bluuebunny/crossref_metadata_2025 huggingface dataset:
Rethinking Legal Services in the Face of Globalization and Technology Innovation: The Case of Radiant Law
Authors: Lacity Mary C , Willcocks Leslie
Published: February 2016

In this teaching case, we challenge students to think about and discuss how the legal profession can adapt to disruptive forces caused by the globalization of skills and technology innovation. The case focuses on how one UK-based firm – Radiant Law – completely rethought the delivery of legal services. This ‘new age’ law firm continually tested the boundaries of new ways to leverage the value of global talent and technology. For example, it changed its pricing and sourcing models, adopted new technologies, hired freelance IT professionals globally to develop software to streamline its legal work, engaged outsourcing providers in India and (subsequently) in South Africa. After nearly 3 years in South Africa, Radiant Law contemplated switching its sourcing model again. The Radiant Law story supports discussion about challenges associated with global sourcing decisions and the present and future shape of professional work and services in an increasingly technology-enabled, globalized world.
Case study: Renewable electricity generation systems on Geoje Island in South Korea
Authors: Park Eunil , Yoo Kyeongsik , Ohm Jay Y. , Kwon Sang Jib
Published: February 2016

Since the concept of “green growth” has become a main growth strategy for South Korea, the South Korean Government has consistently invested in the distribution and installation of renewable power generation systems, such as recommending that island communities install renewable power generation systems to reduce the cost of maintaining and operating the electricity grid system linking the islands to the mainland. Given the South Korean energy industry's heavy dependence on nuclear and fossil fuels, such renewable power generation systems are advised for both mainland and island communities. Therefore, the current study uses the Hybrid Optimization of Multiple Energy Resources (HOMER) program software to explore possible solutions to the installation and operation of independent and renewable electricity generation systems on Geoje Island, the second largest island in South Korea. The results show that photovoltaic panels, batteries, wind turbines, and converters can be used to organize such a system on Geoje Island. This study presents an optimized electricity generation system in the context of the total net present cost, fraction of renewables, and cost of energy (COE). The suggested system presents a 1.00 fraction of renewables at a COE of $0.472 per kW h. Implications, limitations, and future research areas are presented.
On device design for steep-slope negative-capacitance field-effect-transistor operating at sub-0.2V supply voltage with ferroelectric HfO2 thin film
Authors: Kobayashi Masaharu , Hiramoto Toshiro
Published: February 2016

Internet-of-Things (IoT) technologies require a new energy-efficient transistor which operates at ultralow voltage and ultralow power for sensor node devices employing energy-harvesting techniques as power supply. In this paper, a practical device design guideline for low voltage operation of steep-slope negative-capacitance field-effect-transistors (NCFETs) operating at sub-0.2V supply voltage is investigated regarding operation speed, material requirement and energy efficiency in the case of ferroelectric HfO2 gate insulator, which is the material fully compatible to Complementary Metal-Oxide-Semiconductor (CMOS) process technologies. A physics-based numerical simulator was built to design NCFETs with the use of experimental HfO2 material parameters by modeling the ferroelectric gate insulator and FET channel simultaneously. The simulator revealed that NCFETs with ferroelectric HfO2 gate insulator enable hysteresis-free operation by setting appropriate operation point with a few nm thick gate insulator. It also revealed that, if the finite response time of spontaneous polarization of the ferroelectric gate insulator is 10-100psec, 1-10MHz operation speed can be achieved with negligible hysteresis. Finally, by optimizing material parameters and tuning negative capacitance, 2.5 times higher energy efficiency can be achieved by NCFET than by conventional MOSFETs. Thus, NCFET is expected to be a new CMOS technology platform for ultralow power IoT.
Qualitative insight and quantitative analysis of the effect of temperature on the coercivity of a magnetic system
Authors: Moskalenko Mariia , Bessarab Pavel F. , Uzdin Valery M. , Jónsson Hannes
Published: February 2016

The temperature dependence of the response of a magnetic system to an applied field can be understood qualitatively by considering variations in the energy surface characterizing the system and estimated quantitatively with rate theory. In the system analysed here, Fe/Sm-Co spring magnet, the width of the hysteresis loop is reduced to a half when temperature is raised from 25 K to 300 K. This narrowing can be explained and reproduced quantitatively without invoking temperature dependence of model parameters as has typically been done in previous data analysis. The applied magnetic field lowers the energy barrier for reorientation of the magnetization but thermal activation brings the system over the barrier. A 2-dimensional representation of the energy surface is developed and used to gain insight into the transition mechanism and to demonstrate how the applied field alters the transition path. Our results show the importance of explicitly including the effect of thermal activation when interpreting experiments involving the manipulation of magnetic systems at finite temperature.
Observation of nuclear gamma resonance with superconducting tunnel junction detectors
Authors: Kozin M. G. , Romashkina I. L. , Filippenko L. V. , Koshelets V. P.
Published: February 2016

Nb-based superconducting tunnel junction detectors have been used for the registration of electrons following a nuclear gamma resonance (Mössbauer effect). Electrons were produced by a RhFe scatterer under irradiation by the 57Co(Rh) Mössbauer source. This observation demonstrates the role which can be played by superconducting tunnel junction detectors in the field of conversion electron Mössbauer spectroscopy and other types of electron spectroscopy.
Verbal social primes alter motor contagion during action observation
Authors: Sparks S. , Douglas T. , Kritikos A.
Published: February 2016

