of the upper Wabash River population, with slow growth, large sizes, good condition, and low mortality.
Received December 19, 2014; acceptedMay 11, 2015
The era of stereotactic body radiotherapy for spinal metastases and the multidisciplinary management of complex cases
Authors: Kumar Rachit , Nater Anick , Hashmi Ahmed , Myrehaug Sten , Lee Young , Ma Lijun , Redmond Kristin , Lo Simon S. , Chang Eric L. , Yee Albert , Fisher Charles G. , Fehlings Michael G. , Sahgal Arjun 
Published: July 2015

AbstractSpinal metastases are increasingly becoming a focus of attention with respect to treating with locally “ablative” intent, as opposed to locally “palliative” intent. This is due to increasing survival rates among patients with metastatic disease, early detection as a result of increasing availability of spinal MRI, the recognition of the oligometastatic state as a distinct sub-group of favorable metastatic patients and the advent of stereotactic body radiotherapy (SBRT). Although conventionally fractionated radiation therapy has been utilized for decades, the rates of complete pain relief and local control for complex tumors are sub-optimal. SBRT has the advantage of delivering high total doses in few fractions (typically, 24 Gy in 1 or 2 fractions to 30–45 Gy in 5 fractions) that can be considered “ablative”. With mature clinical experience emerging among early adopters, we are realizing beyond efficacy the limitations of spine SBRT. In particular, toxicities such as vertebral compression fracture, and epidural disease progression as the most common pattern of local tumor progression. As a result, the multidisciplinary evaluation of cases prior to SBRT is emphasized with the intent to identify patients who could benefit from surgical stabilization or down-staging of epidural disease. The purpose of this review is to provide an overview of the current literature with respect to outcomes, technical details for safe delivery, patient selection criteria, common and uncommon side effects of therapy, and the increasing use of minimally invasive surgical techniques that can improve both safety and local control.
Self-organized patterning and morphogenesis in embryonic epithelia from antagonistic signals and fiber networks
Authors: Cummings F.W. , Lu Kai 
Published: July 2015

AbstractA number of universals can be observed in the developing embryos of all phyla. An attempt is made here to describe some of these with a simple model, one consisting of two mutually repelling regions of gene patterning produced by signaling pathways, two acting at each growth phase. The diffusion of ligands is short range, nearest or near neighbors, but the transcription patterns extend over many cellular diameters. The universals discussed are: gastrulation, formation of a blastopore, patterning of stem cells as surrounding compartments (propagating anew with each growth phase, to the adult), the origin of bilaterality, the prevalence of segmentation, and the general ability to regenerate and duplicate. The origin of organ sizes are determined by the parameters of the signaling pathways involved, independent of cell sizes or numbers. The important fiber mesh, or fiber network that can also extend over many cell diameters is also briefly discussed, and is seen as a partner with the signaling pathways in the overall patterning.
Long-term natural selection affects patterns of neutral divergence on the X chromosome more than the autosomes
Authors: Narang Pooja , Wilson Sayres Melissa A. 
Published: July 2015

AbstractNatural selection reduces neutral population genetic diversity near coding regions of the genome because recombination has not had time to unlink selected alleles from nearby neutral regions. For ten sub-species of great apes, including human, we show that long-term selection affects estimates of divergence on the X differently from the autosomes. Divergence increases with increasing distance from genes on both the X chromosome and autosomes, but increases faster on the X chromosome than autosomes, resulting in increasing ratios of X/A divergence in putatively neutral regions. Similarly, divergence is reduced more on the X chromosome in neutral regions near conserved regulatory elements than on the autosomes. Consequently estimates of male mutation bias, which rely on comparing neutral divergence between the X and autosomes, are twice as high in neutral regions near genes versus far from genes. Our results suggest filters for putatively neutral genomic regions differ between the X and autosomes.
GOTHiC, a simple probabilistic model to resolve complex biases and to identify real interactions in Hi-C data
Authors: Mifsud Borbala , Martincorena Inigo , Darbo Elodie , Sugar Robert , Schoenfelder Stefan , Fraser Peter , Luscombe Nicholas M. 
Published: July 2015

1.AbstractHi-C is one of the main methods for investigating spatial co-localisation of DNA in the nucleus. However, the raw sequencing data obtained from Hi-C experiments suffer from large biases and spurious contacts, making it difficult to identify true interactions. Existing methods use complex models to account for biases and do not provide a significance threshold for detecting interactions. Here we introduce a simple binomial probabilistic model that resolves complex biases and distinguishes between true and false interactions. The model corrects biases of known and unknown origin and yields a p-value for each interaction, providing a reliable threshold based on significance. We demonstrate this experimentally by testing the method against a random ligation dataset. Our method outperforms previous methods and provides a statistical framework for further data analysis, such as comparisons of Hi-C interactions between different conditions. GOTHiC is available as a BioConductor package (http://www.bioconductor.org/packages/release/bioc/html/GOTHiC.html).
Dis-integrating the fly: A mutational perspective on phenotypic integration and covariation
Authors: Haber Annat , Dworkin Ian 
Published: July 2015

