bluuebunny/crossref_metadata_2025 huggingface dataset:
PEPSI-Dock: a detailed data-driven protein–protein interaction potential accelerated by polar Fourier correlation
Authors: Neveu Emilie , Ritchie David W , Popov Petr , Grudinin Sergei
Published: September 2016

Motivation

Docking prediction algorithms aim to find the native conformation of a complex of proteins from knowledge of their unbound structures. They rely on a combination of sampling and scoring methods, adapted to different scales. Polynomial Expansion of Protein Structures and Interactions for Docking (PEPSI-Dock) improves the accuracy of the first stage of the docking pipeline, which will sharpen up the final predictions. Indeed, PEPSI-Dock benefits from the precision of a very detailed data-driven model of the binding free energy used with a global and exhaustive rigid-body search space. As well as being accurate, our computations are among the fastest by virtue of the sparse representation of the pre-computed potentials and FFT-accelerated sampling techniques. Overall, this is the first demonstration of a FFT-accelerated docking method coupled with an arbitrary-shaped distance-dependent interaction potential.

Results

First, we present a novel learning process to compute data-driven distant-dependent pairwise potentials, adapted from our previous method used for rescoring of putative protein–protein binding poses. The potential coefficients are learned by combining machine-learning techniques with physically interpretable descriptors. Then, we describe the integration of the deduced potentials into a FFT-accelerated spherical sampling provided by the Hex library. Overall, on a training set of 163 heterodimers, PEPSI-Dock achieves a success rate of 91% mid-quality predictions in the top-10 solutions. On a subset of the protein docking benchmark v5, it achieves 44.4% mid-quality predictions in the top-10 solutions when starting from bound structures and 20.5% when starting from unbound structures. The method runs in 5–15 min on a modern laptop and can easily be extended to other types of interactions.

Availability and Implementation

https://team.inria.fr/nano-d/software/PEPSI-Dock.

Contact

sergei.grudinin@inria.fr
SWORD—a highly efficient protein database search
Authors: Vaser Robert , Pavlović Dario , Šikić Mile
Published: September 2016

Motivation

Protein database search is one of the fundamental problems in bioinformatics. For decades, it has been explored and solved using different exact and heuristic approaches. However, exponential growth of data in recent years has brought significant challenges in improving already existing algorithms. BLAST has been the most successful tool for protein database search, but is also becoming a bottleneck in many applications. Due to that, many different approaches have been developed to complement or replace it. In this article, we present SWORD, an efficient protein database search implementation that runs 8–16 times faster than BLAST in the sensitive mode and up to 68 times faster in the fast and less accurate mode. It is designed to be used in nearly all database search environments, but is especially suitable for large databases. Its sensitivity exceeds that of BLAST for majority of input datasets and provides guaranteed optimal alignments.

Availability and Implementation

Sword is freely available for download from https://github.com/rvaser/sword

Contact

robert.vaser@fer.hr and mile.sikic@fer.hr

Supplementary information

Supplementary data are available at Bioinformatics online.
ModuleAlign: module-based global alignment of protein–protein interaction networks
Authors: Hashemifar Somaye , Ma Jianzhu , Naveed Hammad , Canzar Stefan , Xu Jinbo
Published: September 2016

Motivation

As an increasing amount of protein–protein interaction (PPI) data becomes available, their computational interpretation has become an important problem in bioinformatics. The alignment of PPI networks from different species provides valuable information about conserved subnetworks, evolutionary pathways and functional orthologs. Although several methods have been proposed for global network alignment, there is a pressing need for methods that produce more accurate alignments in terms of both topological and functional consistency.

Results

In this work, we present a novel global network alignment algorithm, named ModuleAlign, which makes use of local topology information to define a module-based homology score. Based on a hierarchical clustering of functionally coherent proteins involved in the same module, ModuleAlign employs a novel iterative scheme to find the alignment between two networks. Evaluated on a diverse set of benchmarks, ModuleAlign outperforms state-of-the-art methods in producing functionally consistent alignments. By aligning Pathogen–Human PPI networks, ModuleAlign also detects a novel set of conserved human genes that pathogens preferentially target to cause pathogenesis.

Availability

http://ttic.uchicago.edu/∼hashemifar/ModuleAlign.html

Contact

canzar@ttic.edu or j3xu.ttic.edu

Supplementary information

Supplementary data are available at Bioinformatics online.
Genome wide predictions of miRNA regulation by transcription factors
Authors: Ruffalo Matthew , Bar-Joseph Ziv
Published: September 2016

Motivation

Reconstructing regulatory networks from expression and interaction data is a major goal of systems biology. While much work has focused on trying to experimentally and computationally determine the set of transcription-factors (TFs) and microRNAs (miRNAs) that regulate genes in these networks, relatively little work has focused on inferring the regulation of miRNAs by TFs. Such regulation can play an important role in several biological processes including development and disease. The main challenge for predicting such interactions is the very small positive training set currently available. Another challenge is the fact that a large fraction of miRNAs are encoded within genes making it hard to determine the specific way in which they are regulated.

