bluuebunny/crossref_metadata_2025 huggingface dataset:
High resistance towards herbivore-induced habitat change in a high Arctic arthropod community
Authors: Schmidt Niels M. , Mosbacher Jesper B. , Eitzinger Bernhard , Vesterinen Eero J. , Roslin Tomas
Published: May 2018

Mammal herbivores may exert strong impacts on plant communities, and are often key drivers of vegetation composition and diversity. We tested whether such mammal-induced changes to a high Arctic plant community are reflected in the structure of other trophic levels. Specifically, we tested whether substantial vegetation changes following the experimental exclusion of muskoxen (
Ovibos moschatus
) altered the composition of the arthropod community and the predator–prey interactions therein. Overall, we found no impact of muskox exclusion on the arthropod community: the diversity and abundance of both arthropod predators (spiders) and of their prey were unaffected by muskox presence, and so was the qualitative and quantitative structure of predator–prey interactions. Hence, high Arctic arthropod communities seem highly resistant towards even large biotic changes in their habitat, which we attribute to the high connectance in the food web.
Overestimation of the adaptive substitution rate in fluctuating populations
Authors: Rousselle Marjolaine , Mollion Maeva , Nabholz Benoit , Bataillon Thomas , Galtier Nicolas
Published: May 2018

Estimating the proportion of adaptive substitutions (α) is of primary importance to uncover the determinants of adaptation in comparative genomic studies. Several methods have been proposed to estimateαfrom patterns polymorphism and divergence in coding sequences. However, estimators ofαcan be biased when the underlying assumptions are not met. Here we focus on a potential source of bias, i.e. variation through time in the long-term population size (N) of the considered species. We show via simulations that ancient demographic fluctuations can generate severe overestimations ofα, and this is irrespective of the recent population history.
Recommendations for Interpreting the Loss of Function PVS1 ACMG/AMP Variant Criteria
Authors: Abou Tayoun Ahmad N. , Pesaran Tina , DiStefano Marina T. , Oza Andrea , Rehm Heidi L. , Biesecker Leslie G. , Harrison Steven M. ,   on behalf of the ClinGen Sequence Variant Interpretation Working Group
Published: May 2018

The 2015 ACMG/AMP sequence variant interpretation guideline provided a framework for classifying variants based on several benign and pathogenic evidence criteria. This guideline includes a pathogenic criterion (PVS1) for predicted loss of function variants. However, the guideline did not elaborate on the specific considerations for the different types of loss of function variants, nor did it provide decision-making pathways assimilating information about the variant type, its location within the gene, or any additional evidence for the likelihood of a true null effect. Furthermore, the ACMG/AMP guideline did not take into account the relative strengths for each evidence type and the final outcome of their combinations with respect to PVS1 strength. Finally, criteria specifying the genes for which PVS1 can be used are still missing. Here, as part of the Clinical Genomic Resource (ClinGen) Sequence Variant Interpretation (SVI) Working Group’s goal of refining ACMG/AMP criteria, we provide recommendations for applying the PVS1 rule using detailed guidance addressing all the above-mentioned gaps. We evaluate the performance of the refined rule using heterogeneous types of loss of function variants (n = 56) curated by seven disease-specific groups across ten genes. Our recommendations will facilitate consistent and accurate interpretation of predicted loss of function variants.

GRANT NUMBERS

Research reported in this publication was supported by the National Human Genome Research Institute (NHGRI) under award number U41HG006834. LGB was supported by the Intramural Research Program of the NHGRI grant number HG200359 09.
Isavuconazole therapeutic drug monitoring associated to a pharmacogenetic exploration is far from being a pharmacologists’ whim
Authors: Darnaud L , Lamoureux F , Godet C , Pontier S , Debard A , Venisse N , Martins P , Concordet D , Gandia P
Published: May 2018

Isavuconazole is a new antifungal prodrug to treat invasive aspergillosis and mucormycosis, theoretically not requiring drug monitoring. However, we reported 4 clinical cases with toxic concentrations. Based on Desai’s population pharmacokinetic model, we estimated patients’ kinetic profile. Clearance was abnormally low, likely related to CYP3A4/5 polymorphisms. Thus, we recommend to collect blood sample just before the first maintenance dose to estimate pharmacokinetic profile and individualized dose. For patients presenting high concentrations, pharmacogenetics can be done.
The Clinical Imperative for Inclusivity: Race, Ethnicity, and Ancestry (REA) in Genomics
Authors: Popejoy A.B. , Ritter D.I. , Crooks K. , Currey E. , Fullerton S.M. , Hindorff L.A. , Koenig B. , Ramos E.M. , Sorokin E.P. , Wand H. , Wright M.W. , Zou J. , Gignoux C.R. , Bonham V.L. , Plon S.E. , Bustamante C.D. ,   The Clinical Genome Resource (ClinGen) Ancestry and Diversity Working Group (ADWG)
Published: May 2018

