bluuebunny/crossref_metadata_2025_split huggingface dataset:
How secondary EU law is made
Authors: Arnull Anthony 
Published: May 2017

Abstract
The EU has a number of law-making procedures, which seek to reconcile swirling national, institutional, and political rivalries. Like all legislation, the measures they generate represent compromises, but they have on the whole been remarkably successful in achieving their objectives. ‘How secondary EU law is made’ outlines the ordinary legislative procedure, which applies in many important areas of EU competence, and the process of enhanced cooperation. It goes on to describe special legislative procedures and the range of legal acts that may be adopted. Finally, it considers whether the EU makes too much law and the democratic legitimacy of its law-making procedures.
Hierarchical probabilistic models for multiple gene/variant associations based on next-generation sequencing data
Authors: Vavoulis Dimitrios V , Taylor Jenny C , Schuh Anna 
Published: May 2017

AbstractMotivationThe identification of genetic variants influencing gene expression (known as expression quantitative trait loci or eQTLs) is important in unravelling the genetic basis of complex traits. Detecting multiple eQTLs simultaneously in a population based on paired DNA-seq and RNA-seq assays employs two competing types of models: models which rely on appropriate transformations of RNA-seq data (and are powered by a mature mathematical theory), or count-based models, which represent digital gene expression explicitly, thus rendering such transformations unnecessary. The latter constitutes an immensely popular methodology, which is however plagued by mathematical intractability.ResultsWe develop tractable count-based models, which are amenable to efficient estimation through the introduction of latent variables and the appropriate application of recent statistical theory in a sparse Bayesian modelling framework. Furthermore, we examine several transformation methods for RNA-seq read counts and we introduce arcsin, logit and Laplace smoothing as preprocessing steps for transformation-based models. Using natural and carefully simulated data from the 1000 Genomes and gEUVADIS projects, we benchmark both approaches under a variety of scenarios, including the presence of noise and violation of basic model assumptions. We demonstrate that an arcsin transformation of Laplace-smoothed data is at least as good as state-of-the-art models, particularly at small samples. Furthermore, we show that an over-dispersed Poisson model is comparable to the celebrated Negative Binomial, but much easier to estimate. These results provide strong support for transformation-based versus count-based (particularly Negative-Binomial-based) models for eQTL mapping.Availability and implementationAll methods are implemented in the free software eQTLseq: https://github.com/dvav/eQTLseqSupplementary informationSupplementary data are available at Bioinformatics online.
Finite-time distributed formation tracking control of multi-UAVs with a time-varying reference trajectory
Authors: Zhao Wei , Li Renfu , Zhang Huaipin 
Published: May 2017

Abstract
This article studies finite-time distributed formation tracking control of a second-order multi-unmanned aerial vehicle (UAV) system. To reduce the burden of the system’s computation and communication, a distributed framework is designed in the control of the formation configuration, in which a time-varying reference trajectory is known by the following UAVs as exogenous input that decides the UAVs moving target. Then, time-triggered and event-triggered consensus control protocols are proposed and theoretically proved to achieve the formation flight in finite time. Finally, a numerical simulation is conducted for the formation tracking control of a typical multi-UAV system to validate the effectiveness of the proposed control protocols.
Two-step interphase microtubule disassembly aids spindle morphogenesis
Authors: Mchedlishvili Nunu , Matthews Helen K. , Corrigan Adam , Baum Buzz 
Published: May 2017

AbstractEntry into mitosis triggers profound changes in cell shape and cytoskeletal organisation. Here, by studying microtubule remodelling in human flat mitotic cells, we identify a two-step process of interphase microtubule disassembly. First, a microtubule stabilizing protein, Ensconsin, is inactivated in prophase as a consequence of its phosphorylation downstream of Cdk1/CyclinB. This leads to a reduction in interphase microtubule stability that may help to fuel the growth of centrosomally-nucleated microtubules. The peripheral interphase microtubules that remain are then rapidly lost as the concentration of tubulin heterodimers falls following dissolution of the nuclear compartment boundary. Finally, we show that a failure to destabilize microtubules in prophase leads to the formation of microtubule clumps, which interfere with spindle assembly. Overall, this analysis highlights the importance of the stepwise remodelling of the microtubule cytoskeleton, and the significance of permeabilization of the nuclear envelope in coordinating the changes in cellular organisation and biochemistry that accompany mitotic entry.
Optimal number of spacers in CRISPR arrays
Authors: Martynov Alexander , Severinov Konstantin , Ispolatov Yaroslav 
Published: May 2017