We investigated whether prosocial and nonsocial word primes prior to action observation modify subsequent initiation and execution of the observer's own reach-to-grasp actions. Participants observed a model performing exaggeratedly curved (vertical deviation) or natural straight reaches to a vertical dowel and always performed a straight reach to a dowel themselves. Observing curved movements slowed initiation times and increased the vertical deviation of the participants’ movements. Observing curved movements enhanced vertical deviation only in the prosocial word primes condition. We suggest that social context priming can modulate initiation of movement as well as the extent of motor contagion (in this case, the extent of vertical deviation) between model and observer.
Integration of string and de Bruijn graphs for genome assembly
Authors: Huang Yao-Ting , Liao Chen-Fu
Published: February 2016

Motivation: String and de Bruijn graphs are two graph models used by most genome assemblers. At present, none of the existing assemblers clearly outperforms the others across all datasets. We found that although a string graph can make use of entire reads for resolving repeats, de Bruijn graphs can naturally assemble through regions that are error-prone due to sequencing bias.

Results: We developed a novel assembler called StriDe that has advantages of both string and de Bruijn graphs. First, the reads are decomposed adaptively only in error-prone regions. Second, each paired-end read is extended into a long read directly using an FM-index. The decomposed and extended reads are used to build an assembly graph. In addition, several essential components of an assembler were designed or improved. The resulting assembler was fully parallelized, tested and compared with state-of-the-art assemblers using benchmark datasets. The results indicate that contiguity of StriDe is comparable with top assemblers on both short-read and long-read datasets, and the assembly accuracy is high in comparison with the others.

Availability and implementation:  https://github.com/ythuang0522/StriDe

Contact: ythuang@cs.ccu.edu.tw

Supplementary information:  Supplementary data are available at Bioinformatics online.
TRONCO: an R package for the inference of cancer progression models from heterogeneous genomic data
Authors: De Sano Luca , Caravagna Giulio , Ramazzotti Daniele , Graudenzi Alex , Mauri Giancarlo , Mishra Bud , Antoniotti Marco
Published: February 2016

Motivation: We introduce TRanslational ONCOlogy (TRONCO), an open-source R package that implements the state-of-the-art algorithms for the inference of cancer progression models from (epi)genomic mutational profiles. TRONCO can be used to extract population-level models describing the trends of accumulation of alterations in a cohort of cross-sectional samples, e.g. retrieved from publicly available databases, and individual-level models that reveal the clonal evolutionary history in single cancer patients, when multiple samples, e.g. multiple biopsies or single-cell sequencing data, are available. The resulting models can provide key hints for uncovering the evolutionary trajectories of cancer, especially for precision medicine or personalized therapy.

Availability and implementation: TRONCO is released under the GPL license, is hosted at http://bimib.disco.unimib.it/ (Software section) and archived also at bioconductor.org.

Contact:  tronco@disco.unimib.it

Supplementary information:  Supplementary data are available at Bioinformatics online.
ParDRe: faster parallel duplicated reads removal tool for sequencing studies
Authors: González-Domínguez Jorge , Schmidt Bertil
Published: February 2016

Summary: Current next generation sequencing technologies often generate duplicated or near-duplicated reads that (depending on the application scenario) do not provide any interesting biological information but can increase memory requirements and computational time of downstream analysis. In this work we present ParDRe, a de novo parallel tool to remove duplicated and near-duplicated reads through the clustering of Single-End or Paired-End sequences from fasta or fastq files. It uses a novel bitwise approach to compare the suffixes of DNA strings and employs hybrid MPI/multithreading to reduce runtime on multicore systems. We show that ParDRe is up to 27.29 times faster than Fulcrum (a representative state-of-the-art tool) on a platform with two 8-core Sandy-Bridge processors.

Availability and implementation: Source code in C ++ and MPI running on Linux systems as well as a reference manual are available at https://sourceforge.net/projects/pardre/

Contact:  jgonzalezd@udc.es
A zero-inflated Poisson model for insertion tolerance analysis of genes based on Tn-seq data
Authors: Liu Fangfang , Wang Chong , Wu Zuowei , Zhang Qijing , Liu Peng
Published: February 2016

Motivation: Transposon insertion sequencing (Tn-seq) is an emerging technology that combines transposon mutagenesis with next-generation sequencing technologies for the identification of genes related to bacterial survival. The resulting data from Tn-seq experiments consist of sequence reads mapped to millions of potential transposon insertion sites and a large portion of insertion sites have zero mapped reads. Novel statistical method for Tn-seq data analysis is needed to infer functions of genes on bacterial growth.

Results: In this article, we propose a zero-inflated Poisson model for analyzing the Tn-seq data that are high-dimensional and with an excess of zeros. Maximum likelihood estimates of model parameters are obtained using an expectation–maximization (EM) algorithm, and pseudogenes are utilized to construct appropriate statistical tests for the transposon insertion tolerance of normal genes of interest. We propose a multiple testing procedure that categorizes genes into each of the three states, hypo-tolerant, tolerant and hyper-tolerant, while controlling the false discovery rate. We evaluate the proposed method with simulation studies and apply the proposed method to a real Tn-seq data from an experiment that studied the bacterial pathogen, Campylobacter jejuni.

