bluuebunny/crossref_metadata_2025 huggingface dataset:
A data-driven approach to optimising the encoding for multi-shell diffusion MRI with application to neonatal imaging
Authors: Tournier J-Donald , Christiaens Daan , Hutter Jana , Price Anthony N. , Cordero-Grande Lucilio , Hughes Emer , Bastiani Matteo , Sotiropoulos Stamatios N. , Smith Stephen M. , Rueckert Daniel , Counsell Serena J. , Edwards A. David , Hajnal Joseph V.
Published: June 2019

Diffusion MRI has the potential to provide important information about the connectivity and microstructure of the human brain during normal and abnormal development, non-invasively and in vivo. Recent developments in MRI hardware and reconstruction methods now permit the acquisition of large amounts of data within relatively short scan times. This makes it possible to acquire more informative multi-shell data, with diffusion-sensitisation applied along many directions over multiple b-value shells. Such schemes are characterised by the number of shells acquired, and the specific b-value and number of directions sampled for each shell. However, there is currently no clear consensus as to how to optimise these parameters. In this work, we propose a means of optimising multi-shell acquisition schemes by estimating the information content of the diffusion MRI signal, and optimising the acquisition parameters for sensitivity to the observed effects, in a manner agnostic to any particular diffusion analysis method that might subsequently be applied to the data. This method was used to design the acquisition scheme for the neonatal diffusion MRI sequence used in the developing Human Connectome Project, which aims to acquire high quality data and make it freely available to the research community. The final protocol selected by the algorithm, and currently in use within the dHCP, consists of b = 0, 400, 1000, 2600 s/mm2 with 20, 64, 88 & 128 DW directions per shell respectively.

Highlights

A data driven method is presented to design multi-shell diffusion MRI acquisition schemes (b-values and no. directions).

This method optimises the multi-shell scheme for maximum sensitivity to the information content in the signal.

When applied in neonates, the data suggest that a b=0 + 3 shell strategy is appropriate
Visual dynamics cues in learning complex physical interactions
Authors: Hasson Christopher J. , Jalili Paneed F.
Published: June 2019

This study investigated the role of visual dynamics cues (VDCs) in learning to interact with a complex physical system. Manual gait training was used as an exemplary case, as it requires therapists to control the non-trivial locomotor dynamics of patients. A virtual analog was developed that allowed naïve subjects to manipulate the leg of a virtual stroke survivor (a virtual patient; VP) walking on a treadmill using a small robotic manipulandum. The task was to make the VP’s leg pass through early, mid, and late swing gait targets. One group of subjects (n = 17) started practice seeing the VP’s affected thigh and shank (i.e., VDCs); a second control group (n = 16) only saw the point-of-contact (VP ankle). It was hypothesized that, if seeing the VP’s leg provides beneficial dynamics information, the VDC group would have better task performance and generalization than controls. Results were not supportive. Both groups had similar task performance, and for the late swing gait target, a decrement in manipulative accuracy was observed when VDCs were removed in a generalization task. This suggests that when learning to manipulate complex dynamics, VDCs can create a dependency that negatively affects generalization if the visual context is changed.
Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth
Authors: Everson Todd M. , Vives-Usano Marta , Seyve Emie , Cardenas Andres , Lacasaña Marina , Craig Jeffrey M. , Lesseur Corina , Baker Emily R. , Fernandez-Jimenez Nora , Heude Barbara , Perron Patrice , Gónzalez-Alzaga Beatriz , Halliday Jane , Deyssenroth Maya A. , Karagas Margaret R. , Íñiguez Carmen , Bouchard Luigi , Carmona-Sáez Pedro , Loke Yuk J. , Hao Ke , Belmonte Thalia , Charles Marie A. , Martorell-Marugán Jordi , Muggli Evelyne , Chen Jia , Fernández Mariana F. , Tost Jorg , Gómez-Martín Antonio , London Stephanie J. , Sunyer Jordi , Marsit Carmen J. , Lepeule Johanna , Hivert Marie-France , Bustamante Mariona
Published: June 2019

Maternal smoking during pregnancy (MSDP) contributes to poor birth outcomes, in part through disrupted placental functions, which may be reflected in the placental epigenome. We meta-analyzed the associations between MSDP and placental DNA methylation (DNAm) and between DNAm and birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (7 studies, N=1700, 344 with any MSDP). We identified 1224 CpGs that were associated with MSDP, of which 341 associated with birth outcomes and 141 associated with gene expression. Only 6 of these CpGs were consistent with the findings from a prior meta-analysis of cord blood DNAm, demonstrating substantial tissue-specific responses to MSDP. The placental MSDP associated CpGs were enriched for growth-factor signaling, hormone activity, inflammation, and vascularization, which play important roles in placental function. We demonstrate links between placental DNAm, MSDP and poor birth outcomes, which may better inform the mechanisms through which MSDP impacts placental function and fetal growth.
Defining the Energetic Costs of Cellular Structures
Authors: Mahmoudabadi Gita , Phillips Rob , Lynch Michael , Milo Ron
Published: June 2019

