bluuebunny/crossref_metadata_2025 huggingface dataset:
RNA-Seq and Protein Mass Spectrometry in Microdissected Kidney Tubules Reveal Signaling Processes that Initiate Lithium-Induced Diabetes Insipidus
Authors: Sung Chih-Chien , Chen Lihe , Limbutara Kavee , Jung Hyun Jun , Gilmer Gabrielle G. , Yang Chin-Rang , Khositseth Sookkasem , Lin Shih-Hua , Chou Chung-Lin , Knepper Mark A.
Published: July 2018

ABSTRACT1

Lithium salts, used for treatment of bipolar disorder, frequently induce nephrogenic diabetes insipidus (NDI), limiting therapeutic success. NDI is associated with loss of expression of the molecular water channel, aquaporin-2, in the renal collecting duct (CD). Here, we use the methods of systems biology in a well-established rat model of lithium-induced NDI to identify signaling pathways activated at the onset of polyuria. Using single-tubule RNA-Seq, full transcriptomes were determined in microdissected cortical CDs of rats 72 hrs after initiation of lithium chloride (LiCl) administration (vs. time-controls without LiCl). Transcriptome-wide changes in mRNA abundances were mapped to gene sets associated with curated canonical signaling pathways, showing evidence for activation of NF-κB signaling with induction of genes coding for multiple chemokines as well as most components of the Major Histocompatibility Complex (MHC) Class I antigen-presenting complex. Administration of antiinflammatory doses of dexamethasone to LiCl-treated rats countered the loss of aquaporin-2 protein. RNA-Seq also confirmed prior evidence of a shift from quiescence into the cell cycle with arrest. Time course studies demonstrated an early (12 hrs) increase in multiple immediate early genes including several transcription factors. Protein mass spectrometry in microdissected cortical CDs provided corroborative evidence but also identified decreased abundance of several anti-oxidant proteins. Integration of new data with prior data about lithium effects at a molecular level leads to a signaling model in which lithium increases ERK activation leading to induction of NF-κB signaling and an inflammatory-like response that represses Aqp2 gene transcription.
Characterizing drug resistance using geometric ensembles from HIV protease dynamics
Authors: Sheik Amamuddy Olivier , Bishop Nigel T , Tastan Bishop Ozlem
Published: July 2018

The use of antiretrovirals (ARVs) has drastically improved the life quality and expectancy of HIV patients since their introduction in health care. Several millions are still afflicted worldwide by HIV and ARV resistance is a constant concern for both healthcare practitioners and patients, as while treatment options are finite, the virus constantly adapts and selects for resistant viral strains under the pressure of drug treatment. The HIV protease is a crucial enzyme that processes viral polyproteins into their functional form, and has been a game changing drug target since the first application. Due to similarities in protease inhibitor designs, drug cross-resistance is not uncommon across ARVs of the same class. It is known that resistance against protease inhibitors is associated with a wider active site, but results from our large scale molecular dynamics analysis further show, for the first time, that there are regions of local expansions and compactions associated with high levels of resistance conserved across eight different protease inhibitors visible in their complexed form in closed receptor conformations. The method developed here is novel, supplementary to the methods of nonsynonymous mutation analysis, and should be applicable in analyzing the structural consequences of mutations in other contexts.
Explaining Visual Cortex Phenomena using Recursive Cortical Network
Authors: Lavin Alexander , Guntupalli J. Swaroop , Lázaro-Gredilla Miguel , Lehrach Wolfgang , George Dileep
Published: July 2018

The connectivity and information pathways of visual cortex are well studied, as are observed physiological phenomena, yet a cohesive model for explaining visual cortex processes remains an open problem. For a comprehensive understanding, we need to build models of the visual cortex that are capable of robust real-world performance, while also being able to explain psychophysical and physiological observations. To this end, we demonstrate how the Recursive Cortical Network (George et al., 2017) can be used as a computational model to reproduce and explain subjective contours, neon color spreading, occlusion vs. deletion, and the border-ownership competition phenomena observed in the visual cortex.
Tensor decomposition–based unsupervised feature extraction for integrated analysis of TCGA data on microRNA expression and promoter methylation of genes in ovarian cancer
Authors: Taguchi Y-h. , Ng Ka-Lok
Published: July 2018

Integrated analysis of epigenetic profiles is important but difficult. Tensor decomposition–based unsupervised feature extraction was applied here to data on microRNA (miRNA) expression and promoter methylation of genes in ovarian cancer. It selected seven miRNAs and 241 genes by expression levels and promoter methylation degrees, respectively, such that they showed differences between eight normal ovarian tissue samples and 569 tumor samples. The expression levels of the seven miRNAs and the degrees of promoter methylation of the 241 genes also correlated significantly. Conventional Student’sttest–based feature selection failed to identify miRNAs and genes that have the above properties. On the other hand, biological evaluation of the seven identified miRNAs and 241 identified genes suggests that they are strongly related to cancer as expected.
A practical guide to linking brain-wide gene expression and neuroimaging data
Authors: Arnatkevičiūtė Aurina , Fulcher Ben D. , Fornito Alex
Published: July 2018