Availability and implementation: We provide R code for implementing our proposed method at http://github.com/ffliu/TnSeq. A user’s guide with example data analysis is also available there.

Contact: pliu@iastate.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
RVTESTS: an efficient and comprehensive tool for rare variant association analysis using sequence data
Authors: Zhan Xiaowei , Hu Youna , Li Bingshan , Abecasis Goncalo R. , Liu Dajiang J.
Published: February 2016

Motivation: Next-generation sequencing technologies have enabled the large-scale assessment of the impact of rare and low-frequency genetic variants for complex human diseases. Gene-level association tests are often performed to analyze rare variants, where multiple rare variants in a gene region are analyzed jointly. Applying gene-level association tests to analyze sequence data often requires integrating multiple heterogeneous sources of information (e.g. annotations, functional prediction scores, allele frequencies, genotypes and phenotypes) to determine the optimal analysis unit and prioritize causal variants. Given the complexity and scale of current sequence datasets and bioinformatics databases, there is a compelling need for more efficient software tools to facilitate these analyses. To answer this challenge, we developed RVTESTS, which implements a broad set of rare variant association statistics and supports the analysis of autosomal and X-linked variants for both unrelated and related individuals. RVTESTS also provides useful companion features for annotating sequence variants, integrating bioinformatics databases, performing data quality control and sample selection. We illustrate the advantages of RVTESTS in functionality and efficiency using the 1000 Genomes Project data.

Availability and implementation: RVTESTS is available on Linux, MacOS and Windows. Source code and executable files can be obtained at https://github.com/zhanxw/rvtests

Contact:  zhanxw@gmail.com; goncalo@umich.edu; dajiang.liu@outlook.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
solarius: an R interface to SOLAR for variance component analysis in pedigrees
Authors: Ziyatdinov Andrey , Brunel Helena , Martinez-Perez Angel , Buil Alfonso , Perera Alexandre , Soria Jose Manuel
Published: February 2016

Summary: The open source environment R is one of the most widely used software for statistical computing. It provides a variety of applications including statistical genetics. Most of the powerful tools for quantitative genetic analyses are stand-alone free programs developed by researchers in academia. SOLAR is one of the standard software programs to perform linkage and association mappings of the quantitative trait loci (QTLs) in pedigrees of arbitrary size and complexity. solarius allows the user to exploit the variance component methods implemented in SOLAR. It automates such routine operations as formatting pedigree and phenotype data. It parses also the model output and contains summary and plotting functions for exploration of the results. In addition, solarius enables parallel computing of the linkage and association analyses that makes the calculation of genome-wide scans more efficient.

Availability and implementation: solarius is available on CRAN and on GitHub https://github.com/ugcd/solarius.

Contact: aziyatdinov@santpau.cat
Empirical evidence for different cognitive effects in explaining the attribution of marine range shifts to climate change
Authors: van Putten Ingrid E. , Frusher Stewart , Fulton Elizabeth A. , Hobday Alistair J. , Jennings Sarah M. , Metcalf Sarah , Pecl Gretta T. ,   Handling editor: Sarah Kraak
Published: February 2016

The changing geographical distribution of species, or range shift, is one of the better documented fingerprints of climate change in the marine environment. Range shifts may also lead to dramatic changes in the distribution of economic, social, and cultural opportunities. These challenge marine resource users' capacity to adapt to a changing climate and managers' ability to implement adaptation plans. In particular, a reluctance to attribute marine range shift to climate change can undermine the effectiveness of climate change communications and pose a potential barrier to successful adaptation. Attribution is a known powerful predictor of behavioural intention. Understanding the cognitive processes that underpin the formation of marine resource users' beliefs about the cause of observed marine range shift phenomena is therefore an important topic for research. An examination of the attribution by marine resource users of three types of range shifts experienced in a marine climate change hotspot in southeast Australia to various climate and non-climate drivers indicates the existence of at least three contributing cognitions. These are: (i) engrained mental representations of environmental phenomena, (ii) scientific complexity in the attribution pathway, and (iii) dissonance from the positive or negative nature of the impact. All three play a part in explaining the complex pattern of attribution of marine climate change range shifts, and should be considered when planning for engagement with stakeholders and managers around adaptation to climate change.
FRB repetition and non-Poissonian statistics
Authors: Connor Liam , Pen Ue-Li , Oppermann Niels
Published: February 2016

We discuss some of the claims that have been made regarding the statistics of fast radio bursts (FRBs). In an earlier Letter, we conjectured that flicker noise associated with FRB repetition could show up in non-cataclysmic neutron star emission models, like supergiant pulses. We show how the current limits of repetition would be significantly weakened if their repeat rate really were non-Poissonian and had a pink or red spectrum. Repetition and its statistics have implications for observing strategy, generally favouring shallow wide-field surveys, since in the non-repeating scenario survey depth is unimportant. We also discuss the statistics of the apparent latitudinal dependence of FRBs, and offer a simple method for calculating the significance of this effect. We provide a generalized Bayesian framework for addressing this problem, which allows for direct model comparison. It is shown how the evidence for a steep latitudinal gradient of the FRB rate is less strong than initially suggested and simple explanations like increased scattering and sky temperature in the plane are sufficient to decrease the low-latitude burst rate, given current data. The reported dearth of bursts near the plane is further complicated if FRBs have non-Poissonian repetition, since in that case the event rate inferred from observation depends on observing strategy.
Lessons from sea louse and salmon epidemiology
Authors: Groner Maya L. , Rogers Luke A. , Bateman Andrew W. , Connors Brendan M. , Frazer L. Neil , Godwin Sean C. , Krkošek Martin , Lewis Mark A. , Peacock Stephanie J. , Rees Erin E. , Revie Crawford W. , Schlägel Ulrike E.
Published: February 2016