The Clinical Genome Resource (ClinGen) Ancestry and Diversity Working Group highlights the need to develop guidance on race, ethnicity, and ancestry (REA) data collection and use in clinical genomics. We present quantitative and qualitative evidence to characterize: 1) acquisition of REA data via clinical laboratory requisition forms, and 2) information disparity across populations in the Genome Aggregation Database (gnomAD) at clinically relevant sites as determined by variants in ClinVar. Our requisition form analysis showed substantial heterogeneity in clinical laboratory ascertainment of REA, as well as marked incongruity among terms used to define REA categories. There was also striking disparity across REA populations in the amount of information available about variants at clinically relevant sites in gnomAD. European ancestral populations constituted the majority of observations (55.8%), allele counts (59.7%), and private alleles (56.1%) in gnomAD at 550 loci with “pathogenic” and “likely pathogenic” expert-reviewed variants in ClinVar. Our findings highlight the importance of implementing and supporting programs to increase diversity in genome sequencing and clinical genomics, as well as measuring uncertainty around population-level datasets that are used in variant interpretation. Finally, we suggest the need for a standardized REA data collection framework to be developed and adopted across clinical genomics.
The Genetic Insulator RiboJ Increases Expression of Insulated Genes
Authors: Clifton Kalen P , Jones Ethan M , Paudel Sudip , Marken John P , Monette Callan E , Halleran Andrew D , Epp Lidia , Saha Margaret S
Published: May 2018

The self-cleaving ribozyme RiboJ is an insulator commonly used in genetic circuits to prevent unexpected interactions between neighboring parts. These interactions can compromise the modularity of the circuit, impeding the implementation of predictable genetic constructs. Despite its utility as an insulator, a quantitative assessment of the effect of RiboJ on the properties of downstream genetic parts is lacking. Here, we characterized the impact of insulation with RiboJ on expression of a reporter gene driven by a promoter from a library of 24 frequently employed constitutive promoters. We show that depending on the strength of the promoters, insulation with RiboJ increased protein abundance between twofold and tenfold and increased transcript abundance by an average of twofold. This result is the first to demonstrate that genetic insulators can impact the expression of downstream genes, potentially hindering the design of predictable genetic circuits and constructs.
TMEM106B, a risk factor for FTLD and aging, has an intrinsically disordered cytoplasmic domain
Authors: Kang Jian , Lim Liangzhong , Song Jianxing
Published: May 2018

TMEM106B was initially identified as a risk factor for FTLD, but recent studies highlighted its general role in neurodegenerative diseases. Very recently TMEM106B has also been characterized to regulate aging phenotypes. TMEM106B is a 274-residue lysosomal protein whose cytoplasmic domain functions in the endosomal/autophagy pathway by dynamically and transiently interacting with diverse categories of proteins but the underlying structural basis remains completely unknown. Here we conducted bioinformatics analysis and biophysical characterization by CD and NMR spectroscopy, and obtained results reveal that the TMEM106B cytoplasmic domain is intrinsically disordered with no well-defined three-dimensional structure. Nevertheless, detailed analysis of various multi-dimensional NMR spectra allowed defining residue-specific conformations and dynamics. Overall, the TMEM106B cytoplasmic domain is lacking of any tight tertiary packing and relatively flexible. However, several segments are populated with dynamic/nascent secondary structures and have relatively restricted backbone motions. In particular, the fragment Ser12-Met36 is highly populated with α- helix conformation. Our study thus decodes that being intrinsically disordered allows the TMEM106B cytoplasmic domain to dynamically and transiently interact with a variety of distinct partners.
dACC Response to Presentation of Negative Feedback Identifies Stimulant Dependence Diagnoses and Stimulant Use Severity
Authors: Claus Eric D. , Shane Matthew S.
Published: May 2018

Error-monitoring abnormalities in stimulant-dependent individuals (SDIs) may be due to reduced awareness of committed errors, or to reduced sensitivity upon such awareness. The distinction between these alternatives remains largely undifferentiated, but may have substantial clinical relevance. We sought to better characterize the nature, and clinical relevance, of SDIs’ error-monitoring processes by comparing carefully isolated neural responses during the presentation of negative feedback to a) stimulant dependence status and b) lifetime stimulant use. Forty-eight SDIs and twenty-three non-SDIs performed an fMRI-based time-estimation task specifically designed to isolate neural responses associated with the presentation (versus expectation) of contingent negative feedback. SDIs showed reduced dACC response compared to non-SDIs following the presentation of negative feedback, but only when error expectancies were controlled. Moreover, lifetime stimulant use correlated negatively with magnitude of dACC attenuation. While this findings was minimized after controlling for age, these results suggest that SDIs may be characterized by a core reduction in neural activity following error feedback, in the context of intact feedback expectancies. Correlations with lifetime stimulant use suggest that this neural attenuation may hold clinical significance.
Electrostatic repulsion causes anticooperative DNA binding between tumor suppressor ETS transcription factors and JUN-FOS at composite DNA sites
Authors: Madison Bethany J. , Clark Kathleen A. , Bhachech Niraja , Hollenhorst Peter C. , Graves Barbara J. , Currie Simon L.
Published: May 2018