The recent availability of comprehensive, brain-wide gene expression atlases such as the Allen Human Brain Atlas (AHBA) has opened new opportunities for understanding how spatial variations on the molecular scale relate to the macroscopic neuroimaging phenotypes. A rapidly growing body of literature is demonstrating relationships between gene expression and diverse properties of brain structure and function, but approaches for combining expression atlas data with neuroimaging are highly inconsistent, with substantial variations in how the expression data are processed. The degree to which these methodological variations affect findings is unclear. Here, we outline a seven-step analysis pipeline for relating brain-wide transcriptomic and neuroimaging data and compare how different processing choices influence the resulting data. We suggest that studies using AHBA should work towards a unified data processing pipeline to ensure consistent and reproducible results in this burgeoning field.
Oncogenic effects of germline mutations in lysosomal storage disease genes
Authors: Shin Junghoon , Kim Daeyoon , Kim Hyung-Lae , Choi Murim , Korbel Jan O. , Yoon Sung-Soo , Koh Youngil ,   on behalf of the PCAWG Germline Cancer Genome Working Group and the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Network
Published: July 2018

Clinical observations have indicated that patients with Gaucher disease or Fabry disease are at increased risk of cancer. However, a systematic evaluation of the oncogenic effects of causal mutations of lysosomal storage diseases (LSDs) has been lacking. Here we report a comprehensive association analysis between potentially pathogenic germline mutations in LSD genes and cancer interrogating genomic (or exomic) variant datasets derived from the Pan-Cancer Analysis of Whole Genomes project (case cohort), the 1000 Genomes project (primary control cohort), and the Exome Aggregation Consortium that does not include The Cancer Genome Atlas subset (validation control cohort). We show that potentially pathogenic variants (PPVs) in 42 LSD genes are significantly enriched in cancer patients in a histology-dependent manner, cancer risk is higher in individuals with a greater number of PPVs, and cancer develops earlier in PPV carriers. Analysis of tumor genomic and transcriptomic data from the pancreatic adenocarcinoma cohort revealed potential mechanisms that might be involved in the oncogenic contribution of PPVs. Our findings extend the mechanistic understanding of inherited cancer susceptibility and highlight the promise of harnessing available therapeutic strategies to restore lysosomal function for personalized cancer prevention.
Mitochondrial acetyl-CoA reversibly regulates locus-specific histone acetylation and gene expression
Authors: Lozoya Oswaldo A. , Wang Tianyuan , Grenet Dagoberto , Wolfgang Taylor C. , Sobhany Mack , da Silva Douglas Ganini , Riadi Gonzalo , Chandel Navdeep , Woychik Richard P. , Santos Janine H.
Published: July 2018

The impact of mitochondria in epigenetics is emerging but our understanding of this relationship and its impact on gene expression remain incomplete. We previously showed that acute mitochondrial DNA (mtDNA) loss leads to histone hypoacetylation. It remains to be defined if these changes are maintained when mitochondrial dysfunction is chronic and, importantly, if they are sufficient to alter gene expression. To fill these gaps, we here studied both a progressive and a chronic model of mtDNA depletion using biochemical, pharmacological, genomics and genetic assays. We show that histones are hypoacetylated in both models. We link these effects to decreased histone acetyltransferase (HAT) activity independent of changes in ATP citrate lyase function, which can be reversibly modulated by altering specifically the mitochondrial pool of acetyl-CoA. Also, we determined that these changes regulate locus-specific gene expression and physiological outcomes, including the production of prostaglandins. These results may be relevant to the pathophysiology of mtDNA depletion syndromes and to understanding the effects of environmental agents, such as AZT or antibiotics, that lead to physical or functional mtDNA loss.
Phosphatidylinositol 4,5-Bisphosphate (PIP2) Regulates KCNQ3 K+ Channels through Multiple Sites of Action
Authors: Choveau Frank S. , La Rosa Victor De , Bierbower Sonya M. , Hernandez Ciria C. , Shapiro Mark S.
Published: July 2018

Phosphatidylinositol 4,5-bisphosphate (PIP2) regulates the function of many ion channels, including M-type (KCNQ1-5, Kv7) K+ channels; however the molecular mechanisms involved in this regulation remain unclear. To identify the sites of action on KCNQ3 channels, we used as our baseline the A315T pore mutant (KCNQ3T) that increases channel currents without modifying the apparent affinity of PIP2 and performed extensive mutagenesis in regions that have been suggested to be involved in PIP2 interactions among the KCNQ family. Using the zebrafish (Danio rerio) voltage-sensitive phosphatase to deplete PIP2 as a probe for apparent affinity of the channels, we found that PIP2 modulates KCNQ channel function through four different domains. 1) the A-B helix linker that we previously identified as important for both KCNQ2 and KCNQ3, 2) the junction between S6 and the A helix (S6Jx), 3) the S2-S3 linker and 4) the S4-S5 linker. We found that PIP2 interactions within these domains were not coupled to the voltage dependence of activation. Extensive homology modeling and docking simulations between the wild-type or mutant KCNQ3 channels and PIP2, correlated with the experimental data. Our results indicate that PIP2 modulates KCNQ3 channel function by interacting synergistically with a minimum of four cytoplasmic domains.
Live tracking of inter-organ communication by endogenous exosomes in vivo
Authors: Verweij Frederik J , Revenu Celine , Arras Guillaume , Dingli Florent , Loew Damarys , Follain Gautier , Allio Guillaume , Goetz Jacky G. , Herbomel Philippe , Bene Filippo Del , Raposo Graça , van Niel Guillaume
Published: July 2018