Effective disease management can benefit from mathematical models that identify drivers of epidemiological change and guide decision-making. This is well illustrated in the host–parasite system of sea lice and salmon, which has been modelled extensively due to the economic costs associated with sea louse infections on salmon farms and the conservation concerns associated with sea louse infections on wild salmon. Consequently, a rich modelling literature devoted to sea louse and salmon epidemiology has been developed. We provide a synthesis of the mathematical and statistical models that have been used to study the epidemiology of sea lice and salmon. These studies span both conceptual and tactical models to quantify the effects of infections on host populations and communities, describe and predict patterns of transmission and dispersal, and guide evidence-based management of wild and farmed salmon. As aquaculture production continues to increase, advances made in modelling sea louse and salmon epidemiology should inform the sustainable management of marine resources.
Infectious diseases of marine molluscs and host responses as revealed by genomic tools
Authors: Guo Ximing , Ford Susan E.
Published: February 2016

More and more infectious diseases affect marine molluscs. Some diseases have impacted commercial species including MSX and Dermo of the eastern oyster, QPX of hard clams, withering syndrome of abalone and ostreid herpesvirus 1 (OsHV-1) infections of many molluscs. Although the exact transmission mechanisms are not well understood, human activities and associated environmental changes often correlate with increased disease prevalence. For instance, hatcheries and large-scale aquaculture create high host densities, which, along with increasing ocean temperature, might have contributed to OsHV-1 epizootics in scallops and oysters. A key to understanding linkages between the environment and disease is to understand how the environment affects the host immune system. Although we might be tempted to downplay the role of immunity in invertebrates, recent advances in genomics have provided insights into host and parasite genomes and revealed surprisingly sophisticated innate immune systems in molluscs. All major innate immune pathways are found in molluscs with many immune receptors, regulators and effectors expanded. The expanded gene families provide great diversity and complexity in innate immune response, which may be key to mollusc's defence against diverse pathogens in the absence of adaptive immunity. Further advances in host and parasite genomics should improve our understanding of genetic variation in parasite virulence and host disease resistance.
Reserves as tools for alleviating impacts of marine disease
Authors: Lamb Joleah B. , Wenger Amelia S. , Devlin Michelle J. , Ceccarelli Daniela M. , Williamson David H. , Willis Bette L.
Published: February 2016

Marine protected areas can prevent over-exploitation, but their effect on marine diseases is less clear. We examined how marine reserves can reduce diseases affecting reef-building corals following acute and chronic disturbances. One year after a severe tropical cyclone, corals inside reserves had sevenfold lower levels of disease than those in non-reserves. Similarly, disease prevalence was threefold lower on reserve reefs following chronic exposure to terrestrial run-off from a degraded river catchment, when exposure duration was below the long-term site average. Examination of 35 predictor variables indicated that lower levels of derelict fishing line and injured corals inside reserves were correlated with lower levels of coral disease in both case studies, signifying that successful disease mitigation occurs when activities that damage reefs are restricted. Conversely, reserves were ineffective in moderating disease when sites were exposed to higher than average levels of run-off, demonstrating that reductions in water quality undermine resilience afforded by reserve protection. In addition to implementing protected areas, we highlight that disease management efforts should also target improving water quality and limiting anthropogenic activities that cause injury.
Ochre star mortality during the 2014 wasting disease epizootic: role of population size structure and temperature
Authors: Eisenlord Morgan E. , Groner Maya L. , Yoshioka Reyn M. , Elliott Joel , Maynard Jeffrey , Fradkin Steven , Turner Margaret , Pyne Katie , Rivlin Natalie , van Hooidonk Ruben , Harvell C. Drew
Published: February 2016

Over 20 species of asteroids were devastated by a sea star wasting disease (SSWD) epizootic, linked to a densovirus, from Mexico to Alaska in 2013 and 2014. ForPisaster ochraceusfrom the San Juan Islands, South Puget Sound and Washington outer coast, time-series monitoring showed rapid disease spread, high mortality rates in 2014, and continuing levels of wasting in the survivors in 2015. Peak prevalence of disease at 16 sites ranged to 100%, with an overall mean of 61%. Analysis of longitudinal data showed disease risk was correlated with both size and temperature and resulted in shifts in population size structure; adult populations fell to one quarter of pre-outbreak abundances. In laboratory experiments, time between development of disease signs and death was influenced by temperature in adults but not juveniles and adult mortality was 18% higher in the 19°C treatment compared to the lower temperature treatments. While larger ochre stars developed disease signs sooner than juveniles, diseased juveniles died more quickly than diseased adults. Unusual 2–3°C warm temperature anomalies were coincident with the summer 2014 mortalities. We suggest these warm waters could have increased the disease progression and mortality rates of SSWD in Washington State.
Genome-wide histone modification patterns inKluyveromyces Lactisreveal evolutionary adaptation of a heterochromatin-associated mark
Authors: Bean Angela , Weiner Assaf , Hughes Amanda , Itskovits Eyal , Friedman Nir , Rando Oliver J.
Published: February 2016