AbstractThe structure of environmentally induced phenotypic covariation can influence the effective strength and magnitude of natural selection. Yet our understanding of the factors that contribute to and influence the evolutionary lability of such covariation is poor. Most studies have either examined environmental variation without accounting for covariation, or examined phenotypic and genetic covariation without distinguishing the environmental component. In this study we examined the effect of mutational perturbations on different properties of environmental covariation, as well as mean shape. We use strains ofDrosophila melanogasterbearing well-characterized mutations known to influence wing shape, as well as naturally-derived strains, all reared under carefully-controlled conditions and with the same genetic background. We find that mean shape changes more freely than the covariance structure, and that different properties of the covariance matrix change independently from each other. The perturbations affect matrix orientation more than they affect matrix eccentricity or total variance. Yet, mutational effects on matrix orientation do not cluster according to the developmental pathway that they target. These results suggest that it might be useful to consider a more general concept of ‘decanalization’, involving all aspects of variation and covariation.
Dating ancient human samples using the recombination clock
Authors: Moorjani Priya , Sankararaman Sriram , Fu Qiaomei , Przeworski Molly , Patterson Nick , Reich David 
Published: July 2015

AbstractThe study of human evolution has been revolutionized by inferences from ancient DNA analyses. Key to these is the reliable estimation of the age of ancient specimens. The current best practice is radiocarbon dating, which relies on characterizing the decay of radioactive carbon isotope (14C), and is applicable for dating up to 50,000-year-old samples. Here, we introduce a new genetic method that uses recombination clock for dating. The key idea is that an ancient genome has evolved less than the genomes of extant individuals. Thus, given a molecular clock provided by the steady accumulation of recombination events, one can infer the age of the ancient genome based on the number of missing years of evolution. To implement this idea, we take advantage of the shared history of Neanderthal gene flow into non-Africans that occurred around 50,000 years ago. Using the Neanderthal ancestry decay patterns, we estimate the Neanderthal admixture time for both ancient and extant samples. The difference in these admixture dates then provides an estimate of the age of the ancient genome. We show that our method provides reliable results in simulations. We apply our method to date five ancient Eurasian genomes with radiocarbon dates ranging between 12,000 to 45,000 years and recover consistent age estimates. Our method provides a complementary approach for dating ancient human samples and is applicable to ancient non-African genomes with Neanderthal ancestry. Extensions of this methodology that use older shared events may be able to date ancient genomes that fall beyond the radiocarbon frontier.SignificanceWe introduce a new genetic method for dating ancient human samples that uses the recombination clock. The main idea relies on the insight that an ancient genome lacks several thousand years of evolution compared to genomes of living individuals. To infer the age of ancient genomes, we take advantage of the shared history of Neanderthal gene flow into non-Africans that occurred around 50,000 years ago. By characterizing the dates of Neanderthal gene flow in ancient and extant genomes and quantifying the difference in these dates, we estimate the age of the ancient specimen. Our method is applicable for dating ancient samples more recent than the Neanderthal mixture event, so on par with radiocarbon dating, providing a complementary approach for dating.
SEX-DETector: a probabilistic approach to uncover sex chromosomes in non-model organisms
Authors: Muyle Aline , Käfer Jos , Zemp Niklaus , Mousset Sylvain , Picard Franck , Marais Gabriel AB 
Published: July 2015