Many transcription factors regulate gene expression in a combinatorial fashion often by binding in close proximity on composite cis-regulatory DNA elements. Here we investigate the molecular basis by which ETS transcription factors bind with AP1 transcription factors JUN-FOS at composite DNA-binding sites. The ability to bind to DNA with JUN-FOS correlates with the phenotype of these proteins in prostate cancer: the oncogenic ERG and ETV1/4/5 subfamilies co-occupy ETS-AP1 sites with JUN-FOS in vitro, whereas JUN-FOS robustly inhibits DNA binding by the tumor suppressors EHF and SPDEF. EHF binds to ETS-AP1 DNA with tighter affinity than ERG in the absence of JUN-FOS, which may enable EHF to compete with ERG and JUN-FOS for binding to ETS-AP1 sites. Genome-wide mapping of EHF and ERG binding sites in a prostate epithelial cell line reveal that EHF is preferentially excluded from closely spaced ETS-AP1 DNA sequences. Structural modeling and mutational analyses indicate that adjacent positively-charged surfaces from EHF and JUN-FOS disfavor simultaneous DNA binding due to electrostatic repulsion. The conservation of positively charged residues on the JUN-FOS interface identified ELF1 as an additional ETS factor that exhibits anticooperative DNA binding, and we present evidence that ELF1 is frequently downregulated in prostate cancer. In summary, the divergence of electrostatic features of ETS factors at their JUN-FOS interface enables distinct binding events at ETS-AP1 DNA sequences. We propose that this mechanism can drive unique targeting of ETS transcription factors, thereby facilitating distinct transcriptional programs.
Sensitive detection of LiveEscherichia coliby bacteriophage amplification-coupled immunoassay on the Luminex®MAGPIX instrument
Authors: Mido Tomotaka , Schaffer Eric M. , Dorsey Robert W. , Sozhamannan Shanmuga , Hofmann E. Randal
Published: May 2018

Phages are natural predators of bacteria and have been exploited in bacterial detection because of their exquisite specificity to their cognate bacterial hosts. In this study, we present a bacteriophage amplification-coupled assay as a surrogate for detecting a bacterium present in a sample. The assay entails detection of progeny phage resulting from infection and subsequent growth inside the bacterium present in suspected samples. This approach reduces testing time and enhances sensitivity to identify pathogens compared to traditional overnight plaque assay. Further, the assay has the ability to discriminate between live and dead cells since phages require live host cells to infect and replicate. To demonstrate its utility, phage MS2 amplification-coupled, bead-based sandwich type immunoassay on the Luminex®MAGPIX instrument forEscherichia colidetection was performed. The assay not only showed live cell discrimination ability but also a limit ofE. colidetection of 1×102cells/mL of live cells after a 3-hour incubation. In addition, the sensitivity of the assay was not impaired in the presence of dead cells. These results demonstrate that bacteriophage amplification-coupled assay can be a rapid live cell detection assay compared to traditional culture methods and a promising tool for quick validation of bacterial inactivation. Combined with the unique multiplex bead chemistry afforded by Luminex®MAGPIX platform, the phage assay can be expanded to be an ultra-deep multiplex assay for the simultaneous detection of multiple pathogens using specific phages directed against the target pathogens.
Enhancing the translational capacity ofE. coliby resolving the codon bias
Authors: Lipinszki Zoltan , Vernyik Viktor , Farago Nora , Sari Tobias , Puskas Laszlo G. , Blattner Frederick R. , Posfai Gyorgy , Gyorfy Zsuzsanna
Published: May 2018

Escherichia coliis a well-established, and popular host for heterologous expression of proteins. The preference in the choice of synonymous codons (codon bias), however, might differ for the host and the original source of the recombinant protein, constituting a potential bottleneck in production. Codon choice affects the efficiency of translation by a complex and poorly understood mechanism. The availability of certain tRNA species is one of the factors that may curtail the capacity of translation.

Here we provide a tRNA-overexpressing strategy that allows the resolution of the codon bias, and boosts the translational capacity of the popular host BL21(DE3) when rare codons are encountered. In BL21(DE3)-derived strain, called SixPack, copies of the genes corresponding to the six least abundant tRNA species have been assembled in a synthetic fragment and inserted into a ribosomal RNA operon. This arrangement, while not interfering with the growth properties of the new strain, allows dynamic control of the transcription of the extra tRNA genes, providing significantly elevated levels of the rare tRNAs in exponential growth phase.

Results from expression assays of a panel of heterologous proteins of diverse origin and codon composition showed that the performance of SixPack surpassed that of the parental BL21(DE3) or a related strain equipped with a rare tRNA-expressing plasmid.

Importance

Codon composition not fitting the codon bias of the expression host frequently compromises the efficient production of foreign proteins inE. coli. Various attempts to remedy the problem (codon optimization by gene synthesis, expression of rare tRNAs from a plasmid) proved to be unsatisfying. Our new approach, adjusting the tRNA pool by co-expressing extra copies of rare tRNA genes with ribosomal RNA genes, does not affect normal cell physiology, and seems to be a superior solution in terms of simplicity, cost, and yield.
Overexpression of the vascular brassinosteroid receptor BRL3 confers drought resistance without penalizing plant growth
Authors: Fàbregas Norma , Lozano-Elena Fidel , Blasco-Escámez David , Tohge Takayuki , Martínez-Andújar Cristina , Albacete Alfonso , Osorio Sonia , Bustamante Mariana , Riechmann José Luis , Nomura Takahito , Yokota Takao , Conesa Ana , Alfocea Francisco Pérez , Fernie Alisdair R. , Caño-Delgado Ana I.
Published: May 2018