Extracellular vesicles (EVs) are released by most cell types but the definitive demonstration of their functional relevance remains challenging due to the lack of appropriate model organisms. Here we developed anin vivomodel to study EV physiology by expressing CD63-pHluorin in zebrafish embryos. A combination of microscopy techniques and proteomic analysis allowed us to study the biogenesis, composition, transfer, uptake and fate of individual endogenous EVsin vivo. We identified an exosome population released in a syntenin-dependent manner from the Yolk Syncytial Layer into the blood circulation. These exosomes were specifically captured, endocytosed and degraded by patrolling macrophages and endothelial cells in the Caudal Vein Plexus (CVP) in a scavenger receptor and dynamin-dependent manner. Interference with exosome secretion affected CVP growth, supporting their trophic role. Altogether, our work provides a unique model to track in vivo inter-organ communication by endogenous exosomes at individual vesicle level and high spatio-temporal accuracy.

Highlights

- Single endogenous EVs can be live-visualized in the whole embryo with CD63-pHluorin

- In the YSL, syntenin regulates exosome release into the blood for their propagation

- YSL exosomes reach the tail to be taken up by macrophages and endothelial cells

- Uptake is scavenger receptor and dynamin-dependent and provides trophic support

Blurb

We propose zebrafish embryos expressing a fluorescent reporter for exosomes as a relevant model organism to live-track production, journey and fate of individual extracellular vesicles in vivo. Our model allows investigation of the composition of EVs and the molecular mechanisms controlling their biogenesis and fate and functions in receiving cells.
Damage-induced reactive oxygen species enable zebrafish tail regeneration by repositioning of Hedgehog expressing cells
Authors: Romero Maria Montserrat Garcia , McCathie Gareth , Jankun Philip , Roehl Henry Hamilton
Published: July 2018

Aquatic vertebrates have a remarkable ability to regenerate limbs and tails after amputation. Previous studies indicate that reactive oxygen species (ROS) signaling initiates regeneration, but the mechanism by which this takes place is poorly understood. Developmental signalling pathways have been shown to have pro-regenerative roles in many systems. However, whether these are playing roles that are specific to regeneration, or are simply recapitulating their developmental functions is unclear. We have analysed zebrafish larval tail regeneration and find evidence that ROS released upon wounding cause repositioning of notochord cells to the damage site. These cells secrete Hedgehog ligands which are required for regeneration. Hedgehog signalling is not required for normal tail development suggesting that it has a regeneration specific role. Our results provide a model for how ROS initiate tail regeneration, and indicate that developmental signaling pathways can play regenerative functions that are not directly related to their developmental roles.
Pannexin-1 mediated ATP release in adipocytes is sensitive to glucose and insulin and modulates lipolysis and macrophage migration
Authors: Tozzi Marco , Hansen Jacob B. , Novak Ivana
Published: July 2018

One-sentence summary

Insulin inhibits ATP release in adipocytes

Extracellular ATP signaling is involved in many physiological and pathophysiological processes, and purinergic receptors are targets for drug therapy in several diseases, including obesity and diabetes. Adipose tissue has crucial functions in lipid and glucose metabolism and adipocytes express purinergic receptors. However, the sources of extracellular ATP in adipose tissue are not yet characterized.

Here, we show that upon adrenergic stimulation white adipocytes release ATP through the pannexin-1 pore that is regulated by a cAMP-PKA dependent pathway. The ATP release correlates with increased cell metabolism, and extracellular ATP induces Ca2+ signaling and lipolysis in adipocytes and promotes macrophages migration. Most importantly, ATP release is markedly inhibited by insulin, and thereby auto/paracrine purinergic signaling in adipose tissue would be attenuated. Furthermore, we define the signaling pathway for insulin regulated ATP release.

Our findings reveal the insulin-pannexin-1-purinergic signaling cross-talk in adipose tissue and we propose that deregulation of this signaling may underlie adipose tissue inflammation and type-2 diabetes.
Natural selection onTMPRSS6associated with the blunted erythropoiesis and improved blood viscosity in Tibetan Pigs
Authors: Kong Xiaoyan , Dong Xinxing , Yang Shuli , Qian Jinhua , Yang Jianfa , Jiang Qiang , Li Xingrun , Wang Bo , Yan Dawei , Lu Shaoxiong , Mao Huaming , Gou Xiao
Published: July 2018