All cellular structures are assembled from molecular building blocks, and molecular building blocks incur energetic costs to the cell. In an energy-limited environment, the energetic cost of a cellular structure imposes a fitness cost and impacts a cell’s evolutionary trajectory. While the importance of energetic considerations was realized for decades, the distinction between direct energetic costs expended by the cell and potential energy that the cell diverts into cellular biomass components, which we define as the opportunity cost, was not explicitly made, leading to large differences in values for energetic costs of molecular building blocks used in the literature. We describe a framework that defines and separates various components relevant for estimating the energetic costs of molecular building blocks and the resulting cellular structures. This distinction among energetic costs is an essential step towards discussing the conversion of an energetic cost to a corresponding fitness cost.
Integrated Identification of Disease Specific Pathways Using Multi-omics data
Authors: Lu Yingzhou , Chang Yi-Tan , Hoffman Eric P. , Yu Guoqiang , Herrington David M. , Clarke Robert , Wu Chiung-Ting , Chen Lulu , Wang Yue
Published: June 2019

Motivation

Identification of biological pathways plays a central role in understanding both human health and diseases. Although much work has previously been done to explore the biological pathways by using single omics data, little effort has been reported using multi-omics data integration, mainly due to methodological and technological limitations. Compared to single omics data, multi-omics data will help identifying disease specific functional pathways with both higher sensitivity and specificity, thus gaining more comprehensive insights into the molecular architecture of disease processes.

Results

In this paper, we propose two computational approaches that integrate multi-omics data and identify disease-specific biological pathways with high sensitivity and specificity. Applying our methods to an experimental multi-omics data dataset on muscular dystrophy subtypes, we identified disease-specific pathways of high biological plausibility. The developed methodology will likely have a broad impact on improving the molecular characterization of many common diseases.

Contact

yuewang@vt.edu

Supplementary information

Supplementary information attached.
Serological and metagenomic interrogation of cerebrospinal fluid implicates enteroviruses in pediatric acute flaccid myelitis
Authors: Schubert Ryan D. , Hawes Isobel , Ramachandran Prashanth S. , Ramesh Akshaya , Crawford Emily D. , Pak John E. , Wu Wesley , Cheung Carly K. , O’Donovan Brian D. , Tato Cristina M. , Lyden Amy , Tan Michelle , Sit Rene , Sowa Gavin , Sample Hannah A. , Zorn Kelsey C. , Banerji Debarko , Khan Lillian M. , Bove Riley , Hauser Stephen L. , Gelfand Amy A. , Johnson-Kerner Bethany , Nash Kendall , Krishnamoorthy Kalpathy S. , Chitnis Tanuja , Ding Joy Z. , McMillan Hugh J. , Chiu Charles Y. , Briggs Benjamin , Glaser Carol A. , Yen Cynthia , Chu Victoria , Wadford Debra A. , Dominguez Samuel R. , Ng Terry Fei Fan , Marine Rachel L. , Lopez Adriana S. , Nix W. Allan , Soldatos Ariane , Gorman Mark P. , Benson Leslie , Messacar Kevin , Konopka-Anstadt Jennifer L. , Oberste M. Steven , DeRisi Joseph L. , Wilson Michael R.
Published: June 2019

Background

Since 2014, the United States has experienced a biennial spike in pediatric acute flaccid myelitis (AFM). Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF) and only inconsistently identified from the respiratory tract, serum, or stool.

Methods

We interrogated CSF from children with AFM (n=42) and pediatric controls with other neurologic diseases (OND) (n=58). Samples were incubated with T7 bacteriophage expressing 481,966 sixty-two amino acid peptides with a fourteen amino acid overlap tiled across all known vertebrate virus and arbovirus genomes, an adaption of the VirScan method. Antibody-bound phage were deep sequenced to quantify enriched peptides with normalized counts expressed as reads per hundred thousand (rpK). EV antibody findings were confirmed with ELISA using whole viral protein 1 (VP1) from contemporary enterovirus (EV) A71 and D68 strains. Separately, metagenomic next-generation sequencing (mNGS) of CSF RNA, both unbiased and with targeted enrichment for EVs, was performed.

Results

The most significantly enriched viral family by VirScan of CSF in AFM versus OND controls wasPicornaviridae(mean rpK 11,266 versus mean rpK 950, p-adjusted < 0.001, Wilcoxon signed-rank test with Bonferroni adjustment). EnrichedPicornaviridaepeptides belonged almost entirely to the genusEnterovirus.The mean EV VP1 ELISA signal in AFM (mean OD 0.51) was significantly higher than OND controls (mean OD 0.08, p-value < 0.001, Mann-Whitney test). mNGS did not detect additional enterovirus RNA in CSF.

Conclusion

Despite the rare detection of EV RNA in the CNS of patients with AFM, a pan-viral serologic assay identified high levels of CSF EV antibodies in AFM CSF compared to CSF from OND controls. These results provide further evidence for a causal role of non-polio enteroviruses in AFM.
Distinct gut metagenomics and metaproteomics signatures in prediabetics and treatment-naïve type 2 diabetics
Authors: Zhong Huanzi , Ren Huahui , Lu Yan , Fang Chao , Hou Guixue , Yang Ziyi , Chen Bing , Yang Fangming , Zhao Yue , Shi Zhun , Zhou Baojin , Wu Jiegen , Zou Hua , Zi Jin , Chen Jiayu , Bao Xiao , Hu Yihe , Gao Yan , Zhang Jun , Xu Xun , Hou Yong , Yang Huanming , Wang Jian , Liu Siqi , Jia Huijue , Madsen Lise , Brix Susanne , Liu Fang , Kristiansen Karsten , Li Junhua
Published: June 2019

Background

The gut microbiota plays important roles in modulating host metabolism. Previous studies have demonstrated differences in the gut microbiome of T2D and prediabetic individuals compared to healthy individuals, with distinct disease-related microbial profiles being reported in groups of different age and ethnicity. However, confounding factors such as anti-diabetic medication hamper identification of the gut microbial changes in disease development.