Results

To enable genome wide predictions of TF–miRNA interactions, we extended semi-supervised machine-learning approaches to integrate a large set of different types of data including sequence, expression, ChIP-seq and epigenetic data. As we show, the methods we develop achieve good performance on both a labeled test set, and when analyzing general co-expression networks. We next analyze mRNA and miRNA cancer expression data, demonstrating the advantage of using the predicted set of interactions for identifying more coherent and relevant modules, genes, and miRNAs. The complete set of predictions is available on the supporting website and can be used by any method that combines miRNAs, genes, and TFs.

Availability and Implementation

Code and full set of predictions are available from the supporting website: http://cs.cmu.edu/~mruffalo/tf-mirna/.

Contact

zivbj@cs.cmu.edu

Supplementary information

Supplementary data are available at Bioinformatics online.
Extending partial haplotypes to full genome haplotypes using chromosome conformation capture data
Authors: Ben-Elazar Shay , Chor Benny , Yakhini Zohar
Published: September 2016

Motivation

Complex interactions among alleles often drive differences in inherited properties including disease predisposition. Isolating the effects of these interactions requires phasing information that is difficult to measure or infer. Furthermore, prevalent sequencing technologies used in the essential first step of determining a haplotype limit the range of that step to the span of reads, namely hundreds of bases. With the advent of pseudo-long read technologies, observable partial haplotypes can span several orders of magnitude more. Yet, measuring whole-genome-single-individual haplotypes remains a challenge. A different view of whole genome measurement addresses the 3D structure of the genome—with great development of Hi-C techniques in recent years. A shortcoming of current Hi-C, however, is the difficulty in inferring information that is specific to each of a pair of homologous chromosomes.

Results

In this work, we develop a robust algorithmic framework that takes two measurement derived datasets: raw Hi-C and partial short-range haplotypes, and constructs the full-genome haplotype as well as phased diploid Hi-C maps. By analyzing both data sets together we thus bridge important gaps in both technologies—from short to long haplotypes and from un-phased to phased Hi-C. We demonstrate that our method can recover ground truth haplotypes with high accuracy, using measured biological data as well as simulated data. We analyze the impact of noise, Hi-C sequencing depth and measured haplotype lengths on performance. Finally, we use the inferred 3D structure of a human genome to point at transcription factor targets nuclear co-localization.

Availability and Implementation

The implementation available at https://github.com/YakhiniGroup/SpectraPh.

Contact

zohar.yakhini@gmail.com

Supplementary information

Supplementary data are available at Bioinformatics online.
Edge-based sensitivity analysis of signaling networks by using Boolean dynamics
Authors: Trinh Hung-Cuong , Kwon Yung-Keun
Published: September 2016

Motivation

Biological networks are composed of molecular components and their interactions represented by nodes and edges, respectively, in a graph model. Based on this model, there were many studies with respect to effects of node-based mutations on the network dynamics, whereas little attention was paid to edgetic mutations so far.

Results

In this paper, we defined an edgetic sensitivity measure that quantifies how likely a converging attractor is changed by edge-removal mutations in a Boolean network model. Through extensive simulations based on that measure, we found interesting properties of highly sensitive edges in both random and real signaling networks. First, the sensitive edges in random networks tend to link two end nodes both of which are susceptible to node-knockout mutations. Interestingly, it was analogous to an observation that the sensitive edges in human signaling networks are likely to connect drug-target genes. We further observed that the edgetic sensitivity predicted drug-targets better than the node-based sensitivity. In addition, the sensitive edges showed distinguished structural characteristics such as a lower connectivity, more involving feedback loops and a higher betweenness. Moreover, their gene-ontology enrichments were clearly different from the other edges. We also observed that genes incident to the highly sensitive interactions are more central by forming a considerably large connected component in human signaling networks. Finally, we validated our approach by showing that most sensitive interactions are promising edgetic drug-targets in p53 cancer and T-cell apoptosis networks. Taken together, the edgetic sensitivity is valuable to understand the complex dynamics of signaling networks.

Contact

kwonyk@ulsan.ac.kr

Supplementary information

Supplementary data are available at Bioinformatics online.
On cross-conditional and fluctuation correlations in competitive RNA networks
Authors: Sánchez-Taltavull Daniel , MacLeod Matthew , Perkins Theodore J
Published: September 2016

Motivation

In competitive endogenous RNA (ceRNA) networks, different mRNAs targeted by the same miRNA can ‘cross-talk’ by absorbing miRNAs and relieving repression on the other mRNAs. This creates correlations in mRNA expression even without direct interaction. Most previous theoretical study of cross-talk has focused on correlations in stochastic fluctuations of mRNAs around their steady state values. However, the experimentally known examples of cross-talk do not involve single-cell fluctuations, but rather bulk tissue-level changes between conditions, such as due to differentiation or disease. In our study, we quantify for the first time both fluctuational and cross-conditional cross-talk in chemical kinetic models of miRNA–mRNA interaction networks. We study the parameter regions under which these different types of cross-talk arise, and how they are affected by network structure.