Tibetan pigs, indigenous to Tibetan plateau, are well adapted to hypoxia. So far, there have been not any definitively described genes and functional sites responsible for hypoxia adaptation for the Tibetan pig. Here we conducted resequencing of the nearly entire genomic region (40.1 kb) of the candidate geneTMPRSS6(Transmembrane protease, serine 6) associated with hemoglobin concentration (HGB) and red blood cell count (RBC) in 40 domestic pigs and 40 wild boars from five altitudes along the Tea-horse ancient road and identified 708 SNPs, in addition to an indel (CGTG/----) in the intron 10. Both the CGTG deletion frequency and the pairwise r2linkage disequilibrium showed an increase with elevated altitudes in 838 domestic pigs from five altitudes, suggesting thatTMPRSS6has been under Darwinian positive selection. As the conserved core sequence of hypoxia-response elements (HREs), the deletion of CGTG in Tibetan pigs decreased the expression levels ofTMPRSS6mRNA and protein in the liver revealed by real-time quantitative PCR and western blot, respectively. To explore whether reducedTMPRSS6expression level could improve blood viscosity, the relationship between CGTG indel and hematologic and hemorheologic parameters in 482 domestic pigs from continuous altitudes was detected and dissected a genetic effect on reducing HGB by 13.25g/L in Gongbo’gyamda Tibetan pigs and decreasing MCV by 4.79 fl in Diqing Tibetan pigs. In conclusion, the CGTG deletion ofTMPRSS6resulted in lower HGB and smaller MCV, thereby blunting erythropoiesis and improving blood viscosity as well as erythrocyte deformability.
How do citizens perceive farm animal welfare conditions in Brazil?
Authors: de Queiroz Ricardo Guimarães , de Faria Domingues Carla Heloisa , Canozzi Maria Eugênia Andrighetto , Garcia Rodrigo Garófallo , Ruviaro Clandio Favarini , Barcellos Júlio Otávio Jardim , Borges João Augusto Rossi
Published: July 2018

The aim of this study is to understand the perceptions of Brazilian citizens about the actual conditions of farm animal welfare in the poultry, beef, and dairy supply chains. To reach this aim, an online survey was conducted. The analysis was based on descriptive statistics and three logistic regressions models. Results of descriptive statistics showed that citizens in Brazil had mostly negative perceptions about the actual conditions of animal welfare in the poultry, beef, and dairy supply chains. Results of the logistic regression models showed that in the poultry and dairy supply chains, citizens with background in agricultural/veterinary sciences, and citizens who reported a higher level of knowledge about these supply chains, were more likely to perceive as bad the actual conditions of farm animal welfare. In the poultry supply chain, citizens who reported previous contact with poultry farms were also more likely to perceive as bad the actual condition of farm animal welfare. In addition, the perception that farmers are mainly focused on the economic aspect of farming and less on animal welfare, the perception that animals do not have a good quality of life while housed on farms, and the perception that animals are not adequately transported and slaughtered, negatively impact on perceptions about the actual conditions of farm animal welfare in the three supply chains. We concluded that a protocol aimed to improve citizens’ perceptions about the actual conditions of farm animal welfare should focus in all phases of the supply chains.
The tumor suppressor p53 promotes carcinoma invasion and collective cellular migration
Authors: He Shijie , Carman Christopher V. , Lee Jung Hyun , Lan Bo , Koehler Stephan , Atia Lior , Park Chan Young , Kim Jae Hun , Mitchel Jennifer A. , Park Jin-Ah , Butler James P. , Lee Sam W. , Fredberg Jeffrey J.
Published: July 2018

Loss of function of the tumor suppressor p53 is generally thought to increase cell motility and invasiveness. Using 2-D confluent and 3-D spheroidal cell motility assays with bladder carcinoma cells and colorectal carcinoma cells, we report, to the contrary, that loss of p53 can decrease cell motility and invasion.

For migration of the single cell studied in isolation, loss of function of the tumor suppressor p53 is thought to increase cell motility. Here by contrast we used the 2-D confluent cell layer and the 3-D multicellular spheroid to investigate how p53 impacts dissemination and invasion of cellular collectives. We used two human carcinoma cell lines, the bladder carcinoma EJ and the colorectal carcinoma HCT116. We began by replicating single cell invasion in the traditional Boyden chamber assay, and found that the number of invading cells increased with loss of p53, as expected. In the confluent 2-D cell layer, however, for both EJ and HCT, speeds and effective diffusion coefficients for the p53 null types compared to their p53 expressing counterparts were significantly smaller. Compared to p53 expressers, p53 null cells exhibited more organized cortical actin rings together with reduced front-rear cell polarity. Furthermore, loss of p53 caused cells to exert smaller traction forces upon their substrates, and reduced formation of cryptic lamellipodia. In a 3-D collagen matrix, p53 consistently promoted invasion of the multicellular spheroids into surrounding matrix. Together, these results show that p53 expression in these carcinoma model systems increases collective cellular migration and invasion. As such, these studies point to paradoxical contributions of p53 in single cell versus collective cellular migration.
Stress response, behavior, and development are shaped by transposable element-induced mutations in Drosophila
Authors: Rech Gabriel E. , Bogaerts-Marquez Maria , Barrón Maite G. , Merenciano Miriam , Villanueva-Cañas José Luis , Horváth Vivien , Fiston-Lavier Anna-Sophie , Luyten Isabelle , Venkataram Sandeep , Quesneville Hadi , Petrov Dmitri A. , González Josefa
Published: July 2018