Method

We used a combination of in-depth metagenomics and metaproteomics analyses of faecal samples from treatment-naïve type 2 diabetic (TN-T2D, n=77), pre-diabetic (Pre-DM, n=80), and normal glucose tolerant (NGT, n=97) individuals to investigate compositional and functional changes of the gut microbiota and the faecal content of microbial and host proteins in Pre-DM and treatment-naïve T2D individuals to elucidate possible host-microbial interplays characterising different disease stages.

Findings

We observed distinct differences characterizing the gut microbiota of these three groups and validated several key features in an independent TN-T2D cohort. We also demonstrated that the content of several human antimicrobial peptides and pancreatic enzymes differed in faecal samples between three groups, such as reduced faecal level of antimicrobial peptides and pancreatic enzymes in TN-T2D.

Interpretation

Our findings suggest a complex, disease stage-dependent interplay between the gut microbiota and the host and emphasize the value of metaproteomics to gain further insight into interplays between the gut microbiota and the host.

Funding

National Key Research and Development Program of China, No. 2017YFC0909703, Shenzhen Municipal Government of China, No. JCYJ20170817145809215, and National Natural Science Foundation of China, No. 31601073.
Next generation taxonomy: integrating traditional species description with the holobiont concept and genomic approaches - The in-depth characterization of a novelEuplotesspecies as a case study
Authors: Serra Valentina , Gammuto Leandro , Nitla Venkatamahesh , Castelli Michele , Lanzoni Olivia , Sassera Davide , Bandi Claudio , Sandeep Bhagavatula Venkata , Verni Franco , Modeo Letizia , Petroni Giulio
Published: June 2019

In 1991 Margulis defined holobionts as the assemblage of “two or more organisms, members of different species” which remain associate “throughout a significant portion of the life history”. In recent times, holobionts have been described among many and far-related groups of living beings, such as plants, algae, insects, corals, and even humans. These studies have arisen an increasing interest in different contexts but, to our knowledge, the holobiont concept has not been applied in taxonomy. Here we propose a new approach to modern taxonomy, aimed to integrate the holobiont concept and genomic and bioinformatic analyses with the classical/morphological tools traditionally used in taxonomy. The inclusion of symbiont morphology, and of mitochondrial and symbiont genomes will allow the discipline to move toward what could become the “next generation taxonomy”. As an example of this new paradigm in the characterization of holobionts, we herein provide the taxonomic description of the ciliate protistEuplotes vanleeuwenhoekisp. nov. (Euplotia, Ciliophora) and its bacterial endosymbiont “CandidatusPinguicoccus supinus” gen. nov., sp. nov. (Opitutae, Verrucomicrobia). Interestingly, we found that this endosymbiont has an extremely reduced genome (~163 Kbp), which is suggestive of a high integration with the host and represents the first case of such an extreme reduction inVerrucomicrobia, and the first case in a protist host.
miR-467 regulates inflammation and blood insulin and glucose
Authors: Gajeton Jasmine , Krukovets Irene , Yendamuri Revanth , Verbovetskiy Dmitriy , Vasanji Amit , Sul Lidiya , Stenina-Adognravi Olga
Published: June 2019

Obesity is associated with inflammation and insulin resistance (IR), but the regulation of insulin sensitivity (IS) and connections between IS and inflammation remain unclear. We investigated the role of miR-467a-5p, a miRNA induced by hyperglycemia, in regulating inflammation and blood glucose handling.

We previously demonstrated that miR-467a-5p is induced by hyperglycemia and inhibits the production of thrombospondin-1 (TSP-1), a protein implicated in regulating inflammation. To investigate the role of miR-467 in blood glucose handling and tissue inflammation, WT C57/BL6 mice were fed chow or Western diet from 5 to 32 weeks of age and injected weekly with miR-467a-5p antagonist. Inhibiting miR-467a-5p resulted in 47% increase in macrophage infiltration and increased Il6 levels in adipose tissue, higher plasma insulin levels (98 vs 63 ng/mL), and 17% decrease in glucose clearance without increase in weight or HDL/LDL. The antagonist effect was lost in mice on Western diet. Mice lacking TSP-1 lost some but not all of the miR-467 effects, suggesting Thbs1−/− (and other unknown transcripts) are targeted by miR-467 to regulate inflammation.

miR-467a-5p provides a physiological feedback when blood glucose is elevated to avoid inflammation and increased blood glucose and insulin levels, which may prevent IR.
Rab11b-mediated integrin recycling promotes brain metastatic adaptation and outgrowth
Authors: Howe Erin N. , Burnette Miranda D. , Justice Melanie E. , Clancy James W. , Guldner Ian H. , Schnepp Patricia M. , Hendrick Victoria , Aryal Uma K. , Specht Alicia T. , Li Jun , D’Souza-Schorey Crislyn , Zartman Jeremiah Z. , Zhang Siyuan
Published: June 2019

GRAPHICAL ABSTRACT

Breast cancer brain metastases (BCBM) have a 5-20 year latency and account for up to 30% of mortality. Developing new therapeutics requires a molecular understanding of adaptation to the brain microenvironment. Here, we combined RNA-sequencing of BCBM development with a reverse genetic screen in Drosophila melanogaster and identified Rab11b, an endosomal recycling protein, as a mediator of metastatic adaptation. We show that disseminated cells up-regulate Rab11b early after arrival in the brain, allowing control of the cell surface proteome through recycling of proteins required for successful interaction with the microenvironment, including integrin β1. Rab11b-mediated control of integrin β1 surface expression allows ligation to the brain ECM, activating mechanotransduction signaling to allow survival and proliferation. We propose a model in which up-regulation of Rab11b allows disseminated cells to recycle needed proteins during metastatic adaptation, without strictly requiring transcription and translation, to allow for metastatic outgrowth.