Results

We find that while a network may support both fluctuational and cross-conditional cross-talk, the parameter regimes under which each type of cross-talk tends to emerge are rather different. Consistent with previous studies, fluctuational cross-talk occurs when miRNA and mRNA expression levels are ‘balanced’, whereas cross-conditional cross-talk tends to emerge when average miRNA levels are high and average mRNA levels are low. Conversely, cross-conditional miRNA cross-talk—a little-discussed phenomenon—is greatest when miRNA levels are low and mRNA levels are high. We show that the parameter ranges where cross-talk is maximized can, to some degree, be predicted based on network structure. Indeed, we find that the dominant effect of network structure on correlations happens through the effect of network structure on the overall balance between miRNA and mRNA expression. However, it is not the only effect, as we find that the density of connections between miRNAs and mRNAs in larger networks increases cross-talk without altering the expression balance.

Conclusion

Our results deepen the theoretical understanding of cross-talk in ceRNA networks, and have implications for the experimental identification of ceRNA cross-talk phenomena.

Availability and Implementation

Simulation software available upon request.

Contact

tperkins@ohri.ca
Stronger sink demand for metabolites supports dominance of the apical bud in etiolated growth
Authors: Buskila Yossi , Sela Noa , Teper-Bamnolker Paula , Tal Iris , Shani Eilon , Weinstain Roy , Gaba Victor , Tam Yehudit , Lers Amnon , Eshel Dani
Published: September 2016

The potato tuber is a swollen underground stem that can sprout under dark conditions. Sprouting initiates in the tuber apical bud (AP), while lateral buds (LTs) are repressed by apical dominance (AD). Under conditions of lost AD, removal of tuber LTs showed that they partially inhibit AP growth only at the AD stage. Detached buds were inhibited by exogenous application of naphthaleneacetic acid (NAA), whereas 6-benzyladenine (6-BA) and gibberellic acid (GA 3 ) induced bud burst and elongation, respectively. NAA, applied after 6-BA or GA 3 , nullified the latters’ growth-stimulating effect in both the AP and LTs. GA 3 applied to the fifth-position LT was transported mainly to the tuber’s AP. GA 3 treatment also resulted in increased indole-3-acetic acid (IAA) concentration and cis-zeatin O-glucoside in the AP. In a tuber tissue strip that included two or three buds connected by the peripheral vascular system, treatment of a LT with GA 3 affected only the AP side of the strip, suggesting that the AP is the strongest sink for GA 3 , which induces its etiolated elongation. Dipping etiolated sprouts in labeled GA 3 showed specific accumulation of the signal in the AP. Transcriptome analysis of GA 3 ’s effect showed that genes related to the cell cycle, cell proliferation, and hormone transport are up-regulated in the AP as compared to the LT. Sink demand for metabolites is suggested to support AD in etiolated stem growth by inducing differential gene expression in the AP.
MutationalPatterns: comprehensive genome-wide analysis of mutational processes
Authors: Blokzijl Francis , Janssen Roel , van Boxtel Ruben , Cuppen Edwin
Published: September 2016

Base substitution catalogs represent historical records of mutational processes that have been active in a system. Such processes can be distinguished by typical characteristics, like mutation type, sequence context, transcriptional and replicative strand bias, and distribution throughout the genome. MutationalPatterns is an R/Bioconductor package that characterizes this broad range of mutational patterns and potential relations with (epi-)genomic features. Furthermore, it offers an efficient method to quantify the contribution of known mutational signatures. Such analyses can be used to determine whether certain DNA repair mechanisms are perturbed and to further characterize the processes underlying known mutational signatures.
Microclimate and radiant energy measurements using a novel device for natural resource monitoring
Authors: Thomas Taylor , Wolf Adam
Published: September 2016

A novel device for microclimate and radiant energy monitoring of natural resources was compared to known reference instruments and sensors to gauge relative performance under field conditions in Nebraska and New Jersey, USA during summer 2016. For all measurements tested, including air temperature, relative humidity, barometric pressure, four component net radiation, and photosynthetically active radiation, the device reported values near or within the accuracy limits as stated by the reference instrument / sensor manufacturer.
Towards comprehensive and quantitative proteomics for diagnosis and therapy of human disease
Authors: Cifani Paolo , Kentsis Alex
Published: September 2016

Abbreviations

DDA

Data Dependent Acquisition

DIA

Data Independent Acquisition

PRM

Parallel Reaction Monitoring

PTM

post-translational modification

SAX

strong anion exchange (chromatography)

SCX

Strong cation exchange (chromatography)