Mapping genotype to phenotype is challenging because of the difficulties in identifying both the traits under selection and the specific genetic variants underlying these traits. Most of the current knowledge of the genetic basis of adaptive evolution is based on the analysis of single nucleotide polymorphisms (SNPs). Despite increasing evidence for their causal role, the contribution of structural variants to adaptive evolution remains largely unexplored. In this work, we analyzed the population frequencies of 1,615 Transposable Element (TE) insertions in 91 samples from 60 worldwide natural populations ofDrosophila melanogaster. We identified a set of 300 TEs that are present at high population frequencies, and located in genomic regions with high recombination rate, where the efficiency of natural selection is high. The age and the length of these 300 TEs are consistent with relatively young and long insertions reaching high frequencies due to the action of positive selection. Indeed, we, and others, found evidence of selective sweeps and/or population differentiation for 65 of them. The analysis of the genes located nearby these 65 candidate adaptive insertions suggested that the functional response to selection is related with the GO categories of response to stimulus, behavior, and development. We further showed that a subset of the candidate adaptive TEs affect expression of nearby genes, and five of them have already been linked to an ecologically relevant phenotypic effect. Our results provide a more complete understanding of the genetic variation and the fitness-related traits relevant for adaptive evolution. Similar studies should help uncover the importance of TE-induced adaptive mutations in other species as well.
The structural extraction of Chinese medical narratives
Authors: Zhang Rongzhi , Zhang Haifei , Yao Zhiyu , Huang Zhengxing
Published: July 2018

Medical narratives document a vast amount of clinical data. This data has a valuable secondary purpose, as it may be used to optimize health service delivery and improve the quality of medical care. However, medical narratives are typically recorded in an unstructured manner, which complicates the process of extracting the structured information required for optimization. In this paper, we address this problem by applying and comparing two models, a rule-based model and a model based on conditional random fields (CRFs), to a data set of Chinese medical narratives. Among 4626 manually annotated Chinese medical narratives, collected from Shanxi Dayi Hospital in China, the rule-based model achieved 95.87% precision, 69.82% recall, and an F-score of 80.80%, and the CRF-based model realized 95.99% precision, 65.11% recall, and a 77.59% F-score. These experimental results demonstrate the efficacy of both proposed models for structural extraction from Chinese medical narratives.
SREBP1 drives KRT80-dependent cytoskeletal changes and invasive behavior in endocrine resistant ERα breast cancer
Authors: Perone Ylenia , Farrugia Aaron J. , Meira Alba Rodriguez , Győrffy Balázs , Ion Charlotte , Uggetti Andrea , Patten Darren , Chronopoulos Antonios , Faronato Monica , Shousha Sami , Steel Jenny H , Davies Claire , Patel Naina , Rio Hernandez Armando del , Coombes Charles , Pruneri Giancarlo , Lim Adrian , Calvo Fernando , Magnani Luca
Published: July 2018

Approximately 30% of women diagnosed with ERα breast cancer relapse with metastatic disease following adjuvant treatment with endocrine therapies1,2. The connection between acquisition of drug resistance and invasive potential is poorly understood. In this study, we demonstrate that the type II keratin topological associating domain (TAD)3 undergoes epigenetic reprogramming in cells that develop resistance to aromatase inhibitors (AI), leading to keratin 80 (KRT80) upregulation. In agreement, an increased number of KRT80-positive cells are observed at relapse in vivo while KRT80 expression associates with poor outcome using several clinical endpoints. KRT80 expression is driven by de novo enhancer activation by sterol regulatory element-binding protein 14 (SREBP1). KRT80 upregulation directly promotes cytoskeletal rearrangements at the leading edge, increased focal adhesion maturation and cellular stiffening, which collectively promote cancer cell invasion. Shear-wave elasticity imaging of prospective patients shows that KRT80 levels correlate with stiffer tumors in vivo. Collectively, our data uncover an unpredicted and potentially targetable direct link between epigenetic and cytoskeletal reprogramming promoting cell invasion in response to chronic AI treatment.
On the Depth of Deep Learning Models for Splice Site Identification
Authors: Elsousy Reem , Kathiresan Nagarajan , Boughorbel Sabri
Published: July 2018

The success of deep learning has been shown in various fields including computer vision, speech recognition, natural language processing and bioinformatics. The advance of Deep Learning in Computer Vision has been an important source of inspiration for other research fields. The objective of this work is to adapt known deep learning models borrowed from computer vision such as VGGNet, Resnet and AlexNet for the classification of biological sequences. In particular, we are interested by the task of splice site identification based on raw DNA sequences. We focus on the role of model architecture depth on model training and classification performance.