Manuscript Summary

Rab11b up-regulation in the brain microenvironment promotes recycling of cargo proteins required for breast cancer brain metastasis, including increased surface expression of integrin β1, which allows brain extracellular matrix attachment and mechanotransduction. Inhibition of the mevalonate pathway with statins prevents geranylgeranylation of Rab11b, decreasing cargo recycling, and inhibiting brain metastasis.
Integrative analysis reveals RNA G-Quadruplexes in UTRs are selectively constrained and enriched for functional associations
Authors: Lee David S.M. , Ghanem Louis R. , Barash Yoseph
Published: June 2019

Identifying regulatory elements in the noncoding genome is a fundamental challenge in biology. G-quadruplex (G4) sequences are abundant in untranslated regions (UTRs) of human messenger RNAs, but their functional importance remains unclear. By integrating multiple sources of genetic and genomic data, we show that putative G-quadruplex forming sequences (pG4) in 5’ and 3’ UTRs are selectively constrained, and enriched for cis-eQTLs and RNA-binding protein (RBP) interactions. Using over 15,000 whole-genome sequences, we uncover a degree of negative (purifying) selection in UTR pG4s comparable to that of missense variation in protein-coding sequences. In parallel, we identify new proteins with evidence for preferential binding at pG4s from ENCODE annotations, and delineate putative regulatory networks composed of shared binding targets. Finally, by mapping variants in the NIH GWAS Catalogue and ClinVar, we find enrichment for disease-associated variation in 3’UTR pG4s. At a GWAS pG4-variant associated with hypertension in HSPB7, we uncover robust allelic imbalance in GTEx RNA-seq across multiple tissues, suggesting that changes in gene expression associated with pG4 disruption underlie the observed phenotypic association. Taken together, our results establish UTR G-quadruplexes as important cis-regulatory features, and point to a putative link between disruption within UTR pG4 and susceptibility to human disease.
Cancer Exacerbates Chemotherapy Induced Sensory Neuropathy
Authors: Housley Stephen N. , Nardelli Paul , Carrasco Dario , Pfahl Emily , Matyunina Lilya , McDonald John F. , Cope Timothy C.
Published: June 2019

For the constellation of neurological disorders known as chemotherapy induced peripheral neuropathy, mechanistic understanding, and treatment remain deficient. Here we present the first evidence in preclinical investigation of rats that chronic sensory neuropathy depends on non-linear interactions between cancer and chemotherapy. Global transcriptional profiling of dorsal root ganglia revealed differential expression, notably in regulators of neuronal excitability, metabolism and inflammatory responses, all of which were unpredictable from effects observed with either chemotherapy or cancer alone. Systemic interactions between cancer and chemotherapy also determined the extent of deficits in sensory encoding and ion channel protein expression by single mechanosensory neurons, with the potassium ion channel Kv3.3 emerging as a potential contributor to sensory neuron dysfunction. These original findings identify novel contributors to peripheral neuropathy, and emphasize the fundamental dependence of neuropathy on the systemic interaction between chemotherapy and cancer.
NEURAL POPULATION DYNAMICS IN MOTOR CORTEX ARE DIFFERENT FOR REACH AND GRASP
Authors: Suresh Aneesha K. , Goodman James M. , Okorokova Elizaveta V. , Kaufman Matthew T. , Hatsopoulos Nicholas G. , Bensmaia Sliman J.
Published: June 2019

Abstract

Rotational dynamics are observed in neuronal population activity in primary motor cortex (M1) when monkeys make reaching movements. This population-level behavior is consistent with a role for M1 as an autonomous pattern generator that drives muscles to produce movement. Here, we show that M1 does not exhibit smooth dynamics during grasping movements, suggesting a more input-driven circuit.
Robust Cancer Mutation Detection with Deep Learning Models Derived from Tumor-Normal Sequencing Data
Authors: Sahraeian Sayed Mohammad Ebrahim , Fang Li Tai , Mohiyuddin Marghoob , Hong Huixiao , Xiao Wenming
Published: June 2019

Accurate detection of somatic mutations is challenging but critical to the understanding of cancer formation, progression, and treatment. We recently proposed NeuSomatic, the first deep convolutional neural network based somatic mutation detection approach and demonstrated performance advantages on in silico data. In this study, we used the first comprehensive and well-characterized somatic reference samples from the SEQC-II consortium to investigate best practices for utilizing deep learning framework in cancer mutation detection. Using the high-confidence somatic mutations established for these reference samples by the consortium, we identified strategies for building robust models on multiple datasets derived from samples representing real scenarios. The proposed strategies achieved high robustness across multiple sequencing technologies such as WGS, WES, AmpliSeq target sequencing for fresh and FFPE DNA input, varying tumor/normal purities, and different coverages (ranging from 10× - 2000×). NeuSomatic significantly outperformed conventional detection approaches in general, as well as in challenging situations such as low coverage, low mutation frequency, DNA damage, and difficult genomic regions.
Multi-scale dynamical modelling of T-cell development from an early thymic progenitor state to lineage commitment
Authors: Olariu Victor , Yui Mary A. , Krupinski Pawel , Zhou Wen , Deichmann Julia , Rothenberg Ellen V. , Peterson Carsten
Published: June 2019

