bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational discovery of pathway-level genetic vulnerabilities in non-small-cell lung cancer
Authors: Young Jonathan H. , Peyton Michael , Seok Kim Hyun , McMillan Elizabeth , Minna John D. , White Michael A. , Marcotte Edward M.
Published: February 2016

Motivation: Novel approaches are needed for discovery of targeted therapies for non-small-cell lung cancer (NSCLC) that are specific to certain patients. Whole genome RNAi screening of lung cancer cell lines provides an ideal source for determining candidate drug targets.

Results: Unsupervised learning algorithms uncovered patterns of differential vulnerability across lung cancer cell lines to loss of functionally related genes. Such genetic vulnerabilities represent candidate targets for therapy and are found to be involved in splicing, translation and protein folding. In particular, many NSCLC cell lines were especially sensitive to the loss of components of the LSm2-8 protein complex or the CCT/TRiC chaperonin. Different vulnerabilities were also found for different cell line subgroups. Furthermore, the predicted vulnerability of a single adenocarcinoma cell line to loss of the Wnt pathway was experimentally validated with screening of small-molecule Wnt inhibitors against an extensive cell line panel.

Availability and implementation: The clustering algorithm is implemented in Python and is freely available at https://bitbucket.org/youngjh/nsclc_paper.

Contact:  marcotte@icmb.utexas.edu or jon.young@utexas.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
MTG2: an efficient algorithm for multivariate linear mixed model analysis based on genomic information
Authors: Lee S. H. , van der Werf J. H. J.
Published: February 2016

Summary: We have developed an algorithm for genetic analysis of complex traits using genome-wide SNPs in a linear mixed model framework. Compared to current standard REML software based on the mixed model equation, our method is substantially faster. The advantage is largest when there is only a single genetic covariance structure. The method is particularly useful for multivariate analysis, including multi-trait models and random regression models for studying reaction norms. We applied our proposed method to publicly available mice and human data and discuss the advantages and limitations.

Availability and implementation: MTG2 is available in https://sites.google.com/site/honglee0707/mtg2.

Contact:  hong.lee@une.edu.au

Supplementary information:  Supplementary data are available at Bioinformatics online.
EPI-peptide designer: a tool for designing peptide ligand libraries based on epitope–paratope interactions
Authors: Viart B. , Dias-Lopes C. , Kozlova E. , Oliveira C. F. B. , Nguyen C. , Neshich G. , Chávez-Olórtegui C. , Molina F. , Felicori L. F.
Published: February 2016

Motivation: Antibodies are an important class of biological drugs, but with limitations, such as inadequate pharmacokinetics, adverse immunogenicity and high production costs. Synthetic peptides for the desired target represent an important alternative to antibodies. However, no computational tool exists to guide the design of these peptides.

Results: To identify the interacting residues in a given antibody–antigen (Ab–Ag) interface we used Interface Interacting Residue (I2R), a selection method based on computed molecular interactions. The aggregation of all the molecular interactions between epitope and paratope residues allowed us to transform the 3D Ab–Ag complex structures into interface graphs. Based on these data and the probability of molecular interaction we developed EPI-Peptide Designer tool that uses predicted paratope residues for an epitope of interest to generate targeted peptide ligand libraries. EPI-Peptide Designer successfully predicted 301 peptides able to bind to LiD1 target protein (65% of the experimentally tested peptides), an enrichment of 22% compared to randomly generated peptides. This tool should enable the development of a new generation of synthetic interacting peptides that could be very useful in the biosensor, diagnostic and therapeutic fields.

Availability and implementation: All software developed in this work are available at http://www.biocomp.icb.ufmg.br/biocomp/

Contact:  liza@icb.ufmg.br

Supplementary information:  Supplementary data are available at Bioinformatics online.
GeneValidator: identify problems with protein-coding gene predictions
Authors: Drăgan Monica-Andreea , Moghul Ismail , Priyam Anurag , Bustos Claudio , Wurm Yannick
Published: February 2016

Summary: Genomes of emerging model organisms are now being sequenced at very low cost. However, obtaining accurate gene predictions remains challenging: even the best gene prediction algorithms make substantial errors and can jeopardize subsequent analyses. Therefore, many predicted genes must be time-consumingly visually inspected and manually curated. We developed GeneValidator (GV) to automatically identify problematic gene predictions and to aid manual curation. For each gene, GV performs multiple analyses based on comparisons to gene sequences from large databases. The resulting report identifies problematic gene predictions and includes extensive statistics and graphs for each prediction to guide manual curation efforts. GV thus accelerates and enhances the work of biocurators and researchers who need accurate gene predictions from newly sequenced genomes.

Availability and implementation: GV can be used through a web interface or in the command-line. GV is open-source (AGPL), available at https://wurmlab.github.io/tools/genevalidator.