We show that deep learning models outperform traditional classification methods (SVM, Random Forests, and Logistic Regression) for large training sets of raw DNA sequences. Three model families are analyzed in this work namely VGGNet, AlexNet and ResNet. Three depth levels are defined for each model family. The models are benchmarked using the following metrics: Area Under ROC curve (AUC), Number of model parameters, number of floating operations. Our extensive experimental evaluation show that shallow architectures have an overall better performance than deep models. We introduced a shallow version of ResNet, named S-ResNet. We show that it gives a good trade-off between model complexity and classification performance.

Author summary

Deep Learning has been widely applied to various fields in research and industry. It has been also succesfully applied to genomics and in particular to splice site identification. We are interested in the use of advanced neural networks borrowed from computer vision. We explored well-known models and their usability for the problem of splice site identification from raw sequences. Our extensive experimental analysis shows that shallow models outperform deep models. We introduce a new model called S-ResNet, which gives a good trade-off between computational complexity and classification accuracy.
Comments on `Hydrogen bonds in crystalline D-alanine: diffraction and spectroscopic evidence for differences between enantiomers'
Authors: Bürgi Hans-Beat , Macchi Piero
Published: July 2018

The recent paper by Belo, Pereira, Freire, Argyriou, Eckert & Bordallo [(2018), IUCrJ, 5, 6–12] reports observations that may lead one to think of very strong and visible consequences of the parity-violation energy difference between enantiomers of a molecule, namely alanine. If proved, this claim would have an enormous impact for research in structural chemistry. However, alternative, more realistic, explanations of their experiments have not been ruled out by the authors. Moreover, the theoretical calculations carried out to support the hypothesis are unable to differentiate between enantiomers (molecules or crystals). Therefore, the conclusions drawn by Belo et al. (2018) are deemed inappropriate as the data presented do not contain sufficient information to reach such a conclusion.
Characterizing peer-judged answer quality on academic Q&A sites
Authors: Li Lei , He Daqing , Zhang Chengzhi , Geng Li , Zhang Ke
Published: July 2018

Purpose

Academic social (question and answer) Q&A sites are now utilised by millions of scholars and researchers for seeking and sharing discipline-specific information. However, little is known about the factors that can affect their votes on the quality of an answer, nor how the discipline might influence these factors. The paper aims to discuss this issue.

Design/methodology/approach

Using 1,021 answers collected over three disciplines (library and information services, history of art, and astrophysics) in ResearchGate, statistical analysis is performed to identify the characteristics of high-quality academic answers, and comparisons were made across the three disciplines. In particular, two major categories of characteristics of the answer provider and answer content were extracted and examined.

Findings

The results reveal that high-quality answers on academic social Q&A sites tend to possess two characteristics: first, they are provided by scholars with higher academic reputations (e.g. more followers, etc.); and second, they provide objective information (e.g. longer answer with fewer subjective opinions). However, the impact of these factors varies across disciplines, e.g., objectivity is more favourable in physics than in other disciplines.

Originality/value

The study is envisioned to help academic Q&A sites to select and recommend high-quality answers across different disciplines, especially in a cold-start scenario where the answer has not received enough judgements from peers.
Does the New Rural Pension Scheme crowd out private transfers from children to parents? Empirical evidence from China
Authors: Ning Manxiu , Liu Weiping , Gong Jinquan , Liu Xudong
Published: July 2018

Purpose

The purpose of this paper is to examine the effect of New Rural Pension Scheme (NRPS) on the private transfer behavior of the non-co-resident adult children to their elderly parents in rural China, and hence address the income redistribution effectiveness of public program for the elderly in rural China.

Design/methodology/approach

Pooled data from two waves of the China Health and Retirement Longitudinal Study and the combination of regression discontinuity design and difference in difference method are used to perform the analysis.

Findings

No evidence is found that pension payment from NRPS program does significantly crowd out the economic support from the adult children to their elder parents. The heterogeneous effects at different income percentile indicate that pension payment significantly increases the probability of receiving gross transfers and likelihood of the net transfer being positive for those elderly individuals with low income; in particular, the distinctive “family binding” arrangement may dramatically contribute to increasing the probability of receiving private transfers for the pension recipients.

Originality/value

The empirical findings would have far-reaching implications for the efficacy of public transfer or re-distributive programs such as NRPS; for the rural elderly, in particular, the unique “family binding” mechanism under the NRPS program may have positive welfare effects on the intended beneficiaries. Furthermore, an understanding of the inter-linkage between informal arrangements of elderly support and social re-distributive program provides further insight into the design of social security systems targeted to the vulnerable group in developing countries.
Constructing reading proficiency and struggle through tracked contexts
Authors: Learned Julie E. , Morgan Mary Jo
Published: July 2018

Purpose

This paper aims to report on a study investigating how young people and teachers interpreted reading proficiency and difficulty across different tracks of English language arts in the sole high school serving a culturally diverse city.

Design/methodology/approach

For six months, the researchers observed in three hierarchically tracked English classes. Participants were three teachers and 15 focal youths. The researchers also conducted semi-structured and open-ended interviews and collected classroom artifacts and students’ records.