The packaging of eukaryotic genomes into nucleosomes plays critical roles in all DNA-templated processes, and chromatin structure has been implicated as a key factor in the evolution of gene regulatory programs. While the functions of many histone modifications appear to be highly conserved throughout evolution, some well-studied modifications such as H3K9 and H3K27 methylation are not found in major model organisms such asSaccharomyces cerevisiae, while other modifications gain/lose regulatory functions during evolution. To study such a transition we focused on H3K9 methylation, a heterochromatin mark found in metazoans and in the fission yeastS. pombe, but which has been lost in the lineage leading to the model budding yeastS. cerevisiae. We show that this mark is present in the relatively understudied yeastKluyveromyces lactis, a Hemiascomycete that diverged fromS. cerevisiaeprior to the whole-genome duplication event that played a key role in the evolution of a primarily fermentative lifestyle. We mapped genome-wide patterns of H3K9 methylation as well as several conserved modifications. We find that well-studied modifications such as H3K4me3, H3K36me3, and H3S10ph exhibit generally conserved localization patterns. Interestingly, we show H3K9 methylation inK. lactisprimarily occurs over highly-transcribed regions, including both Pol2 and Pol3 transcription units. We identified the H3K9 methylase as the ortholog ofSet6, whose function inS. cerevisiaeis obscure. Functionally, we show that deletion ofKlSet6does not affect highly H3K9me3-marked genes, providing another example of a major disconnect between histone mark localization and function. Together, these results shed light on surprising plasticity in the function of a widespread chromatin mark.
A tradeoff between the ecological and evolutionary stabilities of public goods genes in microbial populations
Authors: Rauch Joseph , Kondev Jane , Sanchez Alvaro
Published: February 2016

Microbial populations often rely on the cooperative production of extracellular “public goods” molecules. The cooperative nature of public good production may lead to minimum viable population sizes, below which populations collapse. In addition, “cooperator” public goods producing cells face evolutionary competition from non-producing mutants, or “freeloaders”. Thus, public goods cooperators have to be stable not only to the invasion of freeloaders, but also to ecological perturbations that may push their numbers too small to be sustainable. Through a combination of experiments with microbial populations and mathematical analysis of the Ecological Public Goods Game, we show that game parameters and experimental conditions that improve the evolutionary stability of cooperators also lead to a low ecological stability of the cooperator population. Complex regulatory strategies mimicking those used by microbes in nature may allow cooperators to beat this eco-evolutionary stability tradeoff and become resistant to freeloaders while at the same time maximizing their ecological stability. Our results thus identify the coupled eco-evolutionary stability as being key for the long-term viability of microbial public goods cooperators.
Bipartite recognition of target RNAs activates DNA cleavage by the Type III-B CRISPR–Cas system
Authors: Elmore Joshua R. , Sheppard Nolan F. , Ramia Nancy , Deighan Trace , Li Hong , Terns Rebecca M. , Terns Michael P.
Published: February 2016

CRISPR–Cas systems eliminate nucleic acid invaders in bacteria and archaea. The effector complex of the Type III-B Cmr system cleaves invader RNAs recognized by the CRISPR RNA (crRNA ) of the complex. Here we show that invader RNAs also activate the Cmr complex to cleave DNA. As has been observed for other Type III systems, Cmr eliminates plasmid invaders in Pyrococcus furiosus by a mechanism that depends on transcription of the crRNA target sequence within the plasmid. Notably, we found that the target RNA per se induces DNA cleavage by the Cmr complex in vitro. DNA cleavage activity does not depend on cleavage of the target RNA but notably does require the presence of a short sequence adjacent to the target sequence within the activating target RNA (rPAM [RNA protospacer-adjacent motif]). The activated complex does not require a target sequence (or a PAM) in the DNA substrate. Plasmid elimination by the P. furiosus Cmr system also does not require the Csx1 (CRISPR-associated Rossman fold [CARF] superfamily) protein. Plasmid silencing depends on the HD nuclease and Palm domains of the Cmr2 (Cas10 superfamily) protein. The results establish the Cmr complex as a novel DNA nuclease activated by invader RNAs containing a crRNA target sequence and a rPAM.
Atg7 cooperates with Pten loss to drive prostate cancer tumor growth
Authors: Santanam Urmila , Banach-Petrosky Whitney , Abate-Shen Cory , Shen Michael M. , White Eileen , DiPaola Robert S.
Published: February 2016

