bluuebunny/crossref_metadata_2025_split huggingface dataset:
hotspot: software to support sperm-typing for investigating recombination hotspots
Authors: Odenthal-Hesse Linda , Dutheil Julien Y. , Klötzl Fabian , Haubold Bernhard 
Published: April 2016

Abstract
Motivation: In many organisms, including humans, recombination clusters within recombination hotspots. The standard method for de novo detection of recombinants at hotspots is sperm typing. This relies on allele-specific PCR at single nucleotide polymorphisms. Designing allele-specific primers by hand is time-consuming. We have therefore written a package to support hotspot detection and analysis.
Results: hotspot consists of four programs: asp looks up SNPs and designs allele-specific primers; aso constructs allele-specific oligos for mapping recombinants; xov implements a maximum-likelihood method for estimating the crossover rate; six, finally, simulates typing data.
Availability and Implementation: hotspot is written in C. Sources are freely available under the GNU General Public License from http://github.com/evolbioinf/hotspot/
Contact: haubold@evolbio.mpg.de
Supplementary information: Supplementary data are available at Bioinformatics online.
Na + , HCO 3
− -cotransporter NBCn1 increases pH i gradients, filopodia, and migration of smooth muscle cells and promotes arterial remodelling
Authors: Boedtkjer Ebbe , Bentzon Jacob F. , Dam Vibeke S. , Aalkjaer Christian 
Published: April 2016

Abstract

Aims
Arterial remodelling can cause luminal narrowing and obstruct blood flow. We tested the hypothesis that cellular acid–base transport facilitates proliferation and migration of vascular smooth muscle cells (VSMCs) and enhances remodelling of conduit arteries.

Methods and results
N a + , HC O 3 − -cotransport via NBCn1 (Slc4a7) mediates net acid extrusion and controls steady-state intracellular pH (pH i ) in VSMCs of mouse carotid arteries and primary aortic explants. Carotid arteries undergo hypertrophic inward remodelling in response to partial or complete ligation in vivo , but the increase in media area and thickness and reduction in lumen diameter are attenuated in arteries from NBCn1 knock-out compared with wild-type mice. With CO2/HCO3− present, gradients for pH i (∼0.2 units magnitude) exist along the axis of VSMC migration in primary explants from wild-type but not NBCn1 knock-out mice. Knock-out or pharmacological inhibition of NBCn1 also reduces filopodia and lowers initial rates of VSMC migration after scratch-wound infliction. Interventions to reduce H + -buffer mobility (omission of CO2/HCO3− or inhibition of carbonic anhydrases) re-establish axial pH i gradients, filopodia, and migration rates in explants from NBCn1 knock-out mice. The omission of CO2/HCO3− also lowers global pH i and inhibits proliferation in primary explants.

Conclusion
Under physiological conditions (i.e. with CO2/HCO3− present), NBCn1-mediated HCO3− uptake raises VSMC pH i and promotes filopodia, VSMC migration, and hypertrophic inward remodelling. We propose that axial pH i gradients enhance VSMC migration whereas global acidification inhibits VSMC proliferation and media hypertrophy after carotid artery ligation. These findings support a key role of acid–base transport, particularly via NBCn1, for development of occlusive artery disease.
Systemically Significant Prices
Authors: Hockett Robert C. , Omarova Saule T. 
Published: April 2016