Contact: y.wurm@qmul.ac.uk

Supplementary information:  Supplementary data are available at Bioinformatics online.
Inclusion of dyad-repeat pattern improves topology prediction of transmembrane β-barrel proteins
Authors: Hayat Sikander , Peters Christoph , Shu Nanjiang , Tsirigos Konstantinos D. , Elofsson Arne
Published: February 2016

Summary: Accurate topology prediction of transmembrane β-barrels is still an open question. Here, we present BOCTOPUS2, an improved topology prediction method for transmembrane β-barrels that can also identify the barrel domain, predict the topology and identify the orientation of residues in transmembrane β-strands. The major novelty of BOCTOPUS2 is the use of the dyad-repeat pattern of lipid and pore facing residues observed in transmembrane β-barrels. In a cross-validation test on a benchmark set of 42 proteins, BOCTOPUS2 predicts the correct topology in 69% of the proteins, an improvement of more than 10% over the best earlier method (BOCTOPUS) and in addition, it produces significantly fewer erroneous predictions on non-transmembrane β-barrel proteins.

Availability and implementation: BOCTOPUS2 webserver along with full dataset and source code is available at http://boctopus.bioinfo.se/

Contact: arne@bioinfo.se

Supplementary information:  Supplementary data are available at Bioinformatics online.
Quantitative trait association study for mean telomere length in the South Asian genomes
Authors: Hakobyan Anna , Nersisyan Lilit , Arakelyan Arsen
Published: February 2016

Motivation: Mean telomere length (MTL) is associated with cancers and age-related diseases, which necessitates identification of genomic and environmental factors that impact telomere length dynamics. Here, we present a pilot genome wide association (GWA) study for MTL in South Asian population using publicly available next generation whole genome sequences (WGS), both for MTL and genotype calculations.

Results: MTL in the studied population was not correlated with age, which is in accordance with previous reports. Further, we identified that individuals with Sikh religion had longer telomeres, which may be the result of complex interaction between genetic background and environmental factors. Finally, we identified 51 MTL-associated SNPs residing in five loci. The top ones were located in ADARB2 gene, which has previously been implicated with extreme old age.

Conclusion: Our results show that WGS data can be used in telomere length studies. In addition, we introduce novel loci implicated in MTL that may be worth considering in further telomere studies.

Contact:  aarakelyan@sci.am

Supplementary information:  Supplementary data are available at Bioinformatics online.
GiANT: gene set uncertainty in enrichment analysis
Authors: Schmid Florian , Schmid Matthias , Müssel Christoph , Sträng J. Eric , Buske Christian , Bullinger Lars , Kraus Johann M. , Kestler Hans A.
Published: February 2016

Summary: Over the past years growing knowledge about biological processes and pathways revealed complex interaction networks involving many genes. In order to understand these networks, analysis of differential expression has continuously moved from single genes towards the study of gene sets. Various approaches for the assessment of gene sets have been developed in the context of gene set analysis (GSA). These approaches are bridging the gap between raw measurements and semantically meaningful terms.

We present a novel approach for assessing uncertainty in the definition of gene sets. This is an essential step when new gene sets are constructed from domain knowledge or given gene sets are suspected to be affected by uncertainty. Quantification of uncertainty is implemented in the R-package GiANT. We also included widely used GSA methods, embedded in a generic framework that can readily be extended by custom methods. The package provides an easy to use front end and allows for fast parallelization.

Availability and implementation: The package GiANT is available on CRAN.

Contacts:  hans.kestler@leibniz-fli.de or hans.kestler@uni-ulm.de
ELASPIC web-server: proteome-wide structure-based prediction of mutation effects on protein stability and binding affinity
Authors: Witvliet Daniel K. , Strokach Alexey , Giraldo-Forero Andrés Felipe , Teyra Joan , Colak Recep , Kim Philip M.
Published: February 2016

Summary: ELASPIC is a novel ensemble machine-learning approach that predicts the effects of mutations on protein folding and protein–protein interactions. Here, we present the ELASPIC webserver, which makes the ELASPIC pipeline available through a fast and intuitive interface. The webserver can be used to evaluate the effect of mutations on any protein in the Uniprot database, and allows all predicted results, including modeled wild-type and mutated structures, to be managed and viewed online and downloaded if needed. It is backed by a database which contains improved structural domain definitions, and a list of curated domain–domain interactions for all known proteins, as well as homology models of domains and domain–domain interactions for the human proteome. Homology models for proteins of other organisms are calculated on the fly, and mutations are evaluated within minutes once the homology model is available.

Availability and implementation: The ELASPIC webserver is available online at http://elaspic.kimlab.org.

Contact:  pm.kim@utoronto.ca or pi@kimlab.org

Supplementary data:  Supplementary data are available at Bioinformatics online.
Structured sparse canonical correlation analysis for brain imaging genetics: an improved GraphNet method
Authors: Du Lei , Huang Heng , Yan Jingwen , Kim Sungeun , Risacher Shannon L. , Inlow Mark , Moore Jason H. , Saykin Andrew J. , Shen Li ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: February 2016

Motivation: Structured sparse canonical correlation analysis (SCCA) models have been used to identify imaging genetic associations. These models either use group lasso or graph-guided fused lasso to conduct feature selection and feature grouping simultaneously. The group lasso based methods require prior knowledge to define the groups, which limits the capability when prior knowledge is incomplete or unavailable. The graph-guided methods overcome this drawback by using the sample correlation to define the constraint. However, they are sensitive to the sign of the sample correlation, which could introduce undesirable bias if the sign is wrongly estimated.