Understanding new therapeutic paradigms for both castrate-sensitive and more aggressive castrate-resistant prostate cancer is essential to improve clinical outcomes. As a critically important cellular process, autophagy promotes stress tolerance by recycling intracellular components to sustain metabolism important for tumor survival. To assess the importance of autophagy in prostate cancer, we generated a new autochthonous genetically engineered mouse model (GEMM) with inducible prostate-specific deficiency in the Pten tumor suppressor and autophagy-related-7 (Atg7) genes. Atg7 deficiency produced an autophagy-deficient phenotype and delayed Pten-deficient prostate tumor progression in both castrate-naïve and castrate-resistant cancers. Atg7-deficient tumors display evidence of endoplasmic reticulum (ER) stress, suggesting that autophagy may promote prostate tumorigenesis through management of protein homeostasis. Taken together, these data support the importance of autophagy for both castrate-naïve and castrate-resistant growth in a newly developed GEMM, suggesting a new paradigm and model to study approaches to inhibit autophagy in combination with known and new therapies for advanced prostate cancer.
Somatic overgrowth associated with homozygous mutations in both MAN1B1 and SEC23A
Authors: Gupta Swati , Fahiminiya Somayyeh , Wang Tracy , Dempsey Nunez Laura , Rosenblatt David S. , Gibson William T. , Gilfix Brian , Bergeron John J. M. , Jerome-Majewska Loydie A.
Published: February 2016

Using whole-exome sequencing, we identified homozygous mutations in two unlinked genes, SEC23A c.1200G>C (p.M400I) and MAN1B1 c.1000C>T (p.R334C), associated with congenital birth defects in two patients from a consanguineous family. Patients presented with carbohydrate-deficient transferrin, tall stature, obesity, macrocephaly, and maloccluded teeth. The parents were healthy heterozygous carriers for both mutations and an unaffected sibling with tall stature carried the heterozygous mutation in SEC23A only. Mutations in SEC23A are responsible for craniolenticosultura dysplasia (CLSD). CLSD patients are short, have late-closing fontanels, and have reduced procollagen (pro-COL1A1) secretion because of abnormal pro-COL1A1 retention in the endoplasmic reticulum (ER). The mutation we identified in MAN1B1 was previously associated with reduced MAN1B1 protein and congenital disorders of glycosylation (CDG). CDG patients are also short, are obese, and have abnormal glycan remodeling. Molecular analysis of fibroblasts from the family revealed normal levels of SEC23A in all cells and reduced levels of MAN1B1 in cells with heterozygous or homozygous mutations in SEC23A and MAN1B1. Secretion of pro-COL1A1 was increased in fibroblasts from the siblings and patients, and pro-COL1A1 was retained in Golgi of heterozygous and homozygous mutant cells, although intracellular pro-COL1A1 was increased in patient fibroblasts only. We postulate that increased pro-COL1A1 secretion is responsible for tall stature in these patients and an unaffected sibling, and not previously discovered in patients with mutations in either SEC23A or MAN1B1. The patients in this study share biochemical and cellular characteristics consistent with mutations in MAN1B1 and SEC23A, indicating a digenic disease.
Analysis of multicrystal pump–probe data sets. II. Scaling of ratio data sets
Authors: Fournier Bertrand , Sokolow Jesse , Coppens Philip
Published: February 2016

Two methods for scaling of multicrystal data collected in time-resolved photocrystallography experiments are discussed. The WLS method is based on a weighted least-squares refinement of laser-ON/laser-OFF intensity ratios. The other, previously applied, is based on the average absolute system response to light exposure. A more advanced application of these methods for scaling within a data set, necessary because of frequent anisotropy of light absorption in crystalline samples, is proposed. The methods are applied to recently collected synchrotron data on the tetra-nuclear compound Ag2Cu2L4withL= 2-diphenylphosphino-3-methylindole. A statistical analysis of the weighted least-squares refinement residual terms is performed to test the importance of the scaling procedure.
Crystal structure offac-tricarbonyl(cyclohexyl isocyanide-κC)(quinoline-2-carboxylato-κ2N,O)rhenium(I)
Authors: Triantis Charalampos , Shegani Antonio , Kiritsis Christos , Raptopoulou Catherine , Psycharis Vassilis , Pelecanou Maria , Pirmettis Ioannis , Papadopoulos Minas
Published: February 2016

In the title compound, [Re(C10H6NO2)(C7H11N)(CO)3], the ReIatom is coordinated by three carbonyl ligands in a facial arrangement and by the N, O and C atoms from a chelating quinaldate anion and a monodentate isocyanide ligand, respectively. The resultant C4NO coordination sphere is distorted octahedral. A lengthening of the axial Re—CO bondtransto the isocyanide ligand is indicative of thetranseffect. Individual complexes are stacked into rods parallel to [001] through displaced π–π interactions. Weak C—H...O hydrogen-bonding interactions between the rods lead to the formation of layers parallel to (010). These layers are stacked along [010] by C—H...H—C van der Waals contacts.
Crystal structures of four chiral imine-substituted thiophene derivatives
Authors: Hernández-Téllez Guadalupe , Bernès Sylvain , Mendoza Angel , Ríos-Merino Francisco Javier , Moreno Gloria E. , Portillo Oscar , Gutiérrez René
Published: February 2016