Thymic development of committed pro-T-cells from multipotent hematopoietic precursors offers a unique opportunity to dissect the molecular circuitry establishing cell identity in response to environmental signals. This transition encompasses programmed shutoff of stem/progenitor genes, upregulation of T-cell specification genes, extensive proliferation, and commitment after a delay. We have incorporated these factors, as well as new single cell gene expression and developmental kinetics data, into a three-level dynamic model of commitment based upon regulation of the commitment geneBcl11b. The first level is a core gene regulatory network architecture determined by transcription factor perturbation data, the second a stochastically controlled epigenetic gate, and the third a proliferation model validated by growth and commitment kinetics measured at single-cell levels. Using expression values consistent with single molecule RNA-FISH measurements of key transcription factors, this single-cell model exhibits state switching consistent with measured population and clonal proliferation and commitment times. The resulting multi-scale model provides a powerful mechanistic framework for dissecting commitment dynamics.
Intracerebral transfection of anti-rabies virus antibodies is an effective therapy for rabies
Authors: Agostinho Washington C. , Brandão Paulo E.
Published: June 2019

Rabies is a zoonotic neurological disease with 100% lethality. Some of the rare human patients who survived after multiple drug treatment have inherited severe sequelae. The objective of this study was to investigate the action of the transfection of antibodies against rabies in the central nervous system of mice as target therapy for rabies.

Author summary

The present study showed that after 48 h of RABV inoculation, mice injected by the intracerebral route with anti-RABV F(ab’)2 complexed with Bioporter® Protein Delivery Reagent (Genlantis) as a transfection agent, showing a morbidity/mortality rate of 30% with a minimum incubation period of seven days, while in the control group a significantly higher (p<0.0198) 90% morbidity/mortality was reached in thirteen days after a maximum 5-day incubation period, suggesting that the transfection of anti-RABV antibodies into the brain might prevent or delay RABV dissemination in an early stage of rabies infection. For the first time, a single compound was able to inhibit replication of the virus in the nervous system with high efficiency. This result can provide important results for the planning of protocols to prevent the fatal outcome of the disease in advanced stages. New studies focusing on the optimization of intracellular antibody delivery may be one of the main bases for more effective anti-rabies therapy.
Histone methyltransferase PRDM9 is not essential for meiosis in male mice
Authors: Mihola Ondrej , Pratto Florencia , Brick Kevin , Linhartova Eliska , Kobets Tatyana , Flachs Petr , Baker Christopher L. , Sedlacek Radislav , Paigen Kenneth , Petkov Petko M. , Camerini-Otero R. Daniel , Trachtulec Zdenek
Published: June 2019

A hallmark of meiosis is the rearrangement of parental alleles to ensure genetic diversity in the gametes. These chromosome rearrangements are mediated by the repair of programmed DNA double-strand breaks (DSBs) as genetic crossovers between parental homologs. In mice, humans, and many other mammals, meiotic DSBs occur primarily at hotspots, determined by sequence-specific binding of the PRDM9 protein. Without PRDM9, meiotic DSBs occur near gene promoters and other functional sites. Studies in a limited number of mouse strains showed that functional PRDM9 is required to complete meiosis, but despite its apparent importance, Prdm9 has been repeatedly lost across many animal lineages. Both the reason for mouse sterility in the absence of PRDM9 and the mechanism by which Prdm9 can be lost remain unclear. Here, we explore whether mice can tolerate the loss of Prdm9. By generating Prdm9 functional knockouts in an array of genetic backgrounds, we observe a wide range of fertility phenotypes and ultimately demonstrate that PRDM9 is not required for completion of male meiosis. Although DSBs still form at a common subset of functional sites in all mice lacking PRDM9, meiotic outcomes differ substantially. We speculate that DSBs at functional sites are difficult to repair as a crossover and that by increasing the efficiency of crossover formation at these sites, genetic modifiers of recombination rates can allow for meiotic progression. This model implies that species with a sufficiently high recombination rate may lose Prdm9 yet remain fertile.
A new in-line X-ray phase-contrast computed tomography reconstruction algorithm based on adaptive-weighted anisotropic TpV regularization for insufficient data
Authors: Zhao Yuqing , Ji Dongjiang , Chen Yingpin , Jian Jianbo , Zhao Xinyan , Zhao Qi , Lv Wenjuan , Xin Xiaohong , Yang Tingting , Hu Chunhong
Published: June 2019