Drought represents a major threat to food security. Mechanistic data describing plant responses to drought have been studied extensively and genes conferring drought resistance have been introduced into crop plants. However, plants with enhanced drought resistance usually display lower growth, highlighting the need for strategies to uncouple drought resistance from growth. Here, we show that overexpression of BRL3, a vascular-enriched member of the brassinosteroid receptor family, can confer drought stress tolerance in Arabidopsis. Whereas loss-of-function mutations in the ubiquitously expressed BRI1 receptor leads to drought resistance at the expense of growth, overexpression of BRL3 receptor confers drought tolerance without penalizing overall growth. Systematic analyses reveal that upon drought stress, increased BRL3 triggers the accumulation of osmoprotectant metabolites including proline and sugars. Transcriptomic analysis suggests that this results from differential expression of genes in the vascular tissues. Altogether, this data suggests that manipulating BRL3 expression could be used to engineer drought tolerant crops.
The Dance of the Interneurons: How Inhibition Facilitates Fast Compressible and Reversible Learning in Hippocampus
Authors: Nicola Wilten , Clopath Claudia
Published: May 2018

The hippocampus is capable of rapidly learning incoming information, even if that information is only observed once. Further, this information can be replayed in a compressed format in either forward or reversed modes during Sharp Wave Ripples (SPW-R). We leveraged state-of-the-art techniques in training recurrent spiking networks to demonstrate how primarily inhibitory networks of neurons in CA3 and CA1 can: 1) generate internal theta sequences or “time-cells” to bind externally elicited spikes in the presence of septal inhibition, 2) reversibly compress the learned representation in the form of a SPW-R when septal inhibition is removed, 3) generate and refine gamma-assemblies during SPW-R mediated compression, and 4) regulate the inter-ripple-interval timing between SPW-R’s in ripple clusters. From the fast time scale of neurons to the slow time scale of behaviors, inhibitory networks serve as the scaffolding for one-shot learning by replaying, reversing, refining, and regulating spike sequences.
Three enzymes and one substrate; regulation of flux through the glyoxylate shunt in the opportunistic pathogen,Pseudomonas aeruginosa
Authors: Crousilles Audrey , Dolan Stephen K. , Brear Paul , Chirgadze Dimitri Y. , Welch Martin
Published: May 2018

The glyoxylate shunt bypasses the oxidative decarboxylation steps of the tricarboxylic acid (TCA) cycle, thereby conserving carbon skeletons for biosynthesis. The branchpoint between the TCA cycle and the glyoxylate shunt is therefore widely considered to be one of the most important junctions in the whole of microbial metabolism. InEscherichia coli, AceK-mediated phosphorylation and inactivation of the TCA cycle enzyme,isocitrate dehydrogenase (ICD), is necessary to redirect flux through the first enzyme of the glyoxylate shunt,isocitrate lyase (ICL). In contrast, Mycobacterial species lack AceK and employ a phosphorylation-insensitiveisocitrate dehydrogenase (IDH) at the branchpoint. Flux partitioning here is controlled “rheostatically” through cross-activation of IDH by the product of ICL activity, glyoxylate. However, the opportunistic human pathogen,Pseudomonas aeruginosa, expresses IDH, ICD, ICL and AceK. Here, we present the structure, kinetics and regulation of each branchpoint enzyme. We show that flux partitioning is coordinated through reciprocal regulation of the enzymes involved, beautifully linking carbon flux with the availability of key gluconeogenic precursors in a way that cannot be extrapolated from an understanding of the branchpoint enzymes in other organisms.
Long-term expanding human airway organoids for disease modelling
Authors: Sachs Norman , Zomer-van Ommen Domenique D. , Papaspyropoulos Angelos , Heo Inha , Böttinger Lena , Klay Dymph , Weeber Fleur , Huelsz-Prince Guizela , Iakobachvili Nino , Viveen Marco C. , Lyubimova Anna , Teeven Luc , Derakhshan Sepideh , Korving Jeroen , Begthel Harry , Kumawat Kuldeep , Ramos Emilio , van Oosterhout Matthijs F.M. , Olimpio Eduardo P. , de Ligt Joep , Dijkstra Krijn K. , Smit Egbert F. , van der Linden Maarten , Voest Emile E. , van Moorsel Coline H.M. , van der Ent Cornelis K. , Cuppen Edwin , van Oudenaarden Alexander , Coenjaerts Frank E. , Meyaard Linde , Bont Louis J. , Peters Peter J. , Tans Sander J. , van Zon Jeroen S. , Boj Sylvia F. , Vries Robert G. , Beekman Jeffrey M. , Clevers Hans
Published: May 2018

Organoids are self-organizing 3D structures grown from stem cells that recapitulate essential aspects of organ structure and function. Here we describe a method to establish long-term-expanding human airway organoids from broncho-alveolar biopsies or lavage material. The pseudostratified airway organoid epithelium consists of basal cells, functional multi-ciliated cells, mucus-producing goblet cells, and CC10-secreting club cells. Airway organoids derived from cystic fibrosis (CF) patients allow assessment of CFTR function in an organoid swelling assay. Organoid culture conditions also allow gene editing as well as the derivation of various types of lung cancer organoids. Respiratory syncytial virus (RSV) infection recapitulated central disease features and dramatically increases organoid cell motility, found to be driven by the non-structural viral NS2 protein. We conclude that human airway organoids represent versatile models for the in vitro study of hereditary, malignant, and infectious pulmonary disease.
Local Contractions Regulate E-Cadherin Adhesions, Rigidity Sensing and Epithelial Cell Sorting
Authors: Yang Yian , Nguyen Emmanuelle , Narayana Gautham Hari Narayana Sankara , Heuzé Melina , Mège René-Marc , Ladoux Benoit , Sheetz Michael P.
Published: May 2018