AbstractWe estimate the number of spacers in a CRISPR array of a bacterium which maximizes its protection against a viral attack. The optimality follows from a competition between two trends: too few distinct spacers make the bacteria vulnerable to an attack by a virus with mutated corresponding protospacers, while an excessive variety of spacers dilutes the number of the CRISPR complexes armed with the most recent and thus most effective spacers. We first evaluate the optimal number of spacers in a simple scenario of an infection by a single viral species and later consider a more general case of multiple viral species. We find that depending on such parameters as the concentration of CRISPR-CAS interference complexes and its preference to arm with more recently acquired spacers, the rate of viral mutation, and the number of viral species, the predicted optimal array length lies within a range quite reasonable from the viewpoint of recent experiments.Author summaryCRISPR-Cas system is an adaptive immunity defense in bacteria and archaea against viruses. It works by accumulating in bacterial genome an array of spacers, or fragments of virus DNA from previous attacks. By matching spacers to corresponding parts of virus DNA called protospacers, CRISPR-Cas system identifies and destroys intruder DNA. Here we theoretically estimate the number of spacers that maximizes bacterial survival. This optimum emerges from a competition between two trends: More spacers allow a bacterium to hedge against mutations in viral protospacers. However, keeping too many spacers makes the older ones inefficient because of accumulation of mutations in corresponding protospacers in viruses. Thus, fewer CRISPR-Cas molecular machines are left armed with more efficient young spacers. We have shown that a higher efficiency of CRISPR-Cas system allows a bacterium to utilize more spacers, increasing the optimal array length. On contrary, a higher viral mutation rate makes older spacers useless and favors shorter arrays. A higher diversity in viral species reduces the efficiency of CRISPR-Cas but does not necessary lead to longer arrays. We think that our study provides a new viewpoint at a huge variety in the observed array lengths and adds relevance to evolutionary models of bacterial-phage coexistence.
The brain as an efficient and robust adaptive learner
Authors: Denève Sophie , Alemi Alireza , Bourdoukan Ralph 
Published: May 2017

AbstractUnderstanding how the brain learns to compute functions reliably, efficiently and robustly with noisy spiking activity is a fundamental challenge in neuroscience. Most sensory and motor tasks can be described as dynamical systems and could presumably be learned by adjusting connection weights in a recurrent biological neural network. However, this is greatly complicated by the credit assignment problem for learning in recurrent networks, e.g. the contribution of each connection to the global output error cannot be determined based only on locally accessible quantities to the synapse. Combining tools from adaptive control theory and efficient coding theories, we propose that neural circuits can indeed learn complex dynamic tasks with local synaptic plasticity rules as long as they associate two experimentally established neural mechanisms. First, they should receive top-down feedbacks driving both their activity and their synaptic plasticity. Second, inhibitory interneurons should maintain a tight balance between excitation and inhibition in the circuit. The resulting networks could learn arbitrary dynamical systems and produce irregular spike trains as variable as those observed experimentally. Yet, this variability in single neurons may hide an extremely efficient and robust computation at the population level.
Influence of non-metabolic microbial growth promotors (cAMP – activators) on the sensitivity to antimicrobials in the actually multiresistant microbial strains
Authors: Martynov Artur , Osolodchenko Tatyana , Farber Boris , Farber Sophya 
Published: May 2017

