bluuebunny/crossref_metadata_2025_split huggingface dataset:
Symmetry breaking during morphogenesis of a mechanosensory organ
Authors: Erzberger A. , Jacobo A. , Dasgupta A. , Hudspeth A. J. 
Published: July 2019

AbstractActively regulated symmetry breaking, which is ubiquitous in biological cells, underlies phenomena such as directed cellular movement and morphological polarization. Here we investigate how an organ-level polarity pattern emerges through symmetry breaking at the cellular level during the formation of a mechanosensory organ. Combining theory, genetic perturbations, and in vivo imaging assisted by deep learning, we study the development and regeneration of the fluid-motion sensors in the zebrafish’s lateral line. We find that two interacting symmetry-breaking events — one mediated by biochemical signaling and the other by cellular mechanics — give rise to a novel form of collective cell migration, which produces a mirror-symmetric polarity pattern in the receptor organ.
Variational autoencoders for cancer data integration: design principles and computational practice
Authors: Simidjievski Nikola , Bodnar Cristian , Tariq Ifrah , Scherer Paul , Andres-Terre Helena , Shams Zohreh , Jamnik Mateja , Liò Pietro 
Published: July 2019

ABSTRACTInternational initiatives such as the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) are collecting multiple data sets at different genome-scales with the aim to identify novel cancer bio-markers and predict patient survival. To analyse such data, several machine learning, bioinformatics and statistical methods have been applied, among them neural networks such as autoencoders. Although these models provide a good statistical learning framework to analyse multi-omic and/or clinical data, there is a distinct lack of work on how to integrate diverse patient data and identify the optimal design best suited to the available data.In this paper, we investigate several autoencoder architectures that integrate a variety of cancer patient data types (e.g., multi-omics and clinical data). We perform extensive analyses of these approaches and provide a clear methodological and computational framework for designing systems that enable clinicians to investigate cancer traits and translate the results into clinical applications. We demonstrate how these networks can be designed, built and, in particular, applied to tasks of integrative analyses of heterogeneous breast cancer data. The results show that these approaches yield relevant data representations that, in turn, lead to accurate and stable diagnosis.
Alpha-1 Antitrypsin Antisense Oligonucleotide Modulates Protease-Antiprotease Imbalance without Further Aggravating Smoke-induced Lung Injury
Authors: Xiao Rui , Stearns Kyle , Zelonina Tina , Goldklang Monica , Blomenkamp Keith , Teckman Jeffery , D’Armiento Jeanine 
Published: July 2019

AbstractAlpha-1 antitrypsin (AAT) is a serum protease inhibitor that prevents lung injury from protease production during cigarette smoking but causes severe liver disease once mutated. A custom AAT antisense oligonucleotide (ASO) was found to be beneficial for the AATD liver disease by blocking the mutated AAT transcripts. Here we hypothesized that knock-down of AAT aggravates murine lung injury during smoke exposure and acute exacerbations of chronic obstructive pulmonary disease (COPD). C57BL/6J mice were randomly divided into 4 groups for each of the injury models, smoking (inhale for 3 months at 150mg/m3) and smoke-flu (inhale for 2 weeks and intranasal influenza virus). The ASO and control (No-ASO) were injected subcutaneously at 10ml/kg of body weight, starting with smoking or four days prior to influenza infection weekly at 50mg/kg. ASO treatment during a 3 month smoke exposure significantly increased the expression of Cela1 mRNA and decreased the serum and lung AAT expression. However, despite the decrease in AAT, neither the inflammatory cell counts in the bronchoalveolar lavage fluid (BALF) nor the lung structural changes were significantly affected by ASO treatment. We observed significant differences in inflammation and emphysema due to smoke exposure alone. With the smoke-flu model, similarly the major differences were found between smoke-flu and room air control, with no additional effect with ASO treatment. Off-target effects or compensatory mechanisms may account for this finding. Alternatively, the reduction of AAT with ASO treatment was not robust enough to lead to lung injury. The result also suggest that the AAT ASO approach for treating liver disease is relatively safe at the specified dose as it did not lead to detrimental outcomes in the lung. These potential mechanisms need to be further investigated in order to fully understand the impact of AAT inhibition on protease-antiprotease imbalance in the murine smoke exposure model.
Immune responses in mice induced by multi-epitope DNA vaccine and protein vaccine of Crimean-Congo Hemorrhagic Fever Virus
Authors: Yusufu Meilipaiti , Shalitanati Alai , Yu Huan , Moming Abulimiti , Li Yijie , Deng Fei , Zhang Yujiang , Sun Surong 
Published: July 2019