AbstractData deposition:During the review process, the SEX-DETector galaxy workflow and associated test datasets are made available on the publicgalaxy.prabi.frserver. The data as well as the tool interface are visible to anonymous users, but to use them, you should register for an account (“user Register”), and import the data library “SEX-DETector” (“Shared Data Data Libraries”) into your history. More instructions can be found in the “readme” file in this library. The user manual for SEX-DETector is available here:https://lbbe.univ-lyon1.fr/Download-5251.html?lang=en.Paper submitted as a Genome Resource.We propose a probabilistic framework to infer autosomal and sex-linked genes from RNA-seq data of a cross for any sex chromosome type (XY, ZW, UV). Sex chromosomes (especially the nonrecombining and repeat-dense Y, W, U and V) are notoriously difficult to sequence. Strategies have been developed to obtain partially assembled sex chromosome sequences. However, most of them remain difficult to apply to numerous non-model organisms, either because they require a reference genome, or because they are designed for evolutionarily old systems. Sequencing a cross (parents and progeny) by RNA-seq to study the segregation of alleles and infer sex-linked genes is a cost-efficient strategy, which also provides expression level estimates. However, the lack of a proper statistical framework has limited a broader application of this approach. Tests on empirical data show that our method identifies many more sex-linked genes than existing pipelines, while making reliable inferences for downstream analyses. Simulations suggest few individuals are needed for optimal results. For species with unknown sex-determination system, the method can assess the presence and type (XY versus ZW) of sex chromosomes through a model comparison strategy. The method is particularly well optimised for sex chomosomes of young or intermediate age, which are expected in thousands of yet unstudied lineages. Any organism, including non-model ones for which nothing is known a priori, that can be bred in the lab, is suitable for our method. SEX-DETector is made freely available to the community through a Galaxy workflow.
Crystal structure of (E)-1-(1-hydroxynaphthalen-2-yl)-3-(2,3,4-trimethoxyphenyl)prop-2-en-1-one
Authors: Srividya J. , Reuben Jonathan D. , Revathi B. K. , Anbalagan G. 
Published: July 2015

The title compound, C22H20O5, is composed of a hydroxynaphthyl ring and a trimethoxyphenyl ring [the planes of which are inclined to one another by 21.61 (10)°] bridged by an unsaturated prop-2-en-1-one group. The mean plane of the prop-2-en-1-one group [–C(=O)—C=C–] is inclined to that of the naphthyl system and benzene rings by 3.77 (14) and 18.01 (16)°, respectively. There is an intramolecular O—H...O hydrogen bond present forming anS(6) ring motif. In the crystal, inversion-related molecules are linked by a slipped-parallel π–π interaction [intercentroid distance = 3.8942 (13) Å, interplanar distance = 3.478 (9) Å and slippage = 1.751 Å], and stack along the [101] direction. There are no other significant intermolecular interactions present.
Resources-for-infrastructure (R4I) swaps
Authors: Konijn Peter , van Tulder Rob 
Published: July 2015

Purpose
– This paper aims to understand the role resources-for-infrastructure (R4I) swaps play in internationalisation strategies, thereby contributing to a modern theory of the multinational enterprises (MNEs) based on experiences of rising power firms. Since 2004, the Chinese Government; state-owned policy banks; and oil, mining and construction corporations have used a relatively unique form of internationalisation through complex, large-scale R4I swaps in Africa.

Design/methodology/approach
– This paper uses a resource bundling perspective and political economy lens to analyse complex entry decisions and success, as well as the failure of R4I swaps. The paper is based on a comparative analysis of published case studies of R4I swaps in seven African countries complemented by field research by the first author.

Findings
– The findings show that, under very specific circumstances, R4I swaps can be considered as a successful internationalisation strategy. R4I swaps enable Chinese MNEs to build and maintain relationships with non-market elites that control access to natural resources and infrastructure contracts.

Research limitations/implications
– The sample of cases, although representing all relevant R4I-swaps, is too small to come for more quantitative conclusions on success/failure factors.

Practical implications
– R4I swaps are a very unlikely model for Western MNEs, as they lack the necessary country-specific competitive advantages and institutional mechanisms.

Originality/value
– To the authors’ knowledge, this is the first comprehensive study of all relevant Chinese R4I swaps in Africa and contains original data from fieldwork in Ghana and D.R. Congo.
Responding to the rising power “threat”
Authors: Horner Rory 
Published: July 2015

Purpose
– This paper aims to explore how established multinational enterprises (MNEs) have responded to the perceived threat from rising power firms by seeking to alter the intellectual property institutional environment in key emerging economies.

Design/methodology/approach
– The key place of emerging economies in the efforts of established MNEs to seek patent law change is discussed. Two case studies review developments related to pharmaceutical patents in India and South Africa, highlighting the influence of MNEs in driving policy change and the contested nature of their actions.

Findings
– While India and South Africa both present evidence of MNEs seeking to influence pharmaceutical patent laws, distinct differences emerge. In India, most MNE pressure has been in response to the emergence of an active domestic industry and a patent law oriented towards generic entry, while the MNE priority in South African has been geared towards maintaining MNE dominance and a system which leads to generous granting of patents.

Practical implications
– Managers and decision-makers seeking to invest in emerging economies must take account of a plethora of institutions present, which may be better suited towards local industrial and consumer interests and may prompt resistance to any established MNE-led attempt at institutional change.

Originality/value
– The article offers a comparative perspective on pharmaceutical patent laws in India and South Africa, which have been subject to significant contestation by policymakers, civil society organisations and both rising power and established MNEs. The comparison explores and questions the increasingly widespread “institutional void” thesis in international business.