AbstractIntroductionThe control over multi-resistant nosocomial strains of microorganisms has been becoming increasingly urgent in recent years. We suggest a new paradigm that eliminates killing or inhibiting the growth of bacteria. Excluding bacteria death supresses the selection of resistant strains of microorganisms. We have developed such non-metabolite growth promoters, which in very low doses stimulate the rapid growth of many bacteria strains. The mechanism of action of the enhancers is caused by the activation of the cAMP high doses accumulation process in the microbial cells. cAMP itself is a substrate for phosphorylation including DNA polymerases.Materials and methodsThe susceptible culture collection resistance strainsPseudomonas aeruginosa MDR Kharkov IMI1, Acinetobacter baumanii MDR Kharkov-IMI1, andClebsiella pneumonia MDR Kharkov-IMI1were used. The following antimicrobial agents of known potency were evaluated: ciprofloxacin, polymyxin, amikacin. The same broth, but containing 0.001% enhancers (under patenting), has been used for further passaging for MDR strains. Characteristics of bacterial growth were determined in a medium compared at the control group – the broth without enhancers.Results and discussionEnhancers contribute to a significant increase in the antimicrobial sensitivity to polymyxin, ciprofloxacin and amikacin in multi-resistant strains of bacteria. Changes in the growth characteristics and antimicrobial sensitivity are observed only in the second passage that demonstrates the need for the further studies of the molecular mechanisms of the cAMP effect on the division and growth of microbial cells.
Parasite-driven replacement of a sexual by a closely related asexual taxon in nature
Authors: Lohr Jennifer N. , Haag Christoph R. 
Published: May 2017

AbstractAsexual species are thought to suffer more from coevolving parasites than related sexuals. Yet, this prediction may be modulated by the fact that closely related sexuals and asexuals often differ in respects other than reproductive mode. Here, we follow the frequency dynamics of sexual and asexualDaphnia pulexin a natural pond that was initially dominated by sexuals. However, coinciding with an epidemic of a microsporidian parasite infecting both sexuals and asexuals, the pond was rapidly taken over by the initially rare asexuals. We experimentally confirm that asexuals are less susceptible and also suffer less from the parasite once infected. These results show the ecological replacement of a sexual taxon by a closely related asexual taxon, as driven by parasites. We suggest that this replacement is, however, not directly connected with the reproductive mode, but rather due to the recent introduction and invasive nature of the asexuals studied.
Polycystic Ovary Syndrome as an Endogenous Alcoholic Polycystic Ovary Syndrome
Authors: Medeiros IC. , Lima JG. 
Published: May 2017

ABSTRACTPolycystic ovary syndrome (PCOS) is a growing worldwide public health problem that affects millions of women in their reproductive age. Despite being a very common disorder among women, there are still gaps regarding knowledge of disease mechanisms. In this respect, it was recently reported that acetaldehyde (ACD) is endogenously formed during normal ovarian steroidogenesis. The researchers demonstrated that in physiological concentrations ACD caused no detrimental effect on ovarian tissue. Contrariwise, in supraphysiological levels, ACD impairs granulosa cell differentiation, reduces ovulation, and decreases oocyte quality. Gut microbiota of patients with nonalcoholic fatty liver disease (NAFLD) produces significant quantities of endogenous ethanol (EE) and ACD. Because PCOS is closely linked to NAFLD, an ethanol-producing disorder, we hypothesize that it can be an endogenous alcoholic polycystic ovary syndrome (EAPCOS). The main findings of this study were that (i) the odds ratio of having polycystic ovaries is 30-fold greater in alcohol-exposed women than among unexposed controls; (ii) NAFLD/PCOS patients produce gonadotoxic quantities of EE; (iii) NAFLD/PCOS and alcoholic hepatitis individuals share similar liver expression levels of genes regulating high-km ethanol-metabolizing enzymes; (iv) NAFLD/PCOS and alcohol-tolerant drinkers share similar high-capacity to metabolize ethanol in the gut-liver axis; and (v) low blood alcohol concentration (BAC) in NAFLD/PCOS and alcohol-tolerant individuals stem from extensive alcohol degradation in gut-liver axis and significant fecal loss of ethanol. In summary, we provide mechanistic insights supporting the hypothesis that PCOS can be indeed an EAPCOS.
Bayesian Inference Of Phylogenetic Networks From Bi-allelic Genetic Markers
Authors: Zhu Jiafan , Wen Dingqiao , Yu Yun , Meudt Heidi M. , Nakhleh Luay 
Published: May 2017