AbstractCrimean-Congo Hemorrhagic Fever (CCHF), caused by the CCHF virus (CCHFV), is a severe tick borne zoonosis widely distributed in over 30 countries and regions. Currently, there is no licensed vaccine available for CCHF in China. To evaluate the cellular and humoral immune responses induced by multi-epitope DNA and protein vaccine of CCHF in BALB/c mice, a multi-epitope gene (MEPX) segment with tandem including six highly conservative and immunedominant B cell epitopes was designed based on the analysis of hydrophilicity and antigenic determinant sites in amino acid sequences of nucleoprotein and glycoprotein from CCHFV strain YL04057. The single and double-copy multi-epitope gene (MEPX and MEPX2) were respectively cloned into the eukaryotic expression vector pVAX I to construct the recombinant (r) plasmid pVAX-MEPX and pVAX-MEPX2as DNA vaccines. The results of immunofluorescence in vitro showed that the pVAX-MEPX and pVAX-MEPX2could be expressed in 293T cells. The recombinant prokaryotic plasmid pET-32a-MEPX and pET-32a-MEPX2constructed previously were transformed them intoE. coli BL21 (DE3), and recombinant multi-epitope proteins (rMEPX and rMEPX2) were obtained and purificated by Nickel affinity chromatography. Western blot results showed that rMEPX and rMEPX2had good antigenicity. BALB/c mice were immunized with DNA vaccine alone, protein vaccine alone, and DNA prime followed by recombinant protein boost immunization strategy, respectively. After three immunizations, MTT assay, cytokine content assay, and ELISA assay for antibody titers were used to evaluate the immune response. The proliferation of mouse specific T lymphocytes in the enhanced by pVAX-MEPX2combined with rMEPX2boosting group was significant, and the expression levels of serum IFN-γ and IL-4 in mice were as high as 118.67 pg/mL and 135.33 pg/mL with significant difference compared to the control group (p<0.01), and serum antibody titer could reach up to 4.1×105. Double-copy multi-epitope vaccines groups (pVAX-MEPX2+ rMEPX2) generated better cellular and humoral immune responses by DNA prime-protein vaccine boost combinatorial immunization. This result could lay the foundation for the development of CCHFV multi-epitope vaccine candidates.
Shigella sonneiinfection of zebrafish reveals that O-antigen mediates neutrophil tolerance and dysentery incidence
Authors: Torraca Vincenzo , Kaforou Myrsini , Watson Jayne , Duggan Gina M. , Guerrero-Gutierrez Hazel , Krokowski Sina , Hollinshead Michael , Clarke Thomas B. , Mostowy Rafal J. , Tomlinson Gillian S. , Sancho-Shimizu Vanessa , Clements Abigail , Mostowy Serge 
Published: July 2019