A series of thiophenes substituted in positions 2 and 5 by imine groups have been synthesized using a solvent-free approach, and their crystal structures determined. The substituents are chiral groups, and the expected absolute configuration for each molecule was confirmed by refinement of the Flack parameter. The compounds are 2,5-bis[(S)-(+)-(1,2,3,4-tetrahydronaphthalen-1-yl)imino]thiophene, C26H26N2S, (I), 2,5-bis{[(R)-(−)-1-(4-methoxyphenyl)ethyl]iminomethyl}thiophene, C24H26N2O2S, (II), 2,5-bis{[(R)-(−)-1-(4-fluorophenyl)ethyl]iminomethyl}thiophene, C22H20F2N2S, (III), and 2,5-bis{[(S)-(+)-1-(4-chlorophenyl)ethyl]iminomethyl}thiophene, C22H20Cl2N2S, (IV). A common feature of all four molecules is the presence of twofold symmetry. For (I), which crystallizes in the triclinic space groupP1, this symmetry is non-crystallographic, but for (II) inC2 and the isomorphous structures (III) and (IV) that crystallize inP21212, the twofold symmetry is crystallographically imposed with one half of each molecule in the asymmetric unit. The comparable molecular symmetry in the four structures is also reflected in similar packing, with molecules aggregated to form chains through weak C—H...S interactions.
An explanatory model of attitudinal fear of HIV/AIDS testing in the construction industry
Authors: Bowen Paul , Govender Rajen , Edwards Peter , Cattell Keith
Published: February 2016

Purpose

– Prevalence of HIV/AIDS infection in the South African construction industry exceeds that of most other economic sectors. Voluntary counselling and testing is pivotal in combatting the spread of the disease. Little is known about the attitudinal fear of testing among construction workers, and the determinants thereof. The purpose of this paper is to address these shortcomings.

Design/methodology/approach

– A conceptual integrated model of fear of testing is proposed. Demographic characteristics and behavioural and cognitive factors are posited to explain attitudinal fear of testing. Regression analysis and structural equation modelling are used to test the model, using data gathered from 512 site-based participants in a questionnaire survey.

Findings

– Prejudice and lifestyle risk are the terminal predictors of fear of testing. Prejudice is determined by education level and HIV/AIDS transmission knowledge. Knowledge is predicted by education level and ethnicity. Lifestyle risk is determined by age, gender, harmful substance use, and knowledge. Harmful substance use is determined by age, gender, ethnicity, and employment type. The inter-relationship between knowledge about HIV/AIDS, prejudice towards HIV+ persons, and fear of testing is complex and nuanced.

Practical implications

– Intervention strategies by firms should positively address attitudinal fear of testing. Employers should ensure that effective communication is established with workers. Interventions relating to harmful substance use by employees need particular attention. Awareness campaigns should be sensitive to ethnic and cultural values, and to inter-generational differences.

Originality/value

– Harmful substance use and knowledge about HIV/AIDS transmission are indirect predictors of fear of testing. Education and ethnicity are critical dimensions of knowledge. The complex inter-relationship between knowledge, prejudice, lifestyle risk, and fear of testing is highlighted, providing guidelines for intervention management.
Agile, adaptive leaders
Authors: McPherson Blair
Published: February 2016

Purpose

– This paper aims to illustrate what agile management looks like, why it is increasingly necessary and how it can be developed and supported.

Design/methodology/approach

– This is a case study from a large complex organization (Lancashire County Council) showing how management restructuring increased managers
'
spans of responsibility, moving them out of their professional comfort zones, and how in response, the organization identified, supported and developed agile leadership.

Findings

– Agile, adaptive leaders are able to move quickly and easily from one area of management to another, able to manage a diverse range of complex services and able to quickly and smoothly adapt to a fast-changing business environment.

Research limitations/implications

– This is a case study from a large complex public sector organization, but the need for agile and adaptive leaders applies equally to the private and not-for-profit sectors.

Originality/value

– This paper offers insights into the changing role of management across a diverse range of services and provides an example of how organizations can successfully respond.
Improving communication among healthcare workers: a controlled study
Authors: Eklof Mats , Ahlborg Jr Gunnar
Published: February 2016

Purpose

– This paper aims to test the effects on aspects of workplace communication relevant to teamwork, and social support, in hospital units, of a dialog training (DT) intervention based on knowledge of key quality aspects related to interpersonal work-related communication among healthcare workers.

Design/methodology/approach

– A cluster randomized controlled study conducted among approximately 300 Swedish healthcare workers employed at ten hospital units. Workplace communication was measured in the form of participative safety, trust/openness, and social support. Effects were tested at three-month and six-month follow-ups. Repeated measurements were made.

Findings

– The results indicated that DT had a positive influence on participative safety and social support from managers. A positive tendency was observed for trust/openness.

Originality/value

– Developing and practicing good staff communication in hospital units is an important area for interventions designed to improve job performance and health.
Effects of post‐glacial phylogeny and genetic diversity on the growth variability and climate sensitivity of European silver fir
Authors: Bosela Michal , Popa Ionel , Gömöry Dušan , Longauer Roman , Tobin Brian , Kyncl Josef , Kyncl Tomas , Nechita Constantin , Petráš Rudolf , Sidor Cristian Gheorghe , Šebeň Vladimír , Büntgen Ulf
Published: February 2016

Growth rates of European silver fir (Abies alba Mill.) rapidly increased in the last century. At the same time, ring widths declined at the species southern distribution limits in the Mediterranean. Such diverse growth trends and responses have largely been attributed to regional climate conditions, but this was prior to considering the species' post‐glacial phylogeny.