AbstractPhylogenetic networks are rooted, directed, acyclic graphs that model reticulate evolutionary histories. Recently, statistical methods were devised for inferring such networks from either gene tree estimates or the sequence alignments of multiple unlinked loci. Bi-allelic markers, most notably single nucleotide polymorphisms (SNPs) and amplified fragment length polymorphisms (AFLPs), provide a powerful source of genome-wide data. In a recent paper, a method called SNAPP was introduced for statistical inference of species trees from unlinked bi-allelic markers. The generative process assumed by the method combined both a model of evolution for the bi-allelic markers, as well as the multispecies coalescent. A novel component of the method was a polynomial-time algorithm for exact computation of the likelihood of a fixed species tree via integration over all possible gene trees for a given marker. Here we report on a method for Bayesian inference of phylogenetic networks from bi-allelic markers. Our method significantly extends the algorithm for exact computation of phylogenetic network likelihood via integration over all possible gene trees. Unlike the case of species trees, the algorithm is no longer polynomial-time on all instances of phylogenetic networks. Furthermore, the method utilizes a reversible-jump MCMC technique to sample the posterior of phylogenetic networks given bi-allelic marker data. Our method has a very good performance in terms of accuracy and robustness as we demonstrate on simulated data, as well as a data set of multiple New Zealand species of the plant genusOurisia(Plantaginaceae). We implemented the method in the publicly available, open-source PhyloNet software package.Author summaryThe availability of genomic data has revolutionized the study of evolutionary histories and phylogeny inference. Inferring evolutionary histories from genomic data requires, in most cases, accounting for the fact that different genomic regions could have evolutionary histories that differ from each other as well as from that of the species from which the genomes were sampled. In this paper, we introduce a method for inferring evolutionary histories while accounting for two processes that could give rise to such differences across the genomes, namely incomplete lineage sorting and hybridization. We introduce a novel algorithm for computing the likelihood of phylogenetic networks from bi-allelic genetic markers and use it in a Bayesian inference method. Analyses of synthetic and empirical data sets show a very good performance of the method in terms of the estimates it obtains.
Altered neocortical gene expression, brain overgrowth and functional over-connectivity inChd8haploinsufficient mice
Authors: Suetterlin Philipp , Hurley Shaun , Mohan Conor , Riegman Kimberley L. H. , Pagani Marco , Caruso Angela , Ellegood Jacob , Galbusera Alberto , Crespo-Enriquez Ivan , Michetti Caterina , Yee Yohan , Ellingford Robert , Brock Olivier , Delogu Alessio , Francis-West Philippa , Lerch Jason P. , Scattoni Maria Luisa , Gozzi Alessandro , Fernandes Cathy , Basson M. Albert 
Published: May 2017

ABSTRACTTruncatingCHD8mutations are amongst the highest confidence risk factors for autism spectrum disorders (ASD) identified to date. Here, we report thatChd8heterozygous mice display increased brain size, motor delay, hypertelorism, pronounced hypoactivity and anomalous responses to social stimuli. Whereas gene expression in the neocortex is only mildly affected at mid-gestation, over 600 genes are differentially expressed in the early postnatal neocortex. Genes involved in cell adhesion and axon guidance are particularly prominent amongst the down-regulated transcripts. Resting-state functional MRI identified increased synchronised activity in cortico-hippocampal and auditory-parietal networks inChd8heterozygous mutant mice, implicating altered connectivity as a potential mechanism underlying the behavioural phenotypes. Together, these data suggest that altered brain growth and diminished expression of important neurodevelopmental genes that regulate long-range brain wiring are followed by distinctive anomalies in functional brain connectivity inChd8+/-mice. Human imaging studies have reported altered functional connectivity in ASD patients, with long-range under-connectivity seemingly more frequent. Our data suggest thatCHD8haploinsufficiency represents a specific subtype of ASD where neuropsychiatric symptoms are underpinned by long-range over-connectivity.
Evolutionary Isolation and Phylogenetic Diversity Loss Under Random Extinction Events
Authors: Steel Mike , Pourfaraj Vahab , Chaudhary Abhishek , Mooers Arne 
Published: May 2017