Results: We introduce a novel SCCA model with a new penalty, and develop an efficient optimization algorithm. Our method has a strong upper bound for the grouping effect for both positively and negatively correlated features. We show that our method performs better than or equally to three competing SCCA models on both synthetic and real data. In particular, our method identifies stronger canonical correlations and better canonical loading patterns, showing its promise for revealing interesting imaging genetic associations.

Availability and implementation: The Matlab code and sample data are freely available at http://www.iu.edu/∼shenlab/tools/angscca/.

Contact:  shenli@iu.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
BCFtools/RoH: a hidden Markov model approach for detecting autozygosity from next-generation sequencing data
Authors: Narasimhan Vagheesh , Danecek Petr , Scally Aylwyn , Xue Yali , Tyler-Smith Chris , Durbin Richard
Published: February 2016

Summary: Runs of homozygosity (RoHs) are genomic stretches of a diploid genome that show identical alleles on both chromosomes. Longer RoHs are unlikely to have arisen by chance but are likely to denote autozygosity, whereby both copies of the genome descend from the same recent ancestor. Early tools to detect RoH used genotype array data, but substantially more information is available from sequencing data. Here, we present and evaluate BCFtools/RoH, an extension to the BCFtools software package, that detects regions of autozygosity in sequencing data, in particular exome data, using a hidden Markov model. By applying it to simulated data and real data from the 1000 Genomes Project we estimate its accuracy and show that it has higher sensitivity and specificity than existing methods under a range of sequencing error rates and levels of autozygosity.

Availability and implementation: BCFtools/RoH and its associated binary/source files are freely available from https://github.com/samtools/BCFtools.

Contact:  vn2@sanger.ac.uk or pd3@sanger.ac.uk

Supplementary information:  Supplementary data are available at Bioinformatics online.
On the discovery of hospital admission patterns—a clarification
Authors: Arandjelović Ognjen
Published: February 2016

Contact:  ognjen.arandjelvoic@gmail.com
Gene expression inference with deep learning
Authors: Chen Yifei , Li Yi , Narayan Rajiv , Subramanian Aravind , Xie Xiaohui
Published: February 2016

Motivation: Large-scale gene expression profiling has been widely used to characterize cellular states in response to various disease conditions, genetic perturbations, etc. Although the cost of whole-genome expression profiles has been dropping steadily, generating a compendium of expression profiling over thousands of samples is still very expensive. Recognizing that gene expressions are often highly correlated, researchers from the NIH LINCS program have developed a cost-effective strategy of profiling only ∼1000 carefully selected landmark genes and relying on computational methods to infer the expression of remaining target genes. However, the computational approach adopted by the LINCS program is currently based on linear regression (LR), limiting its accuracy since it does not capture complex nonlinear relationship between expressions of genes.

Results: We present a deep learning method (abbreviated as D-GEX) to infer the expression of target genes from the expression of landmark genes. We used the microarray-based Gene Expression Omnibus dataset, consisting of 111K expression profiles, to train our model and compare its performance to those from other methods. In terms of mean absolute error averaged across all genes, deep learning significantly outperforms LR with 15.33% relative improvement. A gene-wise comparative analysis shows that deep learning achieves lower error than LR in 99.97% of the target genes. We also tested the performance of our learned model on an independent RNA-Seq-based GTEx dataset, which consists of 2921 expression profiles. Deep learning still outperforms LR with 6.57% relative improvement, and achieves lower error in 81.31% of the target genes.

Availability and implementation: D-GEX is available at https://github.com/uci-cbcl/D-GEX.

Contact:  xhx@ics.uci.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
SplAdder: identification, quantification and testing of alternative splicing events from RNA-Seq data
Authors: Kahles André , Ong Cheng Soon , Zhong Yi , Rätsch Gunnar
Published: February 2016

Motivation: Understanding the occurrence and regulation of alternative splicing (AS) is a key task towards explaining the regulatory processes that shape the complex transcriptomes of higher eukaryotes. With the advent of high-throughput sequencing of RNA (RNA-Seq), the diversity of AS transcripts could be measured at an unprecedented depth. Although the catalog of known AS events has grown ever since, novel transcripts are commonly observed when working with less well annotated organisms, in the context of disease, or within large populations. Whereas an identification of complete transcripts is technically challenging and computationally expensive, focusing on single splicing events as a proxy for transcriptome characteristics is fruitful and sufficient for a wide range of analyses.

Results: We present SplAdder, an alternative splicing toolbox, that takes RNA-Seq alignments and an annotation file as input to (i) augment the annotation based on RNA-Seq evidence, (ii) identify alternative splicing events present in the augmented annotation graph, (iii) quantify and confirm these events based on the RNA-Seq data and (iv) test for significant quantitative differences between samples. Thereby, our main focus lies on performance, accuracy and usability.

Availability: Source code and documentation are available for download at http://github.com/ratschlab/spladder. Example data, introductory information and a small tutorial are accessible via http://bioweb.me/spladder.