Findings

Despite adoption of the Common Core State Standards and a school-designed common English curriculum, both of which were to contribute to shared literacy objectives, students and teachers built highly contextualized understandings of reading proficiency, which diverged across tracks and mediated instruction. Across tracks, however, deficit discourses about reading struggle persisted, and students and teachers attributed difficulty to students’ attitudes and behaviors. Young people never described themselves in negative terms, which suggests they resisted the deficit labels tracking systems can generate.

Originality/value

Findings extend research by showing how literacy-related tracking contributed to exclusionary contexts through which students were unproductively positioned at odds. Findings suggest a need for renewed rigor in the examination of tracking practices, particularly how notions of reading difficulty/proficiency position youths and mediate literacy instruction. Despite deficit conceptions of “struggling readers” across the school, youths never described themselves negatively and accepted reading difficulty as normal; how youths achieved such resourceful stances can be further investigated. These research directions will support the creation of English contexts that invite all youths into inquisitive, critical and agentive interactions with texts and each other.
Project risk management practices: the organizational maturity influence
Authors: Crispim José , Silva Luiz Henrique , Rego Nazaré
Published: July 2018

Purpose

The purpose of this paper is to identify patterns of project risk management (PRM) practices’ adoption, and provides empirical evidence concerning the importance (and key attributes) of organizational PRM maturity to the use of risk-related practices and project performance.

Design/methodology/approach

The research involved two phases: interviews with five project managers, and a worldwide survey of project managers that resulted in the analysis of 865 valid questionnaire responses. Cluster analysis was used to classify PRM practices’ use, factor analysis to detect the structure of the relationship between the variables measuring PRM practices’ use and a multiple regression analysis (with canonical correlation) to further reveal the different degrees to which PRM practices and organizational maturity are associated.

Findings

The identified patterns of risk practices’ adoption indicate that different contexts of organization PRM maturity and project complexity influence practices selection. The PRM practices related with targets (e.g. time-phased budget plan) are the most used, and those related to tools and techniques (e.g. S-curve) are the least used. Additionally, the obtained results confirm that organizational PRM maturity influences risk practices’ usage, moderated by project complexity, and organizational PRM maturity influences project performance.

Originality/value

Empirical methods were used to investigate the relationship between organizational PRM maturity and a large set of PRM practices with project complexity as a moderator. Gaps in the use of PRM practices (i.e. areas where more PRM knowledge and training are needed) were identified. Finally, this work identifies the attributes of organizational maturity with implications in practices’ usage and project performance.
Does a more complex service offering increase uncertainty in operations?
Authors: Kreye Melanie E.
Published: July 2018

Purpose

The purpose of this paper is to investigate how the complexity of the service offering (service complexity) affects the uncertainty during service operations in engineering services. Specifically, the authors compare the existence of organisational, relational, environmental and technological uncertainty in maintenance services and performance-based services.

Design/methodology/approach

The authors present insights from four cases – two each for maintenance services and performance-based services. The in-depth data were based on 56 semi-structured interviews, multiple site visits, meeting notes, service contracts and other secondary data.

Findings

The case findings indicate that organisational and relational uncertainty were not linked to service complexity, while observations of environmental and technological uncertainty were higher and more varied for performance-based services. Based on these findings, the authors formulate four propositions regarding the relationship between service complexity and uncertainty in service operations.

Originality/value

This research contributes to the OM literature by suggesting that external sources of uncertainty increase with increasing service complexity, while internal sources of uncertainty remain unchanged.
Horizontal collaboration in response to modern slavery legislation
Authors: Benstead Amy V. , Hendry Linda C. , Stevenson Mark
Published: July 2018

Purpose

The purpose of this paper is to investigate how horizontal collaboration aids organisations in responding to modern slavery legislation and in gaining a socially sustainable competitive advantage.

Design/methodology/approach

Action research has been conducted in the textiles and fashion industry and a relational perspective adopted to interpret five collaborative initiatives taken to tackle modern slavery (e.g. joint training and supplier audits). The primary engagement has been with a multi-billion pound turnover company and its collaborations with 35 brands/retailers. A non-government organisation and a trade body have also participated.

Findings

Successful horizontal collaboration is dependent on both relational capital and effective (formal and informal) governance mechanisms. In collaborating, firms have generated relational rents and reduced costs creating a socially sustainable competitive advantage, as suggested by the relational perspective. Yet, limits to horizontal collaboration also exist.

Research limitations/implications

The focus is on one industry only, hence there is scope to extend the study to other industries or forms of collaboration taking place across industries.

Practical implications

Successful horizontal collaborative relationships rely on actors having a similar mindset and being able to decouple the commercial and sustainability agendas, especially when direct competitors are involved. Further, working with non-business actors can facilitate collaboration and provide knowledge and resources important for overcoming the uncertainty that is manifest when responding to new legislation.

Social implications

Social sustainability improvements aim to enhance ethical trade and benefit vulnerable workers.