E-cadherin is a major cell-cell adhesion molecule involved in mechanotransduction at cell-cell contacts in tissues. Since epithelial cells respond to rigidity and tension in the tissue through E-cadherin, there must be active processes that test and respond to the mechanical properties of these adhesive contacts. Using sub-micrometer, E-cadherin-coated PDMS pillars, we find that cells generate local contractions between E-cadherin adhesions and pull to a constant distance for a constant duration, irrespective of pillar rigidity. These cadherin contractions require non-muscle myosin IIB, tropomyosin 2.1, α-catenin and binding of vinculin to α-catenin; plus, they are correlated with rigidity-dependent cell spreading. Without contractions, cells fail to spread to different areas on soft and rigid surfaces and to maintain monolayer integrity. We further observe that cadherin contractions enable cells to test myosin IIA-mediated tension of neighboring cells, and sort out myosin IIA-depleted cells. Thus, we suggest that epithelial cells test and respond to the mechanical characteristics of neighboring cells through cadherin contractions.
Integrin and ligand-independent PDGFr signaling synergistically contribute to directional migration ofXenopusmesendoderm
Authors: Richardson Crystal M. , Dzamba Bette J. , Sonavane Pooja R. , DeSimone Douglas W.
Published: May 2018

Both PDGF signaling and adhesion to fibronectin (FN) matrix have been implicated in the directional collective migration ofXenopusmesendoderm cells at gastrulation. However, mesendoderm explants cultured on FN-coated substrates migrate directionally even in the absence of a source of PDGF. Integrin adhesion has been reported to up-regulate PDGF ligand-independent signaling through the PDGF receptor (PDGFr) in cultured mammalian cells. In order to address whether a similar mechanism stimulates PDGFr signaling in the absence of PDGF-A ligand in amphibian mesendoderm, isolated cells were cultured on bacterial fusion proteins containing the Type-III repeats 9-11 of FN (GST-9.11). Type III9-11contains the RGD and “synergy” (PPSRN) sites required for integrin α5β1 adhesion and activation but lacks the PDGF-A ligand-binding site present in the full-length FN protein. In order to ensure mesendoderm was not exposed to PDGFin vivoprior to removal and culturein vitro, antisense morpholinos were used to inhibit normal expression of PDGF-A ligand in embryos. P-Akt levels were reduced two-fold when either the PDGFr-α was knocked down or when cells were plated on GST-9.11a, which contains a point mutation (PPSRN>PPSAN) that prevents both full activation of integrin α5β1 and cell spreading. Reduced expression of PDGFr-α was accompanied by perturbations in tissue migration, cytoskeletal organization, polarity of cell protrusions, and focal adhesion area. Mesendoderm cells became rounded, and the actin and cytokeratin filaments appeared collapsed and often colocalized near the cell center. Taken together, these findings suggest that integrin adhesion to FN, acting in synergy with PDGFr-α, is sufficient to elevate PI3K-Akt signaling in the mesendoderm even in the absence of the PDGF-A ligand, and to promote forward-directed protrusions and directional tissue migration.
High stereographic resolution texture and residual stress evaluation using time-of-flight neutron diffraction
Authors: Xu Pingguang , Harjo Stefanus , Ojima Mayumi , Suzuki Hiroshi , Ito Takayoshi , Gong Wu , Vogel Sven C. , Inoue Junya , Tomota Yo , Aizawa Kazuya , Akita Koichi
Published: May 2018

Neutron diffraction texture measurements provide bulk averaged textures with excellent grain orientation statistics, even for large-grained materials, owing to the probed volume being of the order of 1 cm3. Furthermore, crystallographic parameters and other valuable microstructure information such as phase fraction, coherent crystallite size, root-mean-square microstrain, macroscopic or intergranular strain and stress, etc. can be derived from neutron diffractograms. A procedure for combined high stereographic resolution texture and residual stress evaluation was established on the pulsed-neutron-source-based engineering materials diffractometer TAKUMI at the Materials and Life Science Experimental Facility of the Japan Proton Accelerator Research Center, through division of the neutron detector panel regions. Pole figure evaluation of a limestone standard sample with a well known texture suggested that the precision obtained for texture measurement is comparable to that of the established neutron beamlines utilized for texture measurement, such as the HIPPO diffractometer at the Los Alamos Neutron Science Center (New Mexico, USA) and the D20 angle-dispersive neutron diffractometer at the Institut Laue–Langevin (Grenoble, France). A high-strength martensite–austenite multilayered steel was employed for further verification of the reliability of simultaneous Rietveld analysis of multiphase textures and macro stress tensors. By using a texture-weighted geometric mean micromechanical (BulkPathGEO) model, a macro stress tensor analysis with a plane stress assumption showed a rolling direction–transverse direction (RD–TD) in-plane compressive stress (about −330 MPa) in the martensite layers and an RD–TD in-plane tensile stress (about 320 MPa) in the austenite layers. The phase stress partitioning was ascribed mainly to the additive effect of the volume expansion during martensite transformation and the linear contraction misfit between austenite layers and newly transformed martensite layers during the water quenching process.
A multireflection and multiwavelength residual stress determination method using energy dispersive diffraction
Authors: Marciszko Marianna , Baczmański Andrzej , Klaus Manuela , Genzel Christoph , Oponowicz Adrian , Wroński Sebastian , Wróbel Mirosław , Braham Chedly , Sidhom Habib , Wawszczak Roman
Published: May 2018