Contacts: andre.kahles@ratschlab.org or gunnar.ratsch@ratschlab.org

Supplementary information:  Supplementary data are available at Bioinformatics online.
The Effects of Youth Employment: Evidence from New York City Lotteries
*
Authors: Gelber Alexander , Isen Adam , Kessler Judd B.
Published: February 2016

Programs to encourage labor market activity among youth, including public employment programs and wage subsidies like the Work Opportunity Tax Credit, can be supported by three broad rationales. They may (i) provide contemporaneous income support to participants; (ii) encourage work experience that improves future employment and/or educational outcomes of participants; and/or (iii) keep participants “out of trouble.” We study randomized lotteries for access to the New York City (NYC) Summer Youth Employment Program (SYEP), the largest summer youth employment program in the United States, by merging SYEP administrative data on 294,100 lottery participants to IRS data on the universe of U.S. tax records; to New York State administrative incarceration data; and to NYC administrative cause of death data. In assessing the three rationales, we find that (i) SYEP participation causes average earnings and the probability of employment to increase in the year of program participation, with modest contemporaneous crowdout of other earnings and employment; (ii) SYEP participation causes a modest decrease in average earnings for three years following the program and has no impact on college enrollment; and (iii) SYEP participation decreases the probability of incarceration and decreases the probability of mortality, which has important and potentially pivotal implications for analyzing the net benefits of the program.
Models of human core transcriptional regulatory circuitries
Authors: Saint-André Violaine , Federation Alexander J. , Lin Charles Y. , Abraham Brian J. , Reddy Jessica , Lee Tong Ihn , Bradner James E. , Young Richard A.
Published: February 2016

A small set of core transcription factors (TFs) dominates control of the gene expression program in embryonic stem cells and other well-studied cellular models. These core TFs collectively regulate their own gene expression, thus forming an interconnected auto-regulatory loop that can be considered the core transcriptional regulatory circuitry (CRC) for that cell type. There is limited knowledge of core TFs, and thus models of core regulatory circuitry, for most cell types. We recently discovered that genes encoding known core TFs forming CRCs are driven by super-enhancers, which provides an opportunity to systematically predict CRCs in poorly studied cell types through super-enhancer mapping. Here, we use super-enhancer maps to generate CRC models for 75 human cell and tissue types. These core circuitry models should prove valuable for further investigating cell-type–specific transcriptional regulation in healthy and diseased cells.
The life history of retrocopies illuminates the evolution of new mammalian genes
Authors: Carelli Francesco Nicola , Hayakawa Takashi , Go Yasuhiro , Imai Hiroo , Warnefors Maria , Kaessmann Henrik
Published: February 2016

New genes contribute substantially to adaptive evolutionary innovation, but the functional evolution of new mammalian genes has been little explored at a broad scale. Previous work established mRNA-derived gene duplicates, known as retrocopies, as models for the study of new gene origination. Here we combine mammalian transcriptomic and epigenomic data to unveil the processes underlying the evolution of stripped-down retrocopies into complex new genes. We show that although some robustly expressed retrocopies are transcribed from preexisting promoters, most evolved new promoters from scratch or recruited proto-promoters in their genomic vicinity. In particular, many retrocopy promoters emerged from ancestral enhancers (or bivalent regulatory elements) or are located in CpG islands not associated with other genes. We detected 88–280 selectively preserved retrocopies per mammalian species, illustrating that these mechanisms facilitated the birth of many functional retrogenes during mammalian evolution. The regulatory evolution of originally monoexonic retrocopies was frequently accompanied by exon gain, which facilitated co-option of distant promoters and allowed expression of alternative isoforms. While young retrogenes are often initially expressed in the testis, increased regulatory and structural complexities allowed retrogenes to functionally diversify and evolve somatic organ functions, sometimes as complex as those of their parents. Thus, some retrogenes evolved the capacity to temporarily substitute for their parents during the process of male meiotic X inactivation, while others rendered parental functions superfluous, allowing for parental gene loss. Overall, our reconstruction of the “life history” of mammalian retrogenes highlights retroposition as a general model for understanding new gene birth and functional evolution.
FOXP2 gene deletion and infant feeding difficulties: a case report
Authors: Zimmerman Emily , Maron Jill L.
Published: February 2016

Forkhead box protein P2 (FOXP2) is a well-studied gene known to play an essential role in normal speech development. Deletions in the gene have been shown to result in developmental speech disorders and regulatory disruption of downstream gene targets associated with common forms of language impairments. Despite similarities in motor planning and execution between speech development and oral feeding competence, there have been no reports to date linking deletions within the FOXP2 gene to oral feeding impairments in the newborn. The patient was a nondysmorphic, appropriately and symmetrically grown male infant born at 35-wk gestational age. He had a prolonged neonatal intensive care unit stay because of persistent oral feeding incoordination requiring gastrostomy tube placement. Cardiac and neurological imagings were within normal limits. A microarray analysis found an ∼9-kb loss within chromosome band 7q3.1 that contains exon 2 of FOXP2, demonstrating a single copy of this region instead of the normal two copies per diploid gene. This case study expands our current understanding of the role FOXP2 exerts on motor planning and coordination necessary for both oral feeding success and speech–language development. This case report has important consequences for future diagnosis and treatment for infants with FOXP2 deletions, mutations, and varying levels of gene expression.
Molecular analysis of a male breast cancer patient with prolonged stable disease under mTOR/PI3K inhibitors BEZ235/everolimus
Authors: Brannon A. Rose , Frizziero Melissa , Chen David , Hummel Jennifer , Gallo Jorge , Riester Markus , Patel Parul , Cheung Wing , Morrissey Michael , Carbone Carmine , Cottini Silvia , Tortora Giampaolo , Melisi Davide
Published: February 2016