Despite superior analytical features, mass spectrometry proteomics remains seldom used for the basic investigation and clinical treatment of human disease. This need is particularly pressing for childhood diseases that can be rare in incidence and variable in presentation. Modern mass spectrometry enables detailed functional characterization of the pathogenic biochemical processes, as achieved by accurate and comprehensive quantification of proteins and their regulatory chemical modifications. Here, we describe how high-accuracy mass spectrometry in combination with high-resolution chromatographic separations can be leveraged to meet these analytical requirements in a mechanism-focused manner. We review the quantification methods capable of producing accurate measurements of protein abundance and post-translational modification stoichiometries. We then discuss how experimental design and chromatographic resolution can be leveraged to achieve comprehensive functional characterization of biochemical processes in complex biological proteomes. Finally, we describe current approaches for quantitative analysis of a common functional protein modification: reversible phosphorylation. In all, current instrumentation and methods of high-resolution chromatography and mass spectrometry proteomics are poised for immediate translation into improved diagnostic and therapeutic strategies for pediatric and adult diseases.
Cooperativity and modularity in protein folding
Authors: Sasai Masaki , Chikenji George , Terada Tomoki P.
Published: September 2016

A simple statistical mechanical model proposed by Wako and Saitô has explained the aspects of protein folding surprisingly well. This model was systematically applied to multiple proteins by Muñoz and Eaton and has since been referred to as the Wako-Saitô-Muñoz-Eaton (WSME) model. The success of the WSME model in explaining the folding of many proteins has verified the hypothesis that the folding is dominated by native interactions, which makes the energy landscape globally biased toward native conformation. Using the WSME and other related models, Saitô emphasized the importance of the hierarchical pathway in protein folding; folding starts with the creation of contiguous segments having a native-like configuration and proceeds as growth and coalescence of these segments. Theϕ-values calculated for barnase with the WSME model suggested that segments contributing to the folding nucleus are similar to the structural modules defined by the pattern of native atomic contacts. The WSME model was extended to explain folding of multi-domain proteins having a complex topology, which opened the way to comprehensively understanding the folding process of multi-domain proteins. The WSME model was also extended to describe allosteric transitions, indicating that the allosteric structural movement does not occur as a deterministic sequential change between two conformations but as a stochastic diffusive motion over the dynamically changing energy landscape. Statistical mechanical viewpoint on folding, as highlighted by the WSME model, has been renovated in the context of modern methods and ideas, and will continue to provide insights on equilibrium and dynamical features of proteins.
A new foreperiod effect on single-trial phase coherence. Part I: existence and relevance
Authors: Rapela Joaquin , Westerfield Marissa , Townsend Jeanne , Makeig Scott
Published: September 2016

Expecting events in time leads to more efficient behavior. A remarkable early finding in the study of temporal expectancy is the foreperiod effect on reaction times; i.e., the fact that the time period between a warning signal and an impendent stimuli, to which subjects are instructed to respond as quickly as possible, influences reaction times. Recently it has been shown that the phase of oscillatory activity preceding stimulus presentation is related to behavior. Here we connect both of these findings by reporting a novel foreperiod effect on the inter-trial phase coherence triggered by a stimulus to which subjects do not respond. Until now, inter-trial phase coherence has been used to describe a regularity in the phases of groups of trials. We propose a single-trial measure of inter-trial phase coherence and prove its soundness. Equipped with this measure, and using a multivariate decoding method, we demonstrate that the foreperiod duration modulates single-trial phase coherence. In principle, this modulation could be an artifact due to the decoding method used to detect it. We show that this is not the case, since the modulation can also be observed with a very simple averaging method. Although real, the single-trial modulation of inter-trial phase coherence by the foreperiod duration could just reflect a nuisance in our data. We argue against this possibility by showing that the strength of the modulation correlates with subjects’ behavioral measures, both error rates and mean-reaction times. We anticipate that the new foreperiod effect on inter-trial phase coherence, and the decoding method used here to detect it, will be important tools to understand cognition at the single-trial level. In Part II of this manuscript, we support this claim, by showing that attention modulates the strength of the new foreperiod effect in a trial-by-trial basis.
Primary Evidence of a Donut-Like, Fourth Spatial Dimension in the Brain
Authors: Peters James F. , İnan Ebubekir , Tozzi Arturo , Ramanna Sheela
Published: September 2016

We introduce a novel method for the measurement of information in fMRI neuroimages, i.e., nucleus clustering’s Rényi entropy derived from strong proximities in feature-based Voronoï tessellations, e.g., maximal nucleus clustering (MNC). We show how MNC is a novel, fast and inexpensive image-analysis technique, independent from the standard blood-oxygen-level dependent signals, which facilitates the objective detection of hidden temporal patterns of entropy/information in zones of fMRI images generally not taken into account by the subjective standpoint of the observer. In order to evaluate the potential applications of MNC, we looked for the presence of a fourth dimension’s distinctive hallmarks in a temporal sequence of 2D images taken during spontaneous brain activity. Indeed, recent findings suggest that several brain activities, such as mind-wandering and memory retrieval, might take place in the functional space of a four dimensional hypersphere, which is a double donut-like structure undetectable in the usual three dimensions. We found that the Rényi entropy is higher in MNC areas than in the surrounding ones, and that these temporal patterns closely resemble the trajectories predicted by the possible presence of a hypersphere in the brain.
Detecting consistent patterns of directional adaptation using differential selection codon models
Authors: Parto Sahar , Lartillot Nicolas
Published: September 2016