AbstractShigella flexneriis historically regarded as the primary agent of bacillary dysentery, yet the closely-relatedShigella sonneiis replacingS. flexneri, especially in developing countries. The underlying reasons for this dramatic shift are mostly unknown. Using a zebrafish (Danio rerio) model ofShigellainfection, we discover thatS. sonneiis more virulent thanS. flexneri in vivo. Whole animal dual-RNAseq and testing of bacterial mutants suggest thatS. sonneivirulence depends on its O-antigen oligosaccharide (which is unique amongShigellaspecies). We showin vivousing zebrafish andex vivousing human neutrophils thatS. sonneiO-antigen can mediate neutrophil tolerance. Consistent with this, we demonstrate that O-antigen enablesS. sonneito resist phagolysosome acidification and promotes neutrophil cell death. Chemical inhibition or promotion of phagolysosome maturation respectively decreases and increases neutrophil control ofS. sonneiand zebrafish survival. Strikingly, larvae primed with a sublethal dose ofS. sonneiare protected against a secondary lethal dose ofS. sonneiin an O-antigen-dependent manner, indicating that exposure to O-antigen can train the innate immune system againstS. sonnei. Collectively, these findings reveal O-antigen as an important therapeutic target against bacillary dysentery, and may explain the rapidly increasingS. sonneiburden in developing countries.Author SummaryShigella sonneiis predominantly responsible for dysentery in developed countries, and is replacingShigella flexneriin areas undergoing economic development and improvements in water quality. UsingShigellainfection of zebrafish (in vivo) and human neutrophils (in vitro), we discover thatS. sonneiis more virulent thanS. flexneribecause of neutrophil tolerance mediated by its O-antigen oligosaccharide acquired from the environmental bacteriaPlesiomonas shigelloides. To inspire new approaches forS. sonneicontrol, we show that increased phagolysosomal acidification or innate immune training can promoteS. sonneiclearance by neutrophilsin vivo. These findings have major implications for our evolutionary understanding ofShigella, and may explain why exposure toP. shigelloidesin low and middle-income countries (LMICs) can protect against dysentery incidence.
THOC1 deficiency leads to late-onset nonsyndromic hearing loss through p53-mediated hair cell apoptosis
Authors: Zhang Luping , Gao Yu , Zhang Ru , Sun Feifei , Cheng Cheng , Qian Fuping , Duan Xuchu , Wei Guanyun , Pang Xiuhong , Chen Penghui , Chai Renjie , Yang Tao , Wu Hao , Liu Dong 
Published: July 2019

AbstractApoptosis of cochlear hair cells is a key step towards age-related hearing loss. Although numerous genes have been implicated in the genetic causes of late-onset, progressive hearing loss, few show direct links to the proapoptotic process. By genome-wide linkage analysis and whole exome sequencing, we identified a heterozygous p.L183V variant in THOC1 as the probable cause of the late-onset, progressive, non-syndromic hearing loss in a large dominant family. Thoc1, a member of the conserved multisubunit THO/TREX ribonucleoprotein complex, is highly expressed in mouse and zebrafish hair cells. The Thoc1 mutant zebrafish generated by gRNA-Cas9 system lacks the C-startle response, indicative of the hearing dysfunction. Both Thoc1 mutant and knockdown zebrafish have greatly reduced hair cell numbers, while the latter can be rescued by embryonic microinjection of human wild-type THOC1 mRNA but to significantly lesser degree by the p.L183V mutant mRNA. The Thoc1 deficiency resulted in marked apoptosis in zebrafish hair cells. Consistently, transcriptome sequencing of the mutants showed significantly increased gene expression in the p53-associated signaling pathway. Depletion of p53 or applying the p53 inhibitor Pifithrin-α significantly rescued the hair cell loss in the Thoc1 knockdown zebrafish. Our results suggested that THOC1 deficiency lead to late-onset, progressive hearing loss through p53-mediated hair cell apoptosis. This is to our knowledge the first human disease associated with THOC1 mutations and may shed light on the molecular mechanism underlying the age-related hearing loss.Significance StatementFor the first time, we found that THOC1 deficiency leads to late-onset nonsyndromic hearing loss. Furthermore, we revealed the hypomorphic THOC1 induced p53-mediated hair cell apoptosis. This is to our knowledge the first human disease associated with THOC1 mutations and may shed light on the molecular mechanism underlying the age-related hearing loss.
Di-μ-acetato-bis{[3-benzyl-1-(2,4,6-trimethylphenyl)imidazol-2-ylidene]silver(I)}
Authors: Jayaraman Selvakumar , Castillo Guel Roberto Alexander , Malek Kotiba , Arumugam Kuppuswamy 
Published: July 2019