The mTORC1 inhibitor everolimus (Afinitor/RAD001) has been approved for multiple cancer indications, including ER+/HER2−metastatic breast cancer. However, the combination of everolimus with the dual PI3K/mTOR inhibitor BEZ235 was shown to be more efficacious than either everolimus or BEZ235 alone in preclinical models. Herein, we describe a male breast cancer (MBC) patient who was diagnosed with hormone receptor-positive (HR+)/HER2−stage IIIA invasive ductal carcinoma and sequentially treated with chemoradiotherapy and hormonal therapy. Upon the development of metastases, the patient began a 200 mg twice-daily BEZ235 and 2.5 mg weekly everolimus combination regimen. The patient sustained a prolonged stable disease of 18 mo while undergoing the therapy, before his tumor progressed again. Therefore, we sought to both better understand MBC and investigate the underlying molecular mechanisms of the patient's sensitivity and subsequent resistance to the BEZ235/everolimus combination therapy. Genomic and immunohistochemical analyses were performed on samples collected from the initial invasive ductal carcinoma pretreatment and a metastasis postprogression on the BEZ235/everolimus combination treatment. Both tumors were relatively quiet genomically with no overlap to recurrent MBC alterations in the literature. Markers of PI3K/mTOR pathway hyperactivation were not identified in the pretreatment sample, which complements previous reports of HR+female breast cancers being responsive to mTOR inhibition without this activation. The postprogression sample, however, demonstrated greater than fivefold increased estrogen receptor and pathogenesis-related protein expression, which could have constrained the PI3K/mTOR pathway inhibition by BEZ235/everolimus. Overall, these analyses have augmented the limited episteme on MBC genetics and treatment.
Mutations in the substrate binding glycine-rich loop of the mitochondrial processing peptidase-α protein (PMPCA) cause a severe mitochondrial disease
Authors: Joshi Mugdha , Anselm Irina , Shi Jiahai , Bale Tejus A. , Towne Meghan , Schmitz-Abe Klaus , Crowley Laura , Giani Felix C. , Kazerounian Shideh , Markianos Kyriacos , Lidov Hart G. , Folkerth Rebecca , Sankaran Vijay G. , Agrawal Pankaj B.
Published: February 2016

We describe a large Lebanese family with two affected members, a young female proband and her male cousin, who had multisystem involvement including profound global developmental delay, severe hypotonia and weakness, respiratory insufficiency, blindness, and lactic acidemia—findings consistent with an underlying mitochondrial disorder. Whole-exome sequencing was performed on DNA from the proband and both parents. The proband and her cousin carried compound heterozygous mutations in thePMPCAgene that encodes for α-mitochondrial processing peptidase (α-MPP), a protein likely involved in the processing of mitochondrial proteins. The variants were located close to and postulated to affect the substrate binding glycine-rich loop of the α-MPP protein. Functional assays including immunofluorescence and western blot analysis on patient's fibroblasts revealed that these variants reduced α-MPP levels and impaired frataxin production and processing. We further determined that those defects could be rescued through the expression of exogenous wild-typePMPCAcDNA. Our findings link defective α-MPP protein to a severe mitochondrial disease.
Discovery of a potentially deleterious variant in TMEM87B in a patient with a hemizygous 2q13 microdeletion suggests a recessive condition characterized by congenital heart disease and restrictive cardiomyopathy
Authors: Yu Hung-Chun , Coughlin Curtis R. , Geiger Elizabeth A. , Salvador Blake J. , Elias Ellen R. , Cavanaugh Jean L. , Chatfield Kathryn C. , Miyamoto Shelley D. , Shaikh Tamim H.
Published: February 2016

Restrictive cardiomyopathy (RCM) is a rare cause of heart muscle disease with the highest mortality rate among cardiomyopathy types. The etiology of RCM is poorly understood, although genetic causes have been implicated, and syndromic associations have been described. Here, we describe a patient with an atrial septal defect and restrictive cardiomyopathy along with craniofacial anomalies and intellectual disabilities. Initial screening using chromosomal microarray analysis (CMA) identified a maternally inherited 2q13 microdeletion. The patient had many of the features reported in previous cases with the recurrent 2q13 microdeletion syndrome. However, the inheritance of the microdeletion from an unaffected mother combined with the low incidence (10%) and milder forms of cardiac defects in previously reported cases made the clinical significance of the CMA results unclear. Whole-exome sequencing (WES) with trio-based analysis was performed and identified a paternally inherited TMEM87B mutation (c.1366A>G, p.Asn456Asp) in the patient. TMEM87B, a highly conserved, transmembrane protein of currently unknown function, lies within the critical region of the recurrent 2q13 microdeletion syndrome. Furthermore, a recent study had demonstrated that depletion of TMEM87B in zebrafish embryos affected cardiac development and led to cardiac hypoplasia. Thus, by combining CMA and WES, we potentially uncover an autosomal-recessive disorder characterized by a severe cardiac phenotype caused by mutations in TMEM87B. This study expands the spectrum of phenotypes associated with the recurrent 2q13 microdeletion syndrome and also further suggests the role of TMEM87B in its etiology, especially the cardiac pathology.
Boron carbide composite apertures for small-angle neutron scattering made by three-dimensional printing
Authors: Olsson Anders , Rennie Adrian R.
Published: February 2016