Abstract
Some prices and indices in domestic or global markets take on particular market-wide importance. This can occur either because (i) they are associated with ubiquitous inputs to production, (ii) they are associated with highly popular asset classes, (iii) by convention they tend to be used as benchmarks in determining other prices, or (iv) some combination of the above. Examples include prevailing wage and salary rates, certain energy and commodity prices, and such indices and borrowing rates as the Standard & Poor’s 500, the Federal Funds Rate, and the Libor and Euribor interbank lending rate benchmarks.
We call such prices and indices ‘systemically important’ prices and indices, or ‘SIPIs’. Over the long term, these prices and indices tend towards certain statistical mean values that reflect determinants that can plausibly be treated as ‘fundamentals’, be these demographic, technological, or global-quantity-rooted in character. At times, however, SIPIs can move out of alignment with mean values and associated fundamentals owing to distortions stemming from missing information, recursive collective action problems (including ‘noise’ trading and ‘herd’ behaviour), or even deliberately manipulative behaviour on the part of influential or colluding market actors.
We develop a general account of systemically important prices and indices as well as of the market vulnerabilities to which they can give rise. We then develop a menu of regulatory strategies for addressing these vulnerabilities in manners that protect markets’ capacities to translate fundamental values into (more) accurate prices or indices when such prices or indices are systemically important. Key to the effort is recognizing that what we propose is in some cases what regulators are committed to doing already in maintaining market integrity, and in other cases is what central banks do already in determining appropriate money rental (‘interest‘) rates and securing them through open market operations.
Transcriptome data analysis reveals correlation between developmentally altered gene expression and offspring phenotype in epigenetic inheritance
Authors: Sharma Abhay 
Published: April 2016

AbstractA recent study investigated sperm mediated inheritance of diet induced metabolic phenotype, reported underlying regulation of MERVL targets and ribosomal protein genes in embryos, and suggested that the altered regulation observed may cause placentation defects which can secondarily result in abnormal metabolism. An analysis of available transcriptomic data however reveals a direct link between the developmentally altered genes and the offspring phenotype.
GenRank: an R/Bioconductor package for prioritization of candidate genes
Authors: Kanduri Chakravarthi , Järvelä Irma 
Published: April 2016

AbstractSummary:Modern high-throughput studies often yield long lists of genes, of which a fraction are of high relevance to the phenotype of interest. To prioritize the candidate genes of complex genetic traits, our R/Bioconductor package GenRank provides methods that are based on convergent evidence obtained from multiple independent evidence layers. The package facilitates an extensible framework that allows a further addition of novel methods for candidate gene prioritization.Availability and Implementation:The methods are implemented in R and available as a package in Bioconductor repository (http://bioconductor.org/packages/GenRank/).Contact:chakra.kanduri@gmail.com
The effects of population size histories on estimates of selection coefficients from time-series genetic data
Authors: Jewett Ethan M. , Steinrücken Matthias , Song Yun S. 
Published: April 2016

ABSTRACTMany approaches have been developed for inferring selection coefficients from time series data while accounting for genetic drift. However, the improvement in inference accuracy that can be attained by modeling drift is unknown. Here, by comparing maximum likelihood estimates of selection coefficients that account for the true population size history with estimates that ignore drift, we address the following questions: how much can modeling the population size history improve estimates of selection coefficients? How much can mis-inferred population sizes hurt inferences of selection coefficients? We conduct our analysis under the discrete Wright-Fisher model by deriving the exact probability of an allele frequency trajectory in a population of time-varying size and we replicate our results under the diffusion model by extending the exact probability of a frequency trajectory derived by Steinrückenet al. (2014) to the case of a piecewise constant population. For both the discrete Wright-Fisher and diffusion models, we find that ignoring drift leads to estimates of selection coefficients that are nearly as accurate as estimates that account for the true population history, even when population sizes are small and drift is high. In populations of time-varying size, estimates of selection coefficients that ignore drift are similar in accuracy to estimates that rely on crude, yet reasonable, estimates of the population history. These results are of interest because inference methods that ignore drift are widely used in evolutionary studies and can be many orders of magnitude faster than methods that account for population sizes.
Using Google Earth to improve management of threatened limestone karst ecosystems in Peninsular Malaysia
Authors: Liew Thor-Seng , Price Liz , Clements Gopalasamy Reuben 
Published: April 2016