The title compound, [Ag2(C2H3O2)2(C19H20N2)2] (2), was readily synthesized by treatment of 3-benzyl-1-(2,4,6-trimethylphenyl)imidazolium chloride with silver acetate. The solution structure of the complex was analyzed by NMR spectroscopy, while the solid-state structure was confirmed by single-crystal X-ray diffraction studies. Compound 2 crystallizes in the triclinic space group P\overline{1}, with a silver-to-carbene bond length (Ag—CNHC) of 2.084 (3) Å. The molecule resides on an inversion center, so that only half of the molecule is crystallographically unique. The planes defined by the two imidazole rings are parallel to each other, but not coplanar [interplanar distance is 0.662 (19) Å]. The dihedral angles between the imidazole ring and the benzyl and mesityl rings are 77.87 (12) and 72.86 (11)°, respectively. The crystal structure features π–π stacking interactions between the benzylic groups of inversion-related (−x + 1, −y + 1, −z + 1) molecules and C—H...π interactions.
Does the chief audit executive gender matter to internal audit effectiveness? Evidence from Tunisia
Authors: Oussii Ahmed Atef , Klibi Mohamed Faker 
Published: July 2019

Purpose
The purpose of this paper is to investigate whether chief audit executive (CAE) gender has a significant impact on the internal audit function (IAF) effectiveness as proxied by the extent to which the internal audit function uses quality assurance techniques.

Design/methodology/approach
This study uses a multivariate regression model to analyze the association between CAE gender and the use of quality assurance techniques in fieldwork as a proxy for IAF effectiveness. Data were collected using a survey of 74 internal auditors from Tunisian listed companies.

Findings
The results indicate that IAFs run by a female CAE are more likely to incorporate quality assurance techniques into fieldwork than IAFs run by male CAEs. Therefore, internal audit departments managed by women tend to be more effective.

Practical implications
Findings highlight to regulators and reform advocates the importance of having women on the CAE position will improve internal audit practices’ quality. Thus, the gender difference in internal auditing should be more strongly emphasized in different cultural and economic contexts.

Originality/value
This study provides new insights which add to the existing gender literature by introducing a North African perspective and simultaneously providing new insights that highlight the importance of having women on top management positions in internal auditing and the positive effects which come with it.
The role of seafood sustainability knowledge in seafood purchase decisions
Authors: Lawley Meredith , Craig Jane F. , Dean David , Birch Dawn 
Published: July 2019

PurposeThe purpose of this paper is to explore consumer knowledge of seafood sustainability and how that knowledge influences the purchase of seafood products.Design/methodology/approachUsing an online survey (n=1,319), the authors investigated Australian consumer knowledge of seafood sustainability and the drivers of purchase choice. Objective knowledge categories were developed through the qualitative analysis of unprompted, open-ended responses and compared with other surveyed measures of objective knowledge. The relationship between these knowledge categories and the importance of sustainability in the purchase decision was tested.FindingsA significant group of consumers either had no knowledge of seafood sustainability (17.8 per cent) or gave an incorrect response (15.5 per cent), while 25.1 per cent demonstrated simple and 41.6 per cent complex knowledge. Further, the knowledge was positively related to importance of sustainability when making purchase decisions. Sustainability moved from the lowest ranked attribute for the no knowledge group to the highest ranked attribute for the complex knowledge group.Research limitations/implicationsThe results show that the consumer knowledge about sustainable seafood cannot be assumed and that the level of sustainability knowledge influences the importance of sustainability in the purchase decision.Practical implicationsThe results suggest that information-based strategies based on a universally shared definition of sustainability in the seafood industry designed to drive sustainable consumer behaviour for seafood must take the account of consumer knowledge.Originality/valueThis paper identifies and provides a classification framework for levels of consumer knowledge about sustainable seafood and demonstrates a positive relationship between knowledge and the importance of sustainability in consumer decisions with regard to purchasing seafood.
Forewarned is forearmed
Authors: Bharathi S. Vijayakumar 
Published: July 2019