Apertures for small-angle neutron scattering prepared from a boron carbide/polymer composite have been made by three-dimensional printing using fused filament fabrication. Use of enriched 10B4C gives higher absorption and much lower parasitic scattering than natural B4C. The simple fabrication, the capability to replace toxic and environmentally hazardous materials such as cadmium, and the possibility to diminish the secondary background of γ-radiation are attractive features of use of these materials. Complex shapes, apart from apertures, can be fabricated readily with this composite, for example, to make shielding for instrument components and masks used to calibrate detectors.
EDP2XRD: a computer program for converting electron diffraction patterns into X-ray diffraction patterns
Authors: Liu Hongwei , Foley Matthew , Lin Qingyun , Liu Jiangwen
Published: February 2016

Mny commercial software packages for X-ray diffraction pattern analysis are capable of identifying multiple phases in bulk materials. However, X-ray diffraction patterns cannot record those phases with very small volume ratio or non-homogeneous distribution, which may mean that researchers have to use instead electron diffraction patterns from a very small region of interest.EDP2XRD, a new program for converting electron diffraction patterns into X-ray diffraction patterns, is described here. The program has been developed in order to utilize X-ray analysis software for electron diffraction patterns taken from mixed-phase nanocrystalline materials with a transmission electron microscope. It is specifically designed for material researchers who are engaged in crystallographic microstructure analysis. The difference from other popular commercial software for crystallography is that this program provides new options to convert and plot X-ray diffraction patterns for arbitrary electron diffraction rings and to process raw images to enhance conversion performance. The program contains the necessary crystallographic calculator to list planardspacings and corresponding X-ray diffraction angles.
Undertaking individual transdisciplinary PhD research for sustainable development
Authors: van Breda John , Musango Josephine , Brent Alan
Published: February 2016

Purpose

– This paper aims to improve the understanding of individual transdisciplinary PhD research in a developing country context, focusing on three individual PhD case studies in South Africa.

Design/methodology/approach

– Multiple-case method was used, and three completed transdisciplinary PhD research efforts undertaken at the Stellenbosch University were selected. They were coordinated through the TsamaHub, an inter-faculty platform at the University which organises educational modules for transdisciplinary research. Using actual research experiences and reflections of the three individual PhDs, the paper evaluates their work in terms of ontological, epistemological, methodological and methodical/methods aspects.

Findings

– The central challenge to individual PhD researchers is engagement with non-academic actors to enable joint problem formulation, analysis and transformation. To overcome this, the paper suggests that developing individual epistemic relationships to build “transdisciplinary epistemic communities” should be considered for inclusion as an intentional aspect of transdisciplinary research design.

Research limitations/implications

– “Transdisciplinary epistemic communities” is still a concept in its infancy and needs more work before it may be theoretically and practically useful.

Practical implications

– Continuously guiding the individual transdisciplinary research process in a reflexive, recursive, transparent and equal manner is absolutely critical because transdisciplinary research cannot be done successfully if dominated by overly methods-driven approaches.

Originality/value

– The discourse around transdisciplinary methodology has major implications for the design of individual PhD research. The paper provides recommendations to enhance the theory and practice of individual transdisciplinary PhD research.
Data networks and sustainability education in African universities
Authors: Bothun Gregory D
Published: February 2016

Purpose

– The purpose of this paper is to provide a case study report of the development of data networks and initial connectivity in the Sub-Saharan African (SSA) region and how that development evolved into the formation of research and education (R
&
E) networks that enable new collaborations and curriculum potential.

Design/methodology/approach

– This case study is presented through the past 20 year’s operations and field activities of the Network Startup Resource Center (NSRC) at the University of Oregon, who in partnership with the National Science Foundation has worked together to significantly train network engineers in Africa on how to develop regional R
&
E networks that can link together the various research universities in SSA.

Findings

– The author shows how the development of these networks have fostered improved collaboration between African and US scientists, particularly around issues that relate to climate change. This paper contains testimonials from both scientists and on-the-ground key directors in Africa about the value of these improved networks. The expansion of regional R
&
E networks has allowed the Association of African Universities (AAU) to launch sustainable development as one of its new core programs over the period 2013-2017. Within this new core AAU program are four sub-themes: agriculture and food security, water resources management, climate change and energy. All of these themes will benefit directly from these new, network-enabled, data-sharing abilities.