In-line X-ray phase-contrast computed tomography (IL-PCCT) is a valuable tool for revealing the internal detailed structures in weakly absorbing objects (e.g. biological soft tissues), and has a great potential to become clinically applicable. However, the long scanning time for IL-PCCT will result in a high radiation dose to biological samples, and thus impede the wider use of IL-PCCT in clinical and biomedical imaging. To alleviate this problem, a new iterative CT reconstruction algorithm is presented that aims to decrease the radiation dose by reducing the projection views, while maintaining the high quality of reconstructed images. The proposed algorithm combines the adaptive-weighted anisotropic total p-variation (AwaTpV, 0 < p < 1) regularization technique with projection onto convex sets (POCS) strategy. Noteworthy, the AwaTpV regularization term not only contains the horizontal and vertical image gradients but also adds the diagonal image gradients in order to enforce the directional continuity in the gradient domain. To evaluate the effectiveness and ability of the proposed algorithm, experiments with a numerical phantom and synchrotron IL-PCCT were performed, respectively. The results demonstrated that the proposed algorithm had the ability to significantly reduce the artefacts caused by insufficient data and effectively preserved the edge details under noise-free and noisy conditions, and thus could be used as an effective approach to decrease the radiation dose for IL-PCCT.
A simple and compact scheme to enhance the brightness of self-amplified spontaneous emission free-electron-lasers
Authors: Prat Eduard , Reiche Sven
Published: June 2019

A simple and compact scheme that enhances the brightness of self-amplified spontaneous-emission (SASE) free-electron lasers is presented. The method combines the high-brightness SASE scheme and the optical klystron concept to increase the temporal coherence of the produced radiation and to reduce the required length of the undulator beamline at the same time. The scheme is very simple and only requires compact chicanes between the modules of the undulator beamline. Simulations show that, in comparison with SASE, the brightness can be improved by up to a factor of ten and the required length to achieve saturation can be reduced by 20% or more.
Nickel(II) cluster-based mixed-cation coordination polymer synthesized from 2-mercaptobenzoic acid and its application
Authors: Zhu Jingyan , Yan Shan , Xiao Hongping , Jiang Jun , Li Xinhua
Published: June 2019

High-nuclearity metal clusters have received considerable attention not only because of their diverse architectures and topologies, but also because of their potential applications as functional materials in many fields. To explore new types of clusters and their potential applications, a new nickel(II) cluster-based mixed-cation coordination polymer, namely poly[hexakis[μ4-(2-carboxylatophenyl)sulfanido]di-μ3-chlorido-tri-μ2-hydroxido-octanickel(II)sodium(I)], [Ni8NaCl2(OH)3(C7H4O2S)6]
n
, 1, was synthesized using nickel chloride hexahydrate and mercaptobenzoic acid (H2mba) as starting reactants under hydrothermal conditions. The material was characterized by single-crystal X-ray diffraction (SCXRD), Fourier transform IR spectroscopy, thermogravimetric analysis, powder X-ray diffraction and X-ray photoelectron spectroscopy analysis. SCXRD shows that 1 consists of a hexanuclear nickel(II) [Ni6] cluster, dinuclear NiII nodes and a mononuclear NaI node, resulting in the formation of a complex covalent three-dimensional network. In addition, a tightly packed NiO/C&S nanocomposite is fabricated by sintering the coordination precursor at 400 °C. The uniform nanocomposite consists of NiO nanoparticles, incompletely carbonized carbon and incompletely vulcanized sulfur. When used as a supercapacitor electrode, the synthesized composite shows an extra-long cycling stability (>5000 cycles) during the charge/discharge process.
Crystal structure of pirfenidone (5-methyl-1-phenyl-1H-pyridin-2-one): an active pharmaceutical ingredient (API)
Authors: Barbero Mauro , Mossotti Matteo , Sironi Angelo , Giovenzana Giovanni Battista , Colombo Valentina
Published: June 2019

The crystal structure of pirfenidone, C12H11NO [alternative name: 5-methyl-1-phenylpyridin-2(1H)-one], an active pharmaceutical ingredient (API) approved in Europe and Japan for the treatment of Idiopathic pulmonary fibrosis (IPF), is reported here for the first time. It was crystallized from toluene by the temperature gradient technique, and crystallizes in the chiral monoclinic space groupP21. The phenyl and pyridone rings are inclined to each other by 50.30 (11)°. In the crystal, molecules are linked by C–H...O hydrogen bonds involving the same acceptor atom, forming undulating layers lying parallel to theabplane.
Crystal structure and electrical resistance property of Rb0.21(H2O)
y
WS2
Authors: Mao Yuanlv , Fang Yuqiang , Wang Dong , Bu Kejun , Wang Sishun , Zhao Wei , Huang Fuqiang
Published: June 2019

Rb0.21(H2O)
y
WS2, rubidium hydrate dithiotungstate, is a new quasi two-dimensional sulfide. Its crystal structure consists of ordered WS2 layers, separated by disordered Rb+ ions and water molecules. All atomic sites are located on mirror planes. The WS2 layers are composed of edge-sharing [WS6] octahedra and extend parallel to (001). The presence of structural water was revealed by thermogravimetry, but the position and exact amount could not be determined in the present study. The temperature dependence of the electrical resistance indicates that Rb0.21(H2O)
y
WS2 is semiconducting between 80–300 K.
Crystal structure and DFT study of benzyl 1-benzyl-2-oxo-1,2-dihydroquinoline-4-carboxylate
Authors: Bouzian Younos , Faizi Md. Serajul Haque , Mague Joel T. , Otmani Bouchaib El , Dege Necmi , Karrouchi Khalid , Essassi El Mokhtar
Published: June 2019

In the title quinoline derivative, C24H19NO3, the two benzyl rings are inclined to the quinoline ring mean plane by 74.09 (8) and 89.43 (7)°, and to each other by 63.97 (10)°. The carboxylate group is twisted from the quinoline ring mean plane by 32.2 (2)°. There is a short intramolecular C—H...O contact forming an S(6) ring motif. In the crystal, molecules are linked by bifurcated C—H,H...O hydrogen bonds, forming layers parallel to the ac plane. The layers are linked by C—H...π interactions, forming a supramolecular three-dimensional structure.
Industry 4.0 − challenges to implement circular economy
Authors: Rajput Shubhangini , Singh Surya Prakash
Published: June 2019

Purpose

The purpose of this paper is to identify the Industry 4.0 barriers to achieve circular economy (CE). The study focuses on exploring the link between Industry 4.0 and CE. This leads to the implementation of integrated Industry 4.0-CE and attainment of sustainable production and consumption through analyzing the technological benefits of Industry 4.0.