Purpose
Internet of Things (IoT) interconnects many heterogeneous devices to each other, collecting and processing large volumes of data for decision making without human intervention. However, the information security concern it brings has attracted quite a lot of attention, and, at this stage, the smart step would be to analyze the security issues of IoT platform and get to the state of readiness before embarking upon this attractive technology. The purpose of this paper is to address these issues.

Design/methodology/approach
IoT risk assessment through the application of the analytical hierarchy process (AHP), a favorite multi-criteria decision making technique, is proposed. The IoT risks are prioritized and ranked at different layers, before which a well-defined IoT risk taxonomy is defined comprising of 25 risks across six layers of the IoT model for developing control and mitigation plans for information security of IoT.

Findings
People and processes layer, network layer and applications layer are the top three critical layers with risks like the lack of awareness, malware injection, malicious code injection, denial of service and inefficient policies for IoT practice get the highest priority and rank. Pareto analysis of the overall risk factors revealed that the top ten factors contribute to 80 percent of the risks perceived by information security experts.

Research limitations/implications
The study focuses only on certain predefined constructs or layers of the IoT model traced from legacy studies. It is essential to re-look these constructs on a timely basis to prolong the results’ validity. The study’s empirical scope is confined only to the risk perception of select IoT experts and does not encompass a broader segment of the IoT ecosystem. Therefore, the risks assessment may not be sweeping to a bigger audience.

Practical implications
The study implications are two-fold: one it consolidates the earlier siloed works to intensify the need for risk assessment in the IoT domain, and second the study brings yet another contextual avenue of extending the application AHP and Pareto principle combination. The paper also draws specific critical organizational interventions about IoT risks. A comprehensive approach to prioritizing and ranking IoT risks are present in this research paper.

Originality/value
The contribution of this study to the benchmarking of IoT risk assessment is two-fold. One, a comprehensive risk assessment taxonomy is proposed, and two, the risks are prioritized and ranked to give a convincing reference for the organizations while making information security plans for IoT technology.
Industry 4.0: key findings and analysis from the literature arena
Authors: G. Rejikumar , Sreedharan V. Raja , P. Arunprasad , Persis Jinil , K.M. Sreeraj 
Published: July 2019

Purpose
In recent years, a new transformation known as Industry 4.0 has drawn much attention throughout the world, and numerous investigations have fundamentally looked into the uprising concept. However, few have concentrated on the literature review. Taking this as motivation, the authors endeavored to assess the different attributes of Industry 4.0. The paper aims to discuss these issues.

Design/methodology/approach
This review concentrated on linking the articles from different database and distinguishing the attributes of Industry 4.0. The authors assessed 85 articles from scholarly database and peer-reviewed journals on Industry 4.0 through the selection of the Mayring (2004) procedure. The examination included a four-advance process, in particular, material gathering, engaging investigation, classification of the choice and material assessment.

Findings
The study backs experts and readers to comprehend the spread of Industry 4.0 in various ventures. For academicians, this gives an extensive rundown of Industry 4.0 attributes. Besides, the writing review gives a chance to comprehend the idea of Industry 4.0 in detail. Further, the outcome aggregates the success factor, failure factor, business model, potential and difficulties in the context of Industry 4.0.

Research limitations/implications
Many areas such as supply chain, circular economy and healthcare have started exploring Industry 4.0. However, few specific cases have reported about it, and no generic model is found for real-time application.

Practical implications
The study serves as reference material for researchers and practitioners to understand the spread of Industry 4.0 and utilize the concept of Industry 4.0 for real-life application.

Originality/value
The study focuses on reporting the potential, challenges, business model and pre-requites of Industry 4.0.