The main focus of the presented work was the investigation of structure and residual stress gradients in the near-surface region of materials studied by X-ray diffraction. The multireflection method was used to measure depth-dependent stress variation in near-surface layers of a Ti sample (grade 2) subjected to different mechanical treatments. First, the multireflection grazing incidence diffraction method was applied on a classical diffractometer with Cu Kα radiation. The applicability of the method was then extended by using a white synchrotron beam during an energy dispersive (ED) diffraction experiment. An advantage of this method was the possibility of using not only more than one reflection but also different wavelengths of radiation. This approach was successfully applied to analysis of data obtained in the ED experiment. There was good agreement between the measurements performed using synchrotron radiation and those with Cu Kα radiation on the classical diffractometer. A great advantage of high-energy synchrotron radiation was the possibility to measure stresses as well as the a
0 parameter and c
0/a
0 ratio for much larger depths in comparison with laboratory X-rays.
Gold Cup: human resources as sources of competitive advantage and superior performance
Authors: Omondi-Ochieng Peter
Published: May 2018

Purpose

The purpose of this paper is twofold: first, to evaluate the association between human resources and qualification for the 2017 Gold Cup, and second, to examine if human resources could predict qualification for the 2017 Gold Cup.

Design/methodology/approach

Guided by four competitive advantage (CA) theories related to the human resources, the study utilized archival data of 35 male Gold Cup national football teams. The dependent variable was qualifications for 2017 Gold Cup and the independent variables were football-specific human capital measured by ranked number of football amateurs, professionals and officials. Statistical analysis was performed using Kendellτstatistic and binary logistic regression (BLR).

Findings

Qualification for the Gold Cup tournament and all human resources were positively and statistically associated (officials (0.493,p<0.01), amateurs (0.464,p<0.01) and professionals (0.624,p<0.01)), and BLR model (NegelkerkeR2) explained 55.8 percent of the variance of human resources.

Research limitations/implications

The research focused exclusively on football-specific human capital and not alternative sources of CA such as economy power, political stability and/or national football popularity amongst others.

Practical implications

Human resources are a valuable source of CA which requires long-term strategy geared toward training, development and promotion of talent. Superior football team performance is directly proportional to talented players.

Originality/value

The study was unique in two ways. First, it made clear the positive significance of human resources as a source of CA. Second, it highlighted the distinction between professional and amateur footballers – a factor uncommon in similar studies.
Bayesian-based conflict conversion path discovery for waste management policy implementation in China
Authors: Yang Qing , He Ling , Liu Xingxing , Cheng Mengying
Published: May 2018

Purpose

This study aims to analyze reform path for waste management policy implementation. With reference to the Bayesian theory, this study provides a dynamic policy conversion method through various context settings. Furthermore, this study attempts to present an empirical research paradigm.

Design/methodology/approach

Matland’s “ambiguity-conflict model” is applied to explain the problems and reform paths of China’s waste management policy implementation. Integrating structure discovery and bibliometrics into qualitative analysis, this study used search data from literature search engine with specific themes to achieve structure learning of Bayesian network with key factors refined in waste management policy.

Findings

The results show that China’s waste management policy implementation belongs to symbolic implementation with high ambiguity and high conflict. Four basic conversion paths for the waste management policy are proposed, which are classified by length and stability. Then, it is possible to locate the factors, paths and types of policy implementation through involvement analysis with features of each path and each district of policy implementation. Public education holds direct but unstable impact on waste management. Economic incentives hold continuous but gradually diminishing impact. Perceived policy effectiveness plays the crucial role like a central bridge. Resident conditions have a positive impact, which could be enhanced through economic development of China. The impact of subjective norm on waste management is not significant. But subjective norm has the potential breakthrough for solving stagnation of waste classification policy. However, the impacts from each factor may change along with economy growth and technology innovation.

Originality/value

This study uses the “ambiguity-conflict model” to position China’s waste classification policy and suggests that structure discovery methods help understand feasible reform paths for reform policy. The integration of theoretical analysis and quantitative simulation can achieve a comprehensive analysis of problems and solutions in waste management policy implementation of China. Promotion and education, economic incentives, perceived value, behavior control, subjective norm, perceived policy effectiveness, informal waste recycling system and residential conditions are explored as key factors for waste classification policy implementation as a representative in waste management policy. The role of each key factor and features of each conversion paths are integrated to position reform paths in the ambiguity-conflict model. This work helps to explain the stagnation of waste management policy implementation from the perspective of dynamic structure evolution, and some specific suggestions to get out of stagnation are proposed.
The path to mall patronage intentions is paved with 4E-based experiential value for Indian consumers
Authors: Sadachar Amrut , Fiore Ann Marie
Published: May 2018

Purpose

The purpose of this paper is to examine whether experiential offerings from two types of retailers play a significant role in consumer responses toward Indian malls. Specifically, this study examined the relationships between consumer perceptions of experience economy 4E constructs (i.e. educational, entertainment, escapist, and esthetic experiences) and experiential value associated with merchandise retailers and service retailers in Indian shopping malls, and between perceived experiential value and mall patronage intention.