Design/methodology/approach

Industry 4.0 barriers are identified from literature review and discussions with industry experts. Here, the interpretive structural modeling (ISM) technique is applied to develop the contextual relationship among the barriers and to identify the prominent barriers hindering the CE implementation.

Findings

The ISM hierarchical model and Matriced’ impacts croised-multiplication applique’ and classment analysis illustrate that the digitalization process and the semantic interoperability possess high driving power and low dependence. These barriers require keen attention to play a significant role in improving resource efficiency and sustainability, and absence of these barriers may not drive other barriers for CE. Apart from these barriers, cyber-physical systems standards and specifications, sensor technology and design challenges are also the most influential Industry 4.0 barriers for achieving CE.

Practical implications

The findings provide an opportunity for industry practitioners to explore the most driving Industry 4.0 barriers. The study confirms that integrated Industry 4.0-CE will maintain sustainable operations management by optimizing the production and consumption patterns. It will also provide an opportunity of customization where customers and products interact and can monitor the performance of the operations through the Internet of Things sensors.

Originality/value

The study provides integration of Industry 4.0 challenges to implement CE. However, the integration of the two burgeoning fields is still very scarce and lacks in adopting the technological benefits of the integrated Industry 4.0-CE.
Modeling supplier selection in the era of Industry 4.0
Authors: Sachdeva Nitin , Shrivastava Avinash K. , Chauhan Ankur
Published: June 2019

Purpose

The problem of evaluating potential suppliers has always been based on finding an optimal tradeoff between supplier’s performance consistently meeting firms’ needs and acceptable cost. The purpose of this paper is to propose a hybrid multi-criteria decision framework to quantify this qualitative judgment and reduce ambiguity in selection of suppliers in the era of Industry 4.0.

Design/methodology/approach

A hybrid intuitionistic fuzzy entropy weight-based multi-criteria decision model with TOPSIS is proposed. The authors make use of the intuitionistic fuzzy weighted approach operator for aggregating individual decision maker’s opinions regarding each alternative over every criterion. Additionally, the authors employ the concept of Shannon’s entropy to calculate the criteria weights.

Findings

Results obtained on the basis of the proposed hybrid methodology are analyzed against two more cases wherein the authors try to showcase the relevance of using IFS and entropy-based decision framework and find out the uniqueness of the proposed framework in supplier selection process.

Practical implications

The proposed model is apposite to solve management problem of supplier selection in two ways: aggregating individual decision maker’s opinion for each of the predefined criteria along with individual decision maker’s importance and ranking the suppliers based on both positive and negative ideal solutions using TOPSIS.

Originality/value

A robust framework incorporates not only suppliers’ performance but also provides weightage to key decision makers. Especially in the context of MCDMs wherein both qualitative and quantitative data is evaluated simultaneously, the proposed framework is unique in its practical implementation of reducing ambiguity in the supplier selection process.
Improving the bending response of four-node quadrilateral and eight-node hexahedral elements for Cosserat elasticity problems
Authors: Xie Qing , Hu Yucai , Zhou Yexin , Han Wanshui
Published: June 2019

Purpose

Poor bending response is a major shortcoming of lower-order elements due to excessive representation of shear stress/strain field. Advanced finite element (FE) formulations for classical elasticity enhance the bending response by either nullifying or filtering some of the symmetric shear stress/strain modes. Nevertheless, the stress/strain field in Cosserat elasticity is asymmetric; consequently any attempt to nullify or filter the anti-symmetric shear stress/strain modes may lead to failure in the constant couple-stress patch test where the anti-symmetric shear stress/strain field is linear. This paper aims at enhancing the bending response of lower-order elements for Cosserat elasticity problems.

Design/methodology/approach

A four-node quadrilateral and an eight-node hexahedron are formulated by hybrid-stress approach. The symmetric stress is assumed as those of Pian and Sumihara and Pian and Tong. The anti-symmetric stress components are first assumed to be completely linear in order to pass the constant couple-stress patch test. The linear modes are then constrained with respect to the prescribed body-couple via the equilibrium conditions.

Findings

Numerical tests show that the hybrid elements can strictly pass the constant couple-stress patch test and are markedly more accurate than the conventional elements as well as the incompatible elements for bending problems in Cosserat elasticity.

