bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractObesity 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 ABSTRACTSUMMARYBreast 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 SummaryRab11b 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

ABSTRACTIdentifying 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

AbstractFor 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

AbstractRotational 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

AbstractAccurate 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

AbstractThymic 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

AbstractRabies 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 summaryThe 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.
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

PurposeUsing 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/approachThe 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.FindingsThe 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/valueOn 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

PurposeThe 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/approachThe 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.FindingsThe 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 implicationsThe findings illustrate how fashion companies interested in the circular economy fundamentally have to rethink conventional approaches to value, organisational boundaries and temporality.Originality/valueDrawing 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

PurposeStress 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/approachFor 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.FindingsFindings 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/implicationsThe 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/valueThis 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.