AbstractBiodiversity conservation is now about prioritisation, especially in a world with limited resources and so many habitats and species in need of protection. However, we cannot prioritise effectively if historical and current information on a particular habitat or species remains scattered. Several good platforms have been created to help users to find, use and create biodiversity information. However, good platforms for sharing habitat information for threatened ecosystems are still lacking. Limestone hills are an example of threatened ecosystems that harbour unique biodiversity, but are facing intensifying anthropogenic disturbances. As limestone is a vital resource for the construction industry, it is not possible to completely halt forest degradation and quarrying in developing countries such as Malaysia, where 445 limestone hills have been recorded in the peninsula to date. As such, there is an urgent need to identify which hills must be prioritised for conservation. To make decisions based on sound science, collating spatial and biological information on limestone hills into a publicly accessible database is critical. Here, we compile Malaysia’s first limestone hill GIS map for 445 limestone hills in the peninsula based on information from geological reports and scientific literature. To assist in conservation prioritisation efforts, we quantify characteristics of limestone hills in terms of size, degree of isolation, and spatial distribution patterns and also assessed the degree of habitat disturbance of each limestone hill in terms of buffer area forest degradation and quarrying activity. All this information is stored in a KMZ file and can be accessed through the Google Earth interface. This product should not be viewed as a final output containing basic limestone hill information. Rather, this database is a foundational platform for users to collect, store, update and manipulate spatial and biological data from limestone hills to better inform decisions regarding their management.
Retrotransposon proliferation coincident with the evolution of dioecy inAsparagus
Authors: Harkess Alex , Mercati Francesco , Abbate Loredana , McKain Michael , Pires J. Chris , Sala Tea , Sunseri Francesco , Falavigna Agostino , Leebens-Mack Jim 
Published: April 2016

AbstractCurrent phylogenetic sampling reveals that dioecy and an XY sex chromosome pair evolved once or possibly twice in the genusAsparagus. Although there appear to be some lineage-specific polyploidization events, the base chromosome number of 2n=2x=20 is relatively conserved across theAsparagusgenus. Regardless, dioecious species tend to have larger genomes than hermaphroditic species. Here we test whether this genome size expansion in dioecious species is related to a polyploidization and subsequent chromosome fusion or retrotransposon proliferation in dioecious species. We first estimate genome sizes or use published values for four hermaphrodites and four dioecious species distributed across the phylogeny and show that dioecious species typically have larger genomes than hermaphroditic species. Utilizing a phylogenomic approach we find no evidence for ancient polyploidization contributing to increased genome sizes of sampled dioecious species. We do find support for an ancient whole genome duplication event predating the diversification of theAsparagusgenus. Repetitive DNA content of the four hermaphroditic and four dioecious species was characterized based on randomly sampled whole genome shotgun sequencing and common elements were annotated. Across our broad phylogenetic sampling,Ty-1 Copiaretroelements in particular have undergone a marked proliferation in dioecious species. In the absence of a detectable whole genome duplication event, retrotransposon proliferation is the most likely explanation for the precipitous increase in genome size in dioeciousAsparagusspecies.
Assessment of pharmacogenomic agreement
Authors: Safikhani Zhaleh , El-Hachem Nehme , Quevedo Rene , Smirnov Petr , Goldenberg Anna , Juul Birkbak Nicolai , Mason Christopher E. , Hatzis Christos , Shi Leming , Aerts Hugo JWL , Quackenbush John , Haibe-Kains Benjamin 
Published: April 2016

AbstractIn 2013 we published an analysis demonstrating that drug response data and gene-drug associations reported in two independent large-scale pharmacogenomic screens, Genomics of Drug Sensitivity in Cancer1(GDSC) and Cancer Cell Line Encyclopedia2(CCLE), were inconsistent3. The GDSC and CCLE investigators recently reported that their respective studies exhibit reasonable agreement and yield similar molecular predictors of drug response4, seemingly contradicting our previous findings3. Reanalyzing the authors’ published methods and results, we found that their analysis failed to account for variability in the genomic data and more importantly compared different drug sensitivity measures from each study, which substantially deviate from our more stringent consistency assessment. Our comparison of the most updated genomic and pharmacological data from the GDSC and CCLE confirms our published findings that the measures of drug response reported by these two groups are not consistent5. We believe that a principled approach to assess the reproducibility of drug sensitivity predictors is necessary before envisioning their translation into clinical settings.
Wild-type U2AF1 antagonizes the splicing program characteristic of U2AF1-mutant tumors and is required for cell survival
Authors: Fei Dennis Liang , Motowski Hayley , Chatrikhi Rakesh , Prasad Sameer , Yu Jovian , Gao Shaojian , Kielkopf Clara , Bradley Robert K. , Varmus Harold 
Published: April 2016