Background

Phylogenetic codon models are often used to characterize the selective regimes acting on protein coding sequences. Recent methodological developments have led to models explicitly accounting for the interplay between mutation and selection, by explicitly modelling the amino acid fitness landscape along the sequence. However, thus far, most of these models have assumed that the fitness landscape is constant over time. Fluctuations of the fitness landscape may often be random or depend on complex and unknown factors. However, some organisms may be subject to systematic changes in selective pressure, resulting in reproducible molecular adaptations across independent lineages subject to similar conditions.

Results

Here, we developed a codon-based differential selection model, which aims to detect and quantify the fine-grained consistent patterns of adaptation at the protein-coding level, as a function of external conditions experienced by the organism under investigation. The model parameterizes the global mutational pressure, as well as the site- and condition-specific amino acid selective preferences. This phylogenetic model is implemented in a Bayesian MCMC framework. After validation with simulations, we applied our method to a dataset of HIV sequences from patients with known HLA genetic background. Our differential selection model detects and characterizes differentially selected coding positions specifically associated with two different HLA alleles.

Conclusion

our differential selection model is able to identify consistent molecular adaptations as a function of repeated changes in the environment of the organism. These models can be applied to many other problems, ranging from viral adaptation to evolution of life-history strategies in plants or animals.
Functional Profiling Using the Saccharomyces Genome Deletion Project Collections
Authors: Nislow Corey , Wong Lai Hong , Lee Amy Huei-Yi , Giaever Guri
Published: September 2016

The ability to measure and quantify the fitness of an entire organism requires considerably more complex approaches than simply using traditional “omic” methods that examine, for example, the abundance of RNA transcripts, proteins, or metabolites. The yeast deletion collections represent the only systematic, comprehensive set of null alleles for any organism in which such fitness measurements can be assayed. Generated by the Saccharomyces Genome Deletion Project, these collections allow the systematic and parallel analysis of gene functions using any measurable phenotype. The unique 20-bp molecular barcodes engineered into the genome of each deletion strain facilitate the massively parallel analysis of individual fitness. Here, we present functional genomic protocols for use with the yeast deletion collections. We describe how to maintain, propagate, and store the deletion collections and how to perform growth fitness assays on single and parallel screening platforms. Phenotypic fitness analyses of the yeast mutants, described in brief here, provide important insights into biological functions, mechanisms of drug action, and response to environmental stresses. It is important to bear in mind that the specific assays described in this protocol represent some of the many ways in which these collections can be assayed, and in this description particular attention is paid to maximizing throughput using growth as the phenotypic measure.
Design and Generation of Drosophila Single Guide RNA Expression Constructs
Authors: Housden Benjamin E. , Hu Yanhui , Perrimon Norbert
Published: September 2016

The recent advances in CRISPR-based genome engineering have enabled a plethora of new experiments to study a wide range of biological questions. The major attraction of this system over previous methods is its high efficiency and simplicity of use. For example, whereas previous genome engineering technologies required the generation of new proteins to target each new locus, CRISPR requires only the expression of a different single guide RNA (sgRNA). This sgRNA binds to the Cas9 endonuclease protein and directs the generation of a double-strand break to a highly specific genomic site determined by the sgRNA sequence. In addition, the relative simplicity of the Drosophila genome is a particular advantage, as possible sgRNA off-target sites can easily be avoided. Here, we provide a step-by-step protocol for designing sgRNA target sites using the Drosophila RNAi Screening Center (DRSC) Find CRISPRs tool (version 2). We also describe the generation of sgRNA expression plasmids for the use in cultured Drosophila cells or in vivo. Finally, we discuss specific design requirements for various genome engineering applications.
Functional Genomics Using the Saccharomyces cerevisiae Yeast Deletion Collections
Authors: Nislow Corey , Wong Lai Hong , Lee Amy Huei-Yi , Giaever Guri
Published: September 2016

Constructed by a consortium of 16 laboratories, the Saccharomyces genome-wide deletion collections have, for the past decade, provided a powerful, rapid, and inexpensive approach for functional profiling of the yeast genome. Loss-of-function deletion mutants were systematically created using a polymerase chain reaction (PCR)-based gene deletion strategy to generate a start-to-stop codon replacement of each open reading frame by homologous recombination. Each strain carries two molecular barcodes that serve as unique strain identifiers, enabling their growth to be analyzed in parallel and the fitness contribution of each gene to be quantitatively assessed by hybridization to high-density oligonucleotide arrays or through the use of next-generation sequencing technologies. Functional profiling of the deletion collections, using either strain-by-strain or parallel assays, provides an unbiased approach to systematically survey the yeast genome. The Saccharomyces yeast deletion collections have proved immensely powerful in contributing to the understanding of gene function, including functional relationships between genes and genetic pathways in response to diverse genetic and environmental perturbations.
Analysis of the Schizosaccharomyces pombe Cell Cycle
Authors: Hagan Iain M. , Grallert Agnes , Simanis Viesturs
Published: September 2016