AbstractThe extinction of species at the present leads to the loss of ‘phylogenetic diversity’ (PD) from the evolutionary tree in which these species lie. Prior to extinction, the total PD present can be divided up among the species in various ways using measures of evolutionary isolation (such as ‘fair proportion’ and ‘equal splits’). However, the loss of PD when certain combinations of species become extinct can be either larger or smaller than the cumulative loss of the isolation values associated with the extinct species. In this paper, we show that for trees generated under neutral evolutionary models, the loss of PD under a null model of random extinction at the present can be predicted from the loss of the cumulative isolation values, by applying a non-linear transformation that is independent of the tree. Moreover, the error in the prediction provably converges to zero as the size of the tree grows, with simulations showing good agreement even for moderate sized trees (n= 64).
Transcription factors recognize DNA shape without nucleotide recognition
Authors: Samee Md. Abul Hassan , Bruneau Benoit G. , Pollard Katherine S. 
Published: May 2017

AbstractWe hypothesized that transcription factors (TFs) recognize DNA shape without nucleotide sequence recognition. Motivating an independent role for shape, many TF binding sites lack a sequence-motif, DNA shape adds specificity to sequence-motifs, and different sequences can encode similar shapes. We therefore asked if binding sites of a TF are enriched for specific patterns of DNA shape-features,e.g.,helical twist. We developed ShapeMF, which discovers these shape-motifsde novowithout taking sequence information into account. We find that most TFs assayed in ENCODE have shape-motifs and bind regulatory regions recognizing shape-motifs in the absence of sequence-motifs. When shape- and sequence-recognition co-occur, the two types of motifs can be overlapping, flanking, or separated by consistent spacing. Shape-motifs are prevalent in regions co-bound by multiple TFs. Finally, TFs with identical sequence motifs have different shape-motifs, explaining their binding at distinct locations. These results establish shape-motifs as drivers of TF-DNA recognition complementary to sequence-motifs.
Sizing implications of a regional aircraft for inner-city operations
Authors: Heinemann Philipp , Schmidt Michael , Will Felix , Kaiser Sascha , Jeßberger Christoph , Hornung Mirko 
Published: May 2017

Purpose
The paper aims to assess the potential of aircraft operation from city centres to achieve shortened travel times and the involved aircraft design process.

Design/methodology/approach
The paper describes the methodical approach and iterative procedure of the design process. An assessment of potential technologies is conducted to provide the required enhancements to fulfil the constraints following an inner-city operation. Operational procedures were analysed to reduce the noise propagation through flight path optimization. Furthermore, a ground-based assisted take-off system was conceived to lower required take-off field length and to prevent engine sizing just for the take-off case. Cabin design optimization for a fast turnaround has been conducted to ensure a wide utilization spectrum. The results prove the feasibility of an aircraft developed for inner city operation.

Findings
A detailed concept for a 60-passenger single aisle aircraft is proposed for an Entry-Into-Service year 2040 with a design range of 1,500 nautical miles for a load factor of 90 per cent. Although the design for Short Take-off and Landing and low noise operation had to be traded partly with cruise efficiency, a noteworthy reduction in fuel burn per passenger and nautical mile could be achieved against current aircraft.

Practical implications
The findings will contribute to the evaluation of the feasibility and impact of the Flightpath 2050 goal of a 4-h door-to-door by providing a feasible but ambitious example. Furthermore, it highlights possible bottlenecks and problems faced when realizing this goal.

Originality/value
The paper draws its value from the consideration of the overall sizing effects at aircraft level and from a holistic view on an inner-city airport/aircraft concept design for a 4-h door-to-door goal.