Practical implications

– The current state of network-driven curriculum and curriculum exchange between African universities is assessed and compared that to that in the early days of academic network penetration (1990-2000) in the USA to find similar rates of evolution. Since 2015, SSA has sufficient network access and connectivity to now enable a wide variety of new collaborative research and collaborative academic programs.

Originality/value

– The experience and operational competence of the NSRC at the University of Oregon needs to be detailed and espoused. No other American university has had such an impact on Africa in terms of improving its overall network infrastructure enabling new kinds of collaborative research on real-world problems, such as climate change and resource depletion in Africa.
Cigarette advertising in Cold War Bulgaria
Authors: Neuburger Mary Catherine
Published: February 2016

Purpose

– This paper aims to explore the parameters of Bulgarian cigarette advertising in the Cold War period. It contrasts the evolution of cigarette marketing in Bulgaria and the USA in the context of contrasting communist and capitalist notions of the “good life” versus the “common good”.

Design/methodology/approach

– The paper is informed by a growing literature on advertising under communism, but also new work on consumption in the Soviet Union and Cold War Eastern Europe. It draws upon archival and printed Bulgarian, and some American, sources, and the memoir of a key player in the Bulgarian tobacco industry.

Findings

– The paper concludes that marketing of cigarettes in communist Bulgaria gained momentum in the same period that cigarette advertising in the USA was severely curtailed. In Bulgaria, the notion that cigarettes were key to the promised “good life” and “building socialism”, out-weighed any notion of harm to the “common good”.

Originality/value

– This study casts doubt on the common notion that there was no advertising under communism, by offering an in-depth study of an industry that was allowed to market and develop a quality product to an unusual degree. It undermines assumptions about “command” economy, industry behavior, contributing to a re-thinking of Eastern Bloc consumer culture. In addition, it sheds light on changes in the acceptability of cigarette advertising within the Cold War context, namely, how the process of advertising regulation in the West, and increased marketing in the East, fit into Cold War debates and interactions.
The fashion gap: the Cold War politics of American and Soviet fashion, 1945-1959
Authors: Amerian Stephanie M.
Published: February 2016

Purpose

– The purpose of this paper is to examine the role that fashion played in the Cold War competition between the USA and the Soviet Union during the period from 1945 to 1959.

Design/methodology/approach

– This paper begins by situating fashion within the larger American efforts of cultural diplomacy. It then examines the American and Soviet approaches to fashion. Finally, it focuses on the fashion show at the 1959 American National Exhibition in Moscow. This paper utilizes primary sources, including archival sources and period newspapers and magazines.

Findings

– Both American and Soviet leaders tried to use fashion to embody the ideological values of each political and economic system. Both also acknowledged a “fashion gap”, whereby Americans enjoyed clear superiority thanks to a well-developed mass production system of ready-made, stylish clothing, that some termed the American Look. Americans hoped the fashion gap would demonstrate that only capitalism could provide women with an abundance of the necessary – but also desirable – consumer goods that enhanced their feminine beauty. Thus, fashion played an important part in the Cold War cultural struggle, in which American and Soviet women were key participants.

Originality/value

– Much has been written about the Cold War cultural diplomacy, especially the Moscow exhibition, but fashion is often left out of the analyses. Meanwhile, both the American Look and Soviet efforts to create socialist fashion have been examined, but no work has been done to look at the two together to understand fashion’s larger implications for the Cold War.
Forgotten classics:Advertising in a Free Society, by Ralph Harris and Arthur Seldon (1959)
Authors: Pressey Andrew D
Published: February 2016

Purpose

– The purpose of this paper is to reviewAdvertising in a Free Society– a defence of the advertising industry – by Ralph Harris and Arthur Seldon, and to evaluate its status as a justifiable forgotten classic of the marketing literature.

Design/Methodology/Approach

–Advertising in a Free Societyis placed in historical context (the Cold War), summarised and reviewed.

Findings

– During the 1950s, as the UK experienced a period of affluence and growing consumerism, the advertising industry was again subject to the criticisms that had been levelled at it by influential scholars in the late nineteenth and early twentieth centuries. Against this context,Advertising in a Free Societydeserves to be remembered as one of the earliest defences of advertising and remains highly relevant. Harris and Seldon were leading figures in the Institute of Economic Affairs (IEA), joining shortly after its inception, which became an influential group both in the UK and abroad, influencing policy on free markets.

Originality/Value

– AlthoughAdvertising in a Free Societyattracted few citations (going out of print between its publication in 1959 and 2014 when it was republished by the IEA), and largely forgotten by marketing scholars, it provides a significant source for marketing historians interested in advertising criticism, the growth of the British advertising industry and the role of advertising in democratic societies. A reanalysis of the text situated in its historical context – the height of the Cold War – reveals that the text can be viewed as an artefact of the conflict, deploying the rhetoric of the period in defending the advertising industry and highlighting the positive role that advertising could make in free societies.
Eosinophilic pustular folliculitis: A published work‐based comprehensive analysis of therapeutic responsiveness
Authors: Nomura Takashi , Katoh Mayumi , Yamamoto Yosuke , Miyachi Yoshiki , Kabashima Kenji
Published: February 2016