Schizosaccharomyces pombe cells are rod shaped, and they grow by tip elongation. Growth ceases during mitosis and cell division; therefore, the length of a septated cell is a direct measure of the timing of mitotic commitment, and the length of a wild-type cell is an indicator of its position in the cell cycle. A large number of documented stage-specific changes can be used as landmarks to characterize cell cycle progression under specific experimental conditions. Conditional mutations can permanently or transiently block the cell cycle at almost any stage. Large, synchronously dividing cell populations, essential for the biochemical analysis of cell cycle events, can be generated by induction synchrony (arrest-release of a cell cycle mutant) or selection synchrony (centrifugal elutriation or lactose-gradient centrifugation). Schizosaccharomyces pombe cell cycle studies routinely combine particular markers, mutants, and synchronization procedures to manipulate the cycle. We describe these techniques and list key landmarks in the fission yeast mitotic cell division cycle.
US-SOMO HPLC-SAXS module: dealing with capillary fouling and extraction of pure component patterns from poorly resolved SEC-SAXS data
Authors: Brookes Emre , Vachette Patrice , Rocco Mattia , Pérez Javier
Published: September 2016

Size-exclusion chromatography coupled with SAXS (small-angle X-ray scattering), often performed using a flow-through capillary, should allow direct collection of monodisperse sample data. However, capillary fouling issues and non-baseline-resolved peaks can hamper its efficacy. The UltraScan solution modeler (US-SOMO) HPLC-SAXS (high-performance liquid chromatography coupled with SAXS) module provides a comprehensive framework to analyze such data, starting with a simple linear baseline correction and symmetrical Gaussian decomposition tools [Brookes, Pérez, Cardinali, Profumo, Vachette & Rocco (2013). J. Appl. Cryst.
46, 1823–1833]. In addition to several new features, substantial improvements to both routines have now been implemented, comprising the evaluation of outcomes by advanced statistical tools. The novel integral baseline-correction procedure is based on the more sound assumption that the effect of capillary fouling on scattering increases monotonically with the intensity scattered by the material within the X-ray beam. Overlapping peaks, often skewed because of sample interaction with the column matrix, can now be accurately decomposed using non-symmetrical modified Gaussian functions. As an example, the case of a polydisperse solution of aldolase is analyzed: from heavily convoluted peaks, individual SAXS profiles of tetramers, octamers and dodecamers are extracted and reliably modeled.
Swedish military officers through other nations’ eyes
Authors: Larsson Gerry , Brandow Carina , Fors Brandebo Maria , Ohlsson Alicia , Åselius Gunnar
Published: August 2016

Purpose

Globalisation of working life means that many organisations are manned by people from different countries. A potentially critical factor is how members from various nations are looked upon by their partner countries. Such perception may be more or less accurate and affect organisational outcomes. The military is no exception as modern warfare is characterised by multinational composition of task forces. The aim of this paper was to gain a deeper understanding of how military officers from other nations perceive Swedish military officers and their leadership qualities in particular.

Design/methodology/approach

Interviews were conducted with 20 military officers representing ten nations. Interview questions were deduced from the Developmental leadership model. Responses were first coded inductively according to the constant comparative method. Generated categories were then deductively related to this leadership model.

Findings

The analysis resulted in positive and negative patterns. The positive picture included Swedish officers being perceived as calm, competent and generally good at exhibiting exemplary leadership behaviour, showing individualised consideration and creating an inspiring atmosphere. The negative side included opinions such as Swedish officers being too emotionally restrained, exhibiting poor self-confidence, discussing too much before making decisions and having difficulties giving negative feedback. The results are discussed in relation to the Developmental leadership model and the stereotype concept.

Research limitations/implications

Small sample size and a focus on military organisations imply a low degree of generalisability.

Practical implications

Three suggestions regarding Swedish officer education are presented: officer students should be given an increased awareness of how they are perceived by others, decision-making without group support and giving negative feedback in a constructive, straight forward, but still considerate way, should be practiced and more attention should be paid to emotion management.

Originality/value

The paper addresses an increasing tendency in work organisations – a multinational composition of the work force. The foundation of study in leadership theory and the stereotype concept is new.
Transition from conventional to light‐emitting diode street lighting changes activity of urban bats
Authors: Lewanzik Daniel , Voigt Christian C.
Published: September 2016

Light pollution is rapidly increasing and can have deleterious effects on biodiversity, yet light types differ in their effect on wildlife. Among the light types used for street lamps, light‐emitting diodes (LEDs) are expected to become globally predominant within the next few years.