Originality/value

This paper proposes a hybrid FE formulation to improve the bending response of four-node quadrilateral and eight-node hexahedral elements for Cosserat elasticity problems without compromising the constant couple-stress patch test.
Understanding passwords – a taxonomy of password creation strategies
Authors: Kävrestad Joakim , Eriksson Fredrik , Nohlberg Marcus
Published: June 2019

Purpose

Using authentication to secure data and accounts has grown to be a natural part of computing. Even if several authentication methods are in existence, using passwords remains the most common type of authentication. As long and complex passwords are encouraged by research studies and practitioners alike, computer users design passwords using strategies that enable them to remember their passwords. This paper aims to present a taxonomy of those password creation strategies in the form of a model describing various strategies used to create passwords.

Design/methodology/approach

The study was conducted in a three-step process beginning with a short survey among forensic experts within the Swedish police. The model was then developed by a series of iterative semi-structured interviews with forensic experts. In the third and final step, the model was validated on 5,000 passwords gathered from 50 different password databases that have leaked to the internet.

Findings

The result of this study is a taxonomy of password creation strategies presented as a model that describes the strategies as properties that a password can hold. Any given password can be classified as holding one or more of the properties outlined in the model.

Originality/value

On an abstract level, this study provides insight into password creation strategies. As such, the model can be used as a tool for research and education. It can also be used by practitioners in, for instance, penetration testing to map the most used password creation strategies in a domain or by forensic experts when designing dictionary attacks.
From singular to plural: exploring organisational complexities and circular business model design
Authors: Pedersen Esben Rahbek Gjerdrum , Earley Rebecca , Andersen Kirsti Reitan
Published: June 2019

Purpose

The purpose of this paper is to discuss how organisational complexities influence the design of circular business models, which have recently been introduced as a new panacea for aligning the interests of business with the needs of the environment.

Design/methodology/approach

The Service Shirt, a new garment concept, is used as an illustrative case example for demonstrating some of the organisational complexities of making circular business models operable. The shirt was developed through a series of design workshops for the fashion brand Fashion Alpha.

Findings

The analysis highlights multiple challenges emerging when a fashion product with a significantly extended lifecycle passes through different users, organisations and business models. It is concluded that it is difficult to talk about a circular business model (singular) as circular economy solutions depend on the contributions of multiple stakeholders with business models.

Practical implications

The findings illustrate how fashion companies interested in the circular economy fundamentally have to rethink conventional approaches to value, organisational boundaries and temporality.

Originality/value

Drawing on a case example from the fashion industry, the paper demonstrates the organisational complexities linked to the design of new business models based on circular economy thinking, as these require the coordination of actions between autonomous actors driven by different logics regarding value creation, value delivery and value capture.
Association between long-term stressors and mental health distress following the 2013 Moore tornado: a pilot study
Authors: Clay Lauren A. , Greer Alex
Published: June 2019

Purpose

Stress has considerable impacts on human health, potentially leading to issues such as fatigue, anxiety and depression. Resource loss, a common outcome of disasters, has been found to contribute to stress among disaster survivors. Prior research focuses heavily on clinical mental health impacts of disaster experience, with less research on the effect of cumulative stress during long-term recovery. To address this gap, the purpose of this paper is to examine the influence of stressors including resource loss and debt on mental health in a sample of households in Moore, Oklahoma, impacted by a tornado in 2013.

Design/methodology/approach

For this pilot study, questionnaires were mailed to households residing along the track of the May 2013 tornado in Moore, OK. Descriptive statistics were calculated to report sample characteristics and disaster experience. Independent associations between disaster losses and demographic characteristics with the outcome mental health were examined withχ2and unadjusted logistic regression analysis. Adjusted logistic regression models were fit to examine resource loss and mental health.

Findings

Findings suggest that the tornado had considerable impacts on respondents: 56.24 percent (n=36) reported that their homes were destroyed or sustained major damage. Greater resource loss and debt were associated with mental health distress during long-term recovery from the Moore, OK, 2013 tornadoes.

Research limitations/implications

The association between resource loss and mental health point to a need for interventions to mitigate losses such as bolstering social support networks, incentivizing mitigation and reducing financial constraints on households post-disaster.

Originality/value

This study contributes to a better understanding of long-term, accumulated stress post-disaster and the impact on health to a literature heavily focused on clinical outcomes.
Pay-what-you-want with charitable giving positively impacts retailers
Authors: Fowler Kendra , Thomas Veronica L.
Published: June 2019

Purpose

The purpose of this paper is to investigate, from the perspective of a retailer, which of two philanthropy programs (pay-what-you-want [PWYW] with charitable giving or mere donation) results in more positive impressions of, and behavioral intentions toward, the retailer sponsoring the program.

Design/methodology/approach

Two studies investigate the influence of donation format (PWYW with charitable giving versus mere donation) on attitude and behavioral intentions toward the retailer, the second of which also explores equity as the mediating mechanism that produces the more favorable attitudes and intentions.

Findings

Results indicate that PWYW with charitable giving is effective at enhancing purchase intentions and attitudes toward the retailer. Specifically, results suggest that the implementation of a PWYW with charitable giving format leads to higher perceptions of equity, ultimately leading to more positive attitudes and higher purchase intentions toward the retailer as compared with a mere donation format. Alternative explanations are examined and ruled out.

Originality/value

To date, research predominantly examines PWYW with charitable giving from a pricing perspective and has yet to explore how it compares with other donation campaigns in terms of the impact on consumers’ attitudes and intentions toward the sponsoring retailer. This research fills that gap and contributes to the literature by broadening the perspective by which PWYW with charitable giving is examined. Managerially, the research is important, as it suggests that consumers consider the equity of various donation formats and think more favorably of retailers using more equitable donation campaigns.