Design/methodology/approach

A mall intercept survey conducted in two shopping malls in India resulted in 552 useable responses. Structural equation modeling was used to test the hypothesized relationships.

Findings

Experience economy constructs (i.e. entertainment, escapist, and esthetic experiences) contributed to the experiential value associated with merchandise retailers and/or service retailers in the mall. Experiential value associated with both merchandise retailers and service retailers in the mall positively influenced mall patronage intention.

Practical implications

The results have practical implications for mall retailers, mall managers, and mall developers; particular experiential strategies for both merchandise retailers and service retailers may improve patronage intentions toward the mall, which includes a measure of purchase intentions.

Originality/value

Although academic articles support the idea that retailers can obtain benefits by offering experiences to consumers, this is the first study to empirically validate the role of specific consumer experiences, the 4Es, resulting from both merchandise retailers and service retailers, in a non-Western mall context on value creation for shoppers and the consequent influence on patronage intentions.
The German source market perceptions: how risky is Turkey to travel to?
Authors: Isaac Rami K. , Velden Vanessa
Published: May 2018

Purpose

The purpose of this paper is to get a better understanding of the influence of terrorism on risk perception and attitudes of the German travel behavior toward Turkey as a destination in crisis, which has been considered one of the biggest losers for 2016.

Design/methodology/approach

The research process involved an online self-administered method created with one of the leading research and web-based survey tools called Qualtrics. This tool has been considered useful to reach a wider target, the questionnaire filled in by 305 respondents.

Findings

The findings revealed a strong tendency of a low safety perception among the sample toward Turkey. Furthermore, a large proportion indicated a strong unlikelihood of traveling to the country within the upcoming 12 months independently of a past travel experience. In addition, Turkey and Egypt were the countries perceived as most unsafe among the mentioned destinations.

Research limitations/implications

The majority of the respondents of the study were aged between 50 and 59 years and were employed as commercial employee, office or administration workers. The outcomes might be different for a higher sample size with a tendency of various demographic characteristic such as age and profession. Furthermore, the study should be repeated while focusing on respondents with accompanied children on holidays, which only made up a minority for the present research study.

Originality/value

To the best of the knowledge, this is the first study to examine the influence of terrorism on risk perception and attitudes of the German travel behavior toward Turkey and their risk reduction strategies/preventive measures.
A study of crowd-collaborative learning: an empirical study
Authors: Lin Wen-Shan , Wang Yi-Ju , Chen Hong-Ren
Published: May 2018

Purpose

Information technology is widely applied for completing group tasks and enhancing learning in computer-supported collaborative learning (CSCL) environment. Group members not only complete tasks but also learn ideas from other members of the group. These ideas can be better than what individual could come up with. As these ideas are referred as an upward comparison in the perspective of social comparison theory. However, there are limited studies that provide evidence in investigating how social comparison orientation (SCO) perceived by individual learner impacts on learning and group performance. The paper aims to discuss these issues.

Design/methodology/approach

This study experimentally tackles this problem at both individual and group level. An experimental study was applied in this study. Structural equation modeling and hierarchical linear modeling approaches are used to validate the data.

Findings

Results of 168 subjects reveal that SCO does have associations with group performance and learning performance respectively. Discussions and implications for literature and practice are given at the end of the paper.

Originality/value

This study confirms that the social genesis occurs more effectively through social interactions in CSCL. It also extends our understandings about the impacts of SCO. Results reveal that the higher level of SCO adopted by group members, the higher level of social interactions at group level can be triggered. As a result, the group performance can be enhanced. On one hand, these findings bridge the research gap in terms of investigating the notion of SCT on CSCL. On the other hand, it provides a possible solution in alleviating the problem of social loafing as commonly observed in CSCL. Therefore, these findings fulfilled the two research objectives.
Value innovation and how to successfully incubate “blue ocean” initiatives
Authors: Leavy Brian
Published: May 2018

Purpose

This masterclass examines the blue ocean value innovation process, how it works in practice and how it has evolved since the publication of Blue Ocean Strategy (2005) by W. Chan Kim and Renee Mauborgne as explored in their new book their new book Blue Ocean Shift (2017).

Design/methodology/approach

The main focus is the value innovation methodology that underlies blue ocean strategy.

Findings

Blue ocean strategy is a process of value innovation that uncovers new aggregations of demand by redefining the offering category.

Practical implications

Blue ocean strategy tends to focus on value innovation that uncovers new aggregations of demand by redefining the category while disruptive innovation tends to concentrate on new demand-creation that expands the current served market.