In a large‐scale field experiment, we recorded bat activity at 46 street lights for 12 nights each and investigated how the widespread replacement of conventional illuminants by LEDs affects urban bats: we compared bat activity at municipal mercury vapour (MV) street lamps that were replaced by LEDs with control sites that were not changed.

Pipistrellus pipistrellus was the most frequently recorded species; it was 45% less active at LEDs than at MV street lamps, but the activity did not depend on illuminance level. Light type did not affect the activity of Pipistrellus nathusii, Pipistrellus pygmaeus or bats in the Nyctalus/Eptesicus/Vespertilio (NEV) group, yet the activity of P. nathusii increased with illuminance level. Bats of the genus Myotis increased activity 4·5‐fold at LEDs compared with MV lights, but illuminance level had no effect.

Decreased activity of P. pipistrellus, which are considered light tolerant, probably paralleled insect densities around lights. Further, our results suggest that LEDs may be less repelling for light‐averse Myotis spp. than MV lights. Accordingly, the transition from conventional lighting techniques to LEDs may greatly alter the anthropogenic impact of artificial light on urban bats and might eventually affect the resilience of urban bat populations.

Synthesis and applications. At light‐emitting diodes (LEDs), the competitive advantage – the exclusive ability to forage on insect aggregations at lights – is reduced for light‐tolerant bats. Thus, the global spread of LED street lamps might lead to a more natural level of competition between light‐tolerant and light‐averse bats. This effect could be reinforced if the potential advantages of LEDs over conventional illuminants are applied in practice: choice of spectra with relatively little energy in the short wavelength range; reduced spillover by precisely directing light; dimming during low human activity times; and control by motion sensors. Yet, the potential benefits of LEDs could be negated if low costs foster an overall increase in artificial lighting.
Educational Achievement and the Allocation of School Resources
Authors: Cobb‐Clark Deborah A. , Jha Nikhil
Published: September 2016

The debate on school resources and educational outcomes has focused almost exclusively on spending levels. We extend this by analysing the relationship between student achievement and schools' budget allocations using panel data. Per‐pupil expenditure has no apparent link to improvement in students' standardised test scores. However, the allocation of the budget matters for student achievement in some grades. Ancillary teaching staff are linked to faster growth in numeracy and literacy in primary‐ and middle‐schools. Spending on experienced teachers is also important for writing achievement in the primary‐school years. On the whole, we find very little evidence of inefficient spending patterns.
Bayesian Vector Autoregressions
Authors: Woźniak Tomasz
Published: September 2016

This article provides an introduction to the burgeoning academic literature on Bayesian vector autoregressions, benchmark models for applied macroeconomic research. I first explain Bayes’ theorem and the derivation of the closed‐form solution for the posterior distribution of the parameters of the model's given data. I further consider parameter shrinkage, a distinguishing feature of the prior distributions commonly employed in the analysis of large data. Finally, I describe the mechanisms that enable feasible computations for these linear models that efficiently extract the information content of many variables for economic forecasting and other applications.
Badges of Modern Slavery
Authors: Paz‐Fuchs Amir
Published: September 2016

Notwithstanding the 19th century formal abolition of slavery as legal ownership of people, modern slavery and forced labour have not been consigned to the past. In fact, their existence is more widespread, and made more difficult to tackle due to the lack of formal, legal criteria. This article suggests that reference to historical institutions reveals seven ‘badges of slavery’ that are helpful in identifying occurrences of modern slavery and forced labour. These are: humiliation, ownership of people, exploitation of the vulnerable, lack of consent, terms and conditions of employment, limits on the power to end the employment relationship, and denial of rights outside the work relationship. These constitute modern slavery, and distinguish it from other instances of exploitative employment relations, however problematic. In addition, even where the label of modern slavery is misplaced, the identification of particular badges of slavery in contemporary employment relations may assist in highlighting their troubling facets.
Judges and Politics: The Parliamentary Contributions of the Law Lords 1876–2009
Authors: O'Brien Patrick
Published: September 2016

There is a common perception that, prior to the exclusion of serving judges from the House of Lords in 2009, a ‘politics convention’ operated which required judges to avoid party‐political controversy and ensured that they contributed to debate only rarely. On this view, the presence of the Law Lords in parliament prior to 2009 presented a judicial independence and separation of powers problem in theory only. An examination of the contributions of serving Law Lords and other judicial peers to debates in the House of Lords from 1876–2009 (and retired judges from 1876–2015) reveals that the convention either did not exist or was frequently ignored. While most judges were infrequent participants in parliamentary debate, some were enthusiastic – a small number among the most active parliamentarians in the Lords. The most active judicial peers were conservative in their politics and the best predictor that a judge would be active in the House was an association with conservative politics or causes.
Interdiction and Indoctrination: The Counter‐Terrorism and Security Act 2015
Authors: Blackbourn Jessie , Walker Clive
Published: September 2016