Originality/value

Prior literature has focussed on vertical collaboration with few prior studies of horizontal collaboration, particularly in a socially sustainable supply chain context. Moreover, there has been limited research into modern slavery from a supply chain perspective. Both successful and unsuccessful initiatives are studied, providing insights into (in)effective collaboration.
Modeling brand market share change in emerging markets
Authors: Romaniuk Jenni , Dawes John , Nenycz-Thiel Magda
Published: July 2018

Purpose

The purpose of this paper is to examine what happens to key brand performance metrics as brands change in market share, in the context of packaged goods. The metrics are: penetration—the number of buyers a brand has; and loyalty—measured as purchase frequency (PF) and share of category requirements (SCR).

Design/methodology/approach

The study utilizes 24 data sets in 17 packaged goods categories in three emerging markets: China, Malaysia and Indonesia. The authors examine changes in penetration, loyalty and SCR in the context of volume and value market share change. In addition, the authors examine whether initial price point and price movements influence the results.

Findings

The primary finding is that market share change is accompanied by a greater change in penetration than in any other metric. This finding is very consistent across categories and countries. The relative importance of the two loyalty metrics varies by country. SCR was a stronger factor in Indonesia, while PF was stronger in Malaysia. Analysis indicated that pricing strategy (initial price and promotional depth) did not alter the main pattern of results, suggesting the results hold for brands with different price levels and tactics.

Practical implications

Irrespective of circumstance, to grow in value or volume market share, brands should aim to grow in penetration, while the importance of changes in specific loyalty measures depends on market conditions.

Originality/value

This research extends past research on brand growth to the very different economic, geographic and cultural conditions of three crucially important emerging markets. Its main value lies in recommendations on how much to invest in building the size of the customer base vs consumer retention.
Is human capital the sixth factor?
Authors: Maiti Moinak , Balakrishnan A.
Published: July 2018

Purpose

The purpose of this paper is to focus on one of the major emerging Asian economies – India – to examine the role of human capital in asset prices.

Design/methodology/approach

The analysis uses various statistical techniques (e.g. multifactor regression model, 3D graphs, GRS test and residual graphs) to test the role of human capital in asset prices.

Findings

A six-factor model designed for capturing the size, value, profitability, investment and human capital patterns in average portfolio returns performs better than both Fama–French’s (1993) three- and Fama–French’s (2015) five-factor model. The main problem of six-factor model is its failure in capturing the average returns on “microcap with low-value stocks that are highly profitable invests aggressively for asset growth but invests much lesser for human growth” and “microcap with unprofitable stocks whose returns behave like those of low-value firms with conservative investment”. The study finds the investment factor (CMA) of Fama–French’s (2015) five-factor model as the redundant factor for describing the portfolio average returns in the study sample.

Research limitations/implications

The paper argues that human capital also plays a role in predicting returns. This has significant public policy content.

Originality/value

The present study is novel for several reasons: first, it includes six-factor model descriptions; second, no comprehensive asset pricing study is done with human capital in Asian emerging markets, especially in India. Perhaps, this is the first study to examine whether portfolio returns are affected by the human capital in the Indian context. Third, the study period and methodology used are completely different from the previous studies.
Beyond Brexit’s uncertainty: the foreseeable Britain’s innovative stagnation
Authors: Padilla Alcides J. , Garrido Alexander
Published: July 2018

Purpose

The purpose of this paper is to explore the causes that determine the UK’s civilian research and development (R&D) expenditure to forecast its possible evolution in a post-Brexit scenario.

Design/methodology/approach

The authors use the Johansen’s co-integration analysis for time series.

Findings

The authors find a co-integration relationship between R&D and variables such as exports, military expenditure, patents, EU GDP per capita and USA GDP per capita. The authors also observed a stagnation in the foreseen R&D expenditure over the next five years.

Research limitations/implications

The authors warned that the results can only be viewed as a glance into the understanding of the complex elements that undergird the UK’s civilian, scientific and technological policy-making. But the authors see them as an interesting starting point for scrutinizing current shortcomings in policy-making, while providing clues for corrective action that would otherwise lead the UK to a structural crisis in its economic performance.

Originality/value

This study constitutes a first attempt to account for the loss of the UK’s innovative influence all over the world.
Output growth of the Malaysia’s manufacturing sector – do foreign workers matter?
Authors: Awad Atif , Yussof Ishak , Khalid Norlin
Published: July 2018

Purpose

The purpose of this paper is to examine the impact of migrant workers on the output growth of 15 sub-industries of the manufacturing sector in Malaysia during the period 1990–2008. The paper seeks to answer the following critical questions: what is the impact of migrant workers on the output growth of the manufacturing sector, the leading sector of Malaysian economy? It is possible that migrant workers with different skill levels may have different impacts on output growth of such sector?

Design/methodology/approach

The paper employs three econometric techniques: mean group, dynamic fixed effect and the pooled mean group on extended form for Cobb–Douglas production function.

Findings

The overall findings suggest that due to the inflow of low skills of migrant workers, output growth in the manufacturing sectors is likely to witnesses a marginal decline in the long run.

Originality/value

The present study complements previous studies by providing a quantitative assessment of the impact of migrant workers on output growth in the manufacturing sector in Malaysia, which is not attempted in extant literature. More importantly, the analysis considers the probability that migrant workers with different skill levels may have different impacts on the growth of output in the manufacturing sector.