Originality/value

Blue ocean strategy sets out to reconfigure value propositions in compelling new ways that can deliver a quantum leap beyond the current red ocean value-cost frontier through raising buyer value and lowering company costs simultaneously. The emphasis on both value and innovation is essential to the creation of new “blue ocean” market spaces.
Customized reconstruction with modified keystone flaps
Authors: Lee Jang Won , Kim Chan Woo , Park Tae Hwan
Published: May 2018

The reconstruction of soft tissue defects with a similar type of tissue and minimizing morbidities are important. Herein, we describe our surgical experience using customized reconstruction with a series of modified keystone flaps. We retrospectively reviewed data of 48 consecutive soft tissue reconstructions using modified keystone flaps between March and December 2017. Soft tissue reconstruction was performed and there was no major complication in the follow‐up period. The dimensions of the wound defect ranged from 1 × 1 cm2 to 20 × 18 cm2 with a mean size of 4.7 × 3.5 cm2, while the dimensions of the customized keystone design flap ranged from 2 × 1 cm2 to 23 × 19 cm2 with a mean size of 7.9 × 5.4 cm2. Minor dehiscence in three cases (6%) and partial flap loss in one case (2%) were noticed. Two cases healed spontaneously and other two cases were surgically recovered. Due to its simplicity, reliability, versatility and minimal morbidity, our modified keystone flaps could be excellent surgical options in various soft tissue reconstructions.
Modelling the wave phenomena in acoustic and elastic media with sharp variations of physical properties using the grid‐characteristic method
Authors: Favorskaya Alena V. , Zhdanov Michael S. , Khokhlov Nikolay I. , Petrov Igor B.
Published: May 2018

This paper introduces a novel method of modelling acoustic and elastic wave propagation in inhomogeneous media with sharp variations of physical properties based on the recently developed grid‐characteristic method which considers different types of waves generated in inhomogeneous linear‐elastic media (e.g., longitudinal, transverse, Stoneley, Rayleigh, scattered PP‐, SS‐waves, and converted PS‐ and SP‐waves). In the framework of this method, the problem of solving acoustic or elastic wave equations is reduced to the interpolation of the solutions, determined at earlier time, thus avoiding a direct solution of the large systems of linear equations required by the FD or FE methods. We apply the grid‐characteristic method to compare wave phenomena computed using the acoustic and elastic wave equations in geological medium containing a hydrocarbon reservoir or a fracture zone. The results of this study demonstrate that the developed algorithm can be used as an effective technique for modelling wave phenomena in the models containing hydrocarbon reservoir and/or the fracture zones, which are important targets of seismic exploration.
Metformin directly targets the H3K27me3 demethylase KDM6A/UTX
Authors: Cuyàs Elisabet , Verdura Sara , Llorach‐Pares Laura , Fernández‐Arroyo Salvador , Luciano‐Mateo Fedra , Cabré Noemí , Stursa Jan , Werner Lukas , Martin‐Castillo Begoña , Viollet Benoit , Neuzil Jiri , Joven Jorge , Nonell‐Canals Alfons , Sanchez‐Martinez Melchor , Menendez Javier A.
Published: May 2018

Metformin, the first drug chosen to be tested in a clinical trial aimed to target the biology of aging per se, has been clinically exploited for decades in the absence of a complete understanding of its therapeutic targets or chemical determinants. We here outline a systematic chemoinformatics approach to computationally predict biomolecular targets of metformin. Using several structure‐ and ligand‐based software tools and reference databases containing 1,300,000 chemical compounds and more than 9,000 binding sites protein cavities, we identified 41 putative metformin targets including several epigenetic modifiers such as the member of the H3K27me3‐specific demethylase subfamily, KDM6A/UTX. AlphaScreen and AlphaLISA assays confirmed the ability of metformin to inhibit the demethylation activity of purified KDM6A/UTX enzyme. Structural studies revealed that metformin might occupy the same set of residues involved in H3K27me3 binding and demethylation within the catalytic pocket of KDM6A/UTX. Millimolar metformin augmented global levels of H3K27me3 in cultured cells, including reversion of global loss of H3K27me3 occurring in premature aging syndromes, irrespective of mitochondrial complex I or AMPK. Pharmacological doses of metformin in drinking water or intraperitoneal injection significantly elevated the global levels of H3K27me3 in the hepatic tissue of low‐density lipoprotein receptor‐deficient mice and in the tumor tissues of highly aggressive breast cancer xenograft‐bearing mice. Moreover, nondiabetic breast cancer patients receiving oral metformin in addition to standard therapy presented an elevated level of circulating H3K27me3. Our biocomputational approach coupled to experimental validation reveals that metformin might directly regulate the biological machinery of aging by targeting core chromatin modifiers of the epigenome.
Brief Report: The effect of implementing a tobacco treatment service on adherence to evidence‐based practice in an inpatient state‐owned psychiatric hospital
Authors: Okoli Chizimuzo T. C. , Al‐Mrayat Yazan D. , Stead Barbara
Published: May 2018

Background and Objectives

The Centers for Medicare and Medicaid Services (CMS) requires reporting of specific tobacco treatment (TT) measures. We examined compliance to these measures before and after initiation of a specialized TT service in a state‐psychiatric hospital.

Methods

Using a retrospective analysis, patient records (N = 3669) were examined, using one‐way ANOVAs, for changes in rates of tobacco use screening and treatment between September–December 2015 (pre‐implementation of CMS requirements), and January–April, May–August, and September–December 2016 (post‐implementation of the CMS requirements).

Results

We found significant increases, between Sep–Dec 2015 and Sep–Dec 2016, in the rates of tobacco use screening (93.4–95.3%, F [3, 12] = 7.39, p = .005), offering TT counseling (68.1–76.5%, F [1] = 18.59, p = .001) and medications (71.7–76.5%, F [1] = 5.86, p = .032).

Conclusions and Significance

Our findings can provide guidance to enhance compliance with TT measures in psychiatric settings. (Am J Addict 2018;27:368–371)