AbstractWe have asked how the common S34F mutation in the splicing factor U2AF1 regulates alternative splicing in lung cancer, and why wild-type U2AF1 is retained in cancers with this mutation. A human lung epithelial cell line was genetically modified so thatU2AF1S34F is expressed from one of the two endogenous U2AF1 loci. By altering levels of mutant or wild-type U2AF1 in this cell line and by analyzing published data on human lung adenocarcinomas, we show that S34F-associated changes in alternative splicing are proportional to the ratio of S34F:wild-type gene products and not to absolute levels of either the mutant or wild-type factor. Preferential recognition of specific 3′ splice sites in S34F-expressing cells is largely explained by differential in vitro RNA-binding affinities of mutant versus wild-type U2AF1 for those same 3′ splice sites. Finally, we show that lung adenocarcinoma cell lines bearingU2AF1mutations do not require the mutant protein for growthin vitroorin vivo. In contrast, wild-type U2AF1 is required for survival, regardless of whether cells carry theU2AF1S34F allele. Our results provide mechanistic explanations of the magnitude of splicing changes observed inU2AF1-mutant cells and why tumors harboringU2AF1mutations always retain an expressed copy of the wild-type allele.Author SummaryLarge-scale genomics studies have identified recurrent mutations in many genes that fall outside the conventional domain of proto-oncogenes. They include genes encoding factors that mediate RNA splicing; mutations affecting four of these genes are present in up to half of proliferative myeloid disorders and in a significant number of solid tumors, including lung adenocarcinoma. Here we have characterized several properties of a common mutant version of the U2AF1 splicing factor, a component of the U2 auxiliary factor complex, in lung cells. We have found that mutant-associated changes in splice site selection are primarily influenced by the ratio of mutant and wild-type U2AF1 gene products; thus increasing wild-type U2AF1 levels represses the mutant-induced splicing program. We show that the altered splice site preferences of mutant U2AF1 can be attributed to changes in its binding to relevant 3′ splice sites. We also show that mutant U2AF1 is different from some oncogenes: the growth properties of lung cancer cell lines carrying the mutant allele are unaffected by loss of the mutant gene, while the wild-type allele is absolutely required for survival. These results advance our understanding of the molecular determinants of the mutant-associated splicing program, and they highlight previously unappreciated roles of wild-type U2AF1 in the presence of the recurrentU2AF1S34F mutation.
Inventory of cultivatable populations of S-cycling, fermentative, Fe-reducing, and aerobic heterotrophic bacteria from salt marsh sediments
Authors: Emerson David , Lydell Cynthia M. 
Published: April 2016