Lying behind the recent Counter‐Terrorism and Security Act 2015 is the phenomenon of foreign terrorist fighters which has sparked international and national attention. The 2015 Act deals with many facets of counter terrorism legislation, but its two principal measures are singled out for analysis and critique in this paper. Thus, Part I of the Act seeks to interdict foreign terrorist fighters by preventing suspects from travelling and dealing decisively with those already in the UK who pose a risk. Part V of the Act implements the second, broader aspect, of legislative policy, reflecting the UN emphasis on ‘Countering Violent Extremism’, through the statutory elaboration and enforcement of the ‘Prevent’ element of the long‐established Countering International Terrorism strategy, which aims to stop people becoming terrorists or supporting violent extremism. These measures are explained in their policy contexts and set against criteria of effectiveness, personal freedom, and accountability.
Vicarious Liability and Non‐Delegable Duty for Child Abuse in Foster Care: A Step Too Far?
Authors: Tofaris Stelios
Published: September 2016

In NA v Nottinghamshire County Council the Court of Appeal held that a local authority is not liable under vicarious liability or for breach of a non‐delegable duty when foster parents sexually or physically abuse a child that it has placed in their care. The note discusses the decision in the light of recent developments in the law. It is argued that the result is unsatisfactory in terms of doctrine and policy. It is further suggested that non‐delegable duty, rather than vicarious liability, offers the most appropriate route for establishing liability.
Challenges in addressing professional competence expectations in human resource management courses
Authors: Coetzer Alan , Ryan Maria M , Susomrith Pattanee , Suseno Yuliani
Published: September 2016

Although research has identified many of the competences that human resource management (HRM) professionals need, limited research examines how competence expectations can be met in HRM courses. This study sought to generate the knowledge required to align HRM courses with competence statements in the recently revised Australian Human Resources Institute Model of Excellence. To accomplish this aim, focus groups and interviews were conducted with HRM professionals from private, public and not‐for‐profit organisations. Findings suggest that the process of aligning course curricula with the MoE is challenging for several reasons, including: competence statements are subject to varied interpretation; subjecting each statement to a learning needs analysis is complex; it is difficult to cluster the wide range of knowledge areas that must be covered into coherent units of learning. This paper explores the appropriateness of using a generic competence model in a curricular‐influencing role and outlines implications of our findings for practice and research.
Possible Mechanisms of Ethanol‐Mediated Colorectal Carcinogenesis: The Role of Cytochrome P4502E1, Etheno‐DNA Adducts, and the Anti‐Apoptotic Protein Mcl‐1
Authors: Koehler Bruno Christian , Arslic‐Schmitt Tatjana , Peccerella Theresa , Scherr Anna‐Lena , Schulze‐Bergkamen Henning , Bruckner Thomas , Gdynia Georg , Jäger Dirk , Mueller Sebastian , Bartsch Helmut , Seitz Helmut K.
Published: September 2016

Background

Chronic alcohol consumption is a risk factor for colorectal cancer. The mechanisms by which ethanol (EtOH) exerts its carcinogenic effect on the colorectal mucosa are not clear and may include oxidative stress with the action of reactive oxygen species (ROS) generated through EtOH metabolism via cytochrome P4502E1 (CYP2E1) leading to carcinogenic etheno‐DNA adducts. ROS may also induce apoptosis. However, the effect of chronic EtOH consumption on CYP2E1, etheno‐DNA adducts as well as anti‐apoptotic proteins in the colorectal mucosa of heavy drinkers without colorectal inflammation is still not known.

Methods

Rectal biopsies from 32 alcoholics (>60 g EtOH/d) and from 12 controls (<20 g EtOH/d) were histologically examined, and immunohistochemistry for CYP2E1 and etheno‐DNA adducts was performed. Apoptosis (cleaved PARP) as well as anti‐apoptotic proteins including Bcl‐xL, Bcl‐2, and Mcl‐1 were immunohistochemically determined.

Results

No significant difference in mucosal CYP2E1 or etheno‐DNA adducts was observed between alcoholics and control patients. However, CYP2E1 and etheno‐DNA adducts correlated significantly when both groups were combined (p < 0.001). In addition, although apoptosis was found not to be significantly affected by EtOH, the anti‐apoptotic protein Mcl‐1, but neither Bcl‐xL nor Bcl‐2, was found to be significantly increased in heavy drinkers as compared to controls (p = 0.014).

Conclusions

Although colorectal CYP2E1 was not found to be significantly increased in alcoholics, CYP2E1 correlated overall with the level of etheno‐DNA adducts in the colorectal mucosa, which identifies CYP2E1 as an important factor in colorectal carcinogenesis. Most importantly, however, is the up‐regulation of the anti‐apoptotic protein Mcl‐1 in heavy drinkers counteracting apoptosis and possibly stimulating cancer development.