A dendrochronological network composed of 1961 tree‐ring width series (TRW) from 78 silver fir sites between 365 and 1400 m a.s.l. along the Carpathian Arc was compiled. Spatial differences in the species' genetic diversity were investigated from genetic data of 69 silver fir populations in the region. Differences in growth variability and climate sensitivity were then related to post‐glacial phylogeny and genetic diversity.

Significant differences in interannual and longer‐term growth trends and climate responses across the Carpathian Arc were found to coincide with the geographical north–south separation of two post‐glacial populations from effective refugia originating from the Apennine and Balkan peninsulas. Summer temperature was the main driver of growth in the western (Apennine) lineage, whereas ring widths in the Balkan population from the east were predominantly controlled by summer drought. Fir specimens that originated from the Balkan lineage exhibited higher genetic diversity and more regular growth dynamics and also appeared to be less sensitive to air pollution during the 1970s.

Synthesis. Although the phylogeny of forest trees has largely been neglected in most dendroecological studies, results here indicate the importance of different post‐glacial histories for the growth sensitivity and adaptability to varying environmental factors. Decision‐making under future climate warming scenarios (for building resilience through forest management) should therefore consider different phylogenetic origins.
New Method for the Approximation of Corrected Calcium Concentrations in Chronic Kidney Disease Patients
Authors: Kaku Yoshio , Ookawara Susumu , Miyazawa Haruhisa , Ito Kiyonori , Ueda Yuichirou , Hirai Keiji , Hoshino Taro , Mori Honami , Yoshida Izumi , Morishita Yoshiyuki , Tabei Kaoru
Published: February 2016

The following conventional calcium correction formula (Payne) is broadly applied for serum calcium estimation: corrected total calcium (TCa) (mg/dL) = TCa (mg/dL) + (4 – albumin (g/dL)); however, it is inapplicable to chronic kidney disease (CKD) patients. A total of 2503 venous samples were collected from 942 all‐stage CKD patients, and levels of TCa (mg/dL), ionized calcium ([iCa2+] mmol/L), phosphate (mg/dL), albumin (g/dL), and pH, and other clinical parameters were measured. We assumed corrected TCa (the gold standard) to be equal to eight times the iCa2+ value (measured corrected TCa). Then, we performed stepwise multiple linear regression analysis by using the clinical parameters and derived a simple formula for corrected TCa approximation. The following formula was devised from multiple linear regression analysis: Approximated  corrected TCa (mg/dL) = TCa + 0.25 × (4 − albumin) + 4 × (7.4 − p H) + 0.1 × (6 − phosphate) + 0.3. Receiver operating characteristic curves analysis illustrated that area under the curve of approximated corrected TCa for detection of measured corrected TCa ≥ 8.4 mg/dL and ≤ 10.4 mg/dL were 0.994 and 0.919, respectively. The intraclass correlation coefficient demonstrated superior agreement using this new formula compared to other formulas (new formula: 0.826, Payne: 0.537, Jain: 0.312, Portale: 0.582, Ferrari: 0.362). In CKD patients, TCa correction should include not only albumin but also pH and phosphate. The approximated corrected TCa from this formula demonstrates superior agreement with the measured corrected TCa in comparison to other formulas.
A single multiplex PCR reaction for distinguishing strains of Queensland fruit fly Bactrocera tryoni (Diptera: Tephritidae)
Authors: Chen Yizhou , Dominiak Bernard C , O'Rourke Brendon A
Published: February 2016

The sterile insect technique (SIT) has been used to suppress or eradicate fruit flies. It is critical to be able to identify sterile and wild flies so that informed decisions can be made during eradication activities. The current dye marking approach can be flawed on a small number of occasions, and a genetic method is needed to test suspect misidentified samples. As a proof of concept, a single multiplex PCR with nine microsatellite markers was used to study the genetic structure of Queensland fruit flies Bactrocera tryoni (Froggatt) in 11 locations in southern New South Wales. Cluster analysis demonstrated that one cluster was exclusive to the sterile mass‐reared flies. A second distinct cluster was exclusive for one site in a wetter cooler area. The other sites were admixture of two main clusters. These nine microsatellite markers could be used to distinguish laboratory‐reared flies from field flies. The mass‐reared flies would need to be reanalysed after each introduction of wildness.
Love in the time of occupation: Reveries, longing, and intoxication in Kashmir
Authors: VARMA SAIBA
Published: February 2016

At a drug rehabilitation clinic in Indian‐occupied Kashmir, patients were subjected to a range of biomedical and penitentiary techniques. These techniques included group therapy sessions in which substance users performed narratives of their recovery—a practice that made visible their gratitude to the police, which oversaw the clinic and which, as an arm of the Indian military, many view as an illegal occupying force. While patients publicly pledged to remain sober and technically complied with the clinic's demands, they privately demonstrated ongoing commitments to nasha (intoxication), which places substance use, romantic love, and the search for divine unity in Sufism on the same phenomenological register. Through nasha, patients defied biomedical injunctions to forget their pasts and recuperated intoxication as a worthwhile experience. [addiction, substance abuse treatment, military humanitarianism, recovery, reverie, Kashmir]