ABSTRACTA survey was carried out of the dominant chemotrophic groups of bacteria inhabiting surface salt marsh sediments in the Virginia Coastal Reserve (VCR) on the Atlantic coast of Virginia. Total direct cell counts were carried out on all samples. Aerobic heterotrophs, sulfur oxidizers, sulfate reducing bacteria (SRB), sulfur disproportionaters, Fe-reducing (FeRB) and fermentative bacteria were all quantified by most probable number (MPN) at four different sites that ranged in spatial scale from a few meters to 15 km apart. The sites were sampled every 3 – 4 months over a two year period. Total cell counts were quite consistent temporally at each of the sites, and ranged from a high of 1.4 × 1010cells. gdw-1to a low of 8 × 108cells. gdw-1. Recoveries of all culturable bacteria were also site dependent and ranged from a minimum of 0.4% to a maximum of 40% of the total cell count. Aerobic bacteria were the dominant recovered population at all of the sites, followed by sulfur-oxidizing bacteria. Together these two groups accounted for >75% of the total recovered bacteria at each of the sites. The populations of anaerobic groups fluctuated significantly; S-disproportionating and SRB were most abundant followed by FeRB and fermenters. On average, all the anaerobes were in the same order of magnitude of abundance (107cells. gdw-1). Overall, these results suggest that aerobic bacteria consistently predominated in the top 10 cm of the marsh sediments, and that autotrophy related to sulfur oxidation and disproportionation may be important, but under studied processes in salt marsh ecosystems.
Unsupervised spike sorting for large scale, high density multielectrode arrays
Authors: Hilgen Gerrit , Sorbaro Martino , Pirmoradian Sahar , Muthmann Jens-Oliver , Kepiro Ibolya E. , Ullo Simona , Juarez Ramirez Cesar , Puente Encinas Albert , Maccione Alessandro , Berdondini Luca , Murino Vittorio , Sona Diego , Cella Zanacchi Francesca , Sernagor Evelyne , Hennig Matthias H. 
Published: April 2016

AbstractA new method for automated spike sorting for recordings with high density, large scale multielectrode arrays is presented. Exploiting the dense sampling of single neurons by multiple electrodes, we obtain an efficient, low-dimensional representation of detected spikes consisting of estimated spatial spike locations and dominant spike shape features, which enables fast and reliable clustering into single units. Millions of events can be sorted in minutes, and the method is parallelized and scales better than quadratically with the number of detected spikes. We demonstrate this method using recordings with a 4,096 channel array, and present validation based on anatomical imaging, optogenetic stimulation and model-based quality control. A comparison with semi-automated, shape-based spike sorting exposes significant limitations of conventional methods. Our analysis shows that it is feasible to reliably isolate the activity of hundreds to thousands of neurons in a single recording, and that dense, multi-channel probes substantially aid reliable spike sorting.
Thermo-mechanical challenges of reflowed lead-free solder joints in surface mount components: a review
Authors: Lau Chun Sean , Khor C.Y. , Soares D. , Teixeira J.C. , Abdullah M.Z. 
Published: April 2016

PurposeThe purpose of the present study was to review the thermo-mechanical challenges of reflowed lead-free solder joints in surface mount components (SMCs). The topics of the review include challenges in modelling of the reflow soldering process, optimization and the future challenges in the reflow soldering process. Besides, the numerical approach of lead-free solder reliability is also discussed.Design/methodology/approachLead-free reflow soldering is one of the most significant processes in the development of surface mount technology, especially toward the miniaturization of the advanced SMCs package. The challenges lead to more complex thermal responses when the PCB assembly passes through the reflow oven. The virtual modelling tools facilitate the modelling and simulation of the lead-free reflow process, which provide more data and clear visualization on the particular process.FindingsWith the growing trend of computer power and software capability, the multidisciplinary simulation, such as the temperature and thermal stress of lead-free SMCs, under the influenced of a specific process atmosphere can be provided. A simulation modelling technique for the thermal response and flow field prediction of a reflow process is cost-effective and has greatly helped the engineer to eliminate guesswork. Besides, simulated-based optimization methods of the reflow process have gained popularity because of them being economical and have reduced time-consumption, and these provide more information compared to the experimental hardware. The advantages and disadvantages of the simulation modelling in the reflow soldering process are also briefly discussed.Practical implicationsThis literature review provides the engineers and researchers with a profound understanding of the thermo-mechanical challenges of reflowed lead-free solder joints in SMCs and the challenges of simulation modelling in the reflow process.Originality/valueThe unique challenges in solder joint reliability, and direction of future research in reflow process were identified to clarify the solutions to solve lead-free reliability issues in the electronics manufacturing industry.