Eosinophilic pustular folliculitis (EPF) is a non‐infectious inflammatory dermatosis of unknown etiology that principally affects the hair follicles. There are three variants of EPF: (i) classic EPF; (ii) immunosuppression‐associated EPF, which is subdivided into HIV‐associated (IS/HIV) and non‐HIV‐associated (IS/non‐HIV); and (iii) infancy‐associated EPF. Oral indomethacin is efficacious, especially for classic EPF. No comprehensive information on the efficacies of other medical management regimens is currently available. In this study, we surveyed regimens for EPF that were described in articles published between 1965 and 2013. In total, there were 1171 regimens; 874, 137, 45 and 115 of which were applied to classic, IS/HIV, IS/non‐HIV and infancy‐associated EPF, respectively. Classic EPF was preferentially treated with oral indomethacin with efficacy of 84% whereas topical steroids were preferred for IS/HIV, IS/non‐HIV and infancy‐associated EPF with efficacy of 47%, 73% and 82%, respectively. Other regimens such as oral Sairei‐to (a Chinese–Japanese herbal medicine), diaminodiphenyl sulfone, cyclosporin and topical tacrolimus were effective for indomethacin‐resistant cases. Although the preclusion of direct comparison among cases was one limitation, this study provides a dataset that is applicable to the construction of therapeutic algorithms for EPF.
Angiotensin receptor‐1A knockout leads to hydronephrosis not associated with a loss of pyeloureteric peristalsis in the mouse renal pelvis
Authors: Nguyen Michael J , Hashitani Hikaru , Lang Richard J
Published: February 2016

The action of angiotensin II (AngII) on the Ca2+ signals driving pyeloureteric peristalsis was investigated using both conventional and angiotensin receptor (ATr) ATr1A and ATr2 knockout (−/−) mice. Contractility in the renal pelvis of adult ATr1A−/− and ATr2−/− mice was compared to their respective wildtype (ATr1A+/+ and ATr2+/+) controls of the same genetic background (FVB/N and C57Bl/6 respectively) using video microscopy. The effects of AngII on the Ca2+ signals in typical and atypical smooth muscle cells (TSMCs and ASMCs, respectively) within the pelvic wall of conventional mice were recorded using Fluo‐4 Ca2+ imaging. Compared to ATr1A+/+, ATr2+/+ and ATr2−/− mice, kidneys of the ATr1A−/− mouse were mildly‐to‐severely hydronephrotic, associated with an enlarged calyx, an atrophic papilla and a hypoplastic renal pelvis. Contraction frequencies in the renal pelvis of moderately hydronephrotic ATr1A−/− and unaffected ATr2−/− mice were not significantly different from their ATr1A+/+, ATr2+/+ controls. No contractions were observed in severely‐hydronephrotic ATr1A−/− kidneys. AngII increased the spontaneous contraction frequency of the renal pelvis in ATr1A+/+, ATr2+/+ and ATr2−/− mice, but had little effect on the contractions in the mildly‐hydronephrotic ATr1A−/− renal pelvis. The ATr1 blocker, candesartan prevented the positive chronotropic effects of AngII. AngII increased the frequency and synchronicity of Ca2+ transients in both TSMCs and ASMCs. It was concluded that the hydronephrosis observed in ATr1A−/− mouse kidneys does not arise from a failure in the development of the essential pacemaker and contractile machinery driving pyeloureteric peristalsis.
The unaccountable risks of LIBOR
Authors: Bryan Dick , Rafferty Michael
Published: February 2016

One of the on‐going consequences of recent financial crises seems to be that the conventional ‘anchor’ measures of global finance (such as the US dollar, treasury bonds and AAA rated securities) are no longer playing the anchoring role once believed of them. LIBOR now needs to be added to this list and not just because it has been tarnished by illegal practices, but because it is looking increasingly surpassed by financial market practices. LIBOR was believed to provide a risk‐free rate of interest, but has been revealed to be risk‐laden. Moreover, LIBOR is a measure of the costs of borrowing, whilst market concern is increasingly with measures of interest rate volatility.

This paper looks at why, in the context of crisis, financial market focus on interest rates is turning towards other benchmarks, notably the overnight indexed swap (OIS) market, and what this shift might be telling us about the anchoring requirements of global financial markets.
Party competition over decentralisation: The influence of ideology and electoral incentives on issue emphasis
Authors: TOUBEAU SIMON , WAGNER MARKUS
Published: February 2016

Under what conditions is decentralisation a salient issue for state‐wide political parties? It is argued in this article that the extent to which state‐wide parties emphasise decentralisation depends on their strategic considerations: on their overall ideology, on the electoral incentives created by the context in which they compete, and on the interaction between the two. The results of the analysis of party manifestos in 31 countries since 1945 are as follows. First, parties that pay greater attention to cultural matters relative to economic matters tend to talk more about decentralisation. Second, the systemic salience of decentralisation also encourages parties to talk more about decentralisation. Third, the larger the regionally based ethnic groups within a country, the more salience all state‐wide political parties will attach to decentralisation. Finally, only parties that put greater relative emphasis on cultural matters tend to respond to the electoral threat of regionalist parties. The influence of territorial diversity on the salience of decentralisation thus works through two channels and is partly conditioned by political parties’ ideological profile.