bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuregulin1 nuclear signaling influences adult neurogenesis and regulates a schizophrenia susceptibility gene network within the mouse dentate gyrus
Authors: Rajebhosale Prithviraj , Jone Alice , Johnson Kory R. , Hofland Rohan , Palarpalar Camille , Khan Samara , Role Lorna W. , Talmage David A. 
Published: August 2022

ABSTRACTNeuregulin1 (Nrg1) signaling is critical for aspects of neuronal development and function from fate specification to synaptic plasticity. Type III Nrg1 is a synaptic protein which engages in bi-directional signaling with its receptor ErbB4. Forward signaling engages ErbB4 phosphorylation, whereas back signaling engages two known mechanisms: 1. local axonal PI3K-AKT signaling, and 2. cleavage by gamma secretase resulting in cytosolic release of the intracellular domain (ICD), which can traffic to the nucleus (Bao, Wolpowitz et al. 2003, Hancock, Canetta et al. 2008). To dissect the contribution of these alternate signaling strategies to neuronal development we generated a transgenic mouse with a missense mutation (V321L) in the Nrg1 transmembrane domain that disrupts nuclear back signaling with minimal effects on forward signaling or local back-signaling and was previously found to be associated with psychosis (Walss-Bass, Liu et al. 2006). We combined RNA sequencing, retroviral fate mapping of neural stem cells, behavioral analyses, and various network analyses of transcriptomic data to investigate the effect of disrupting Nrg1 nuclear back-signaling in the dentate gyrus (DG) of male and female mice.The V321L mutation impairs nuclear translocation of the Nrg1 ICD and alters gene expression in the DG. V321L mice show reduced stem cell proliferation, altered cell cycle dynamics, fate specification defects, and dendritic dysmorphogenesis. Orthologs of known schizophrenia (SCZ)-susceptibility genes were dysregulated in the V321L DG. These genes coordinated a larger network with other dysregulated genes. WGCNA and protein-interaction network analyses revealed striking similarity between DG transcriptomes of V321L mouse and humans with schizophrenia.SIGNIFICANCE STATEMENTSynaptic contact is predicted to be a regulator of the generation of nuclear signaling by Nrg1. Here we show that a schizophrenia-associated mutation in Nrg1 disrupts its ability to communicate extracellular signals to the neuronal genome which results in altered expression of a gene network enriched for orthologs of schizophrenia-susceptibility genes. The striking overlap in functional and molecular alterations between a single rare homozygous missense mutation (V321L) and schizophrenia patient data (complex polygenic and environmental burden) underscores potential convergence of rare and common variants on the same cellular and molecular phenotypes. Furthermore, our data indicate that the evolutionarily conserved gene networks that form the basis for this risk are necessary for coordinating neurodevelopmental events in the DG.
Piezo1 as a force-through-membrane sensor in red blood cells
Authors: Vaisey George , Banerjee Priyam , North Alison J. , Haselwandter Christoph A. , Mackinnon Roderick 
Published: August 2022

SummaryPiezo1 is the stretch activated Ca2+ channel in red blood cells that mediates homeostatic volume control. Here we study the organization of Piezo1 in red blood cells using a combination of super resolution microscopy techniques and electron microscopy. Piezo1 adopts a non- uniform distribution on the red blood cell surface, with a bias towards the biconcave “dimple”. Trajectories of diffusing Piezo1 molecules, which exhibit confined Brownian diffusion on short timescales and hopping on long timescales, also reflect a bias towards the dimple. This bias can be explained by “curvature coupling” between the intrinsic curvature of the Piezo dome and the curvature of the red blood cell membrane. Piezo1 does not form clusters with itself, nor does it co-localize with F-actin, Spectrin or the Gardos channel. Thus, Piezo1 exhibits the properties of a force-through-membrane sensor of curvature and lateral tension in the red blood cell.
Development of highly potent non-covalent inhibitors of SARS-CoV-2 3CLpro
Authors: Hou Ningke , Shuai Lei , Zhang Lijing , Xie Xuping , Tang Kaiming , Zhu Yunkai , Yu Yin , Zhang Wenyi , Tan Qiaozhu , Zhong Gongxun , Wen Zhiyuan , Wang Chong , He Xijun , Huo Hong , Gao Haishan , Xu You , Xue Jing , Peng Chen , Zou Jing , Schindewolf Craig , Menachery Vineet , Su Wenji , Yuan Youlang , Shen Zuyuan , Zhang Rong , Yuan Shuofeng , Yu Hongtao , Shi Pei-Yong , Bu Zhigao , Huang Jing , Hu Qi 
Published: August 2022

AbstractThe SARS-CoV-2 virus is the causal agent of the ongoing pandemic of coronavirus disease 2019 (COVID-19). There is an urgent need for potent, specific antiviral compounds against SARS-CoV-2. The 3C-like protease (3CLpro) is an essential enzyme for the replication of SARS-CoV-2 and other coronaviruses, and thus is a target for coronavirus drug discovery. Nearly all inhibitors of coronavirus 3CLpro reported so far are covalent inhibitors. Here, we report the development of specific, non-covalent inhibitors of 3CLpro. The most potent one, WU-04, effectively blocks SARS-CoV-2 replications in human cells with EC50 values in the 10-nM range. WU-04 also inhibits the 3CLpro of SARS-CoV and MERS-CoV with high potency, indicating that it is a pan-inhibitor of coronavirus 3CLpro. WU-04 showed anti-SARS-CoV-2 activity similar to that of PF-07321332 (Nirmatrelvir) in K18-hACE2 mice when the same dose was administered orally. Thus, WU-04 is a promising drug candidate for coronavirus treatment.One-Sentence SummaryA oral non-covalent inhibitor of 3C-like protease effectively inhibits SARS-CoV-2 replication.
E-cadherin/HMR-1 and PAR-3 break symmetry at stable cell contacts in a developing epithelium
Authors: Naturale Victor F. , Pickett Melissa A. , Feldman Jessica L. 
Published: August 2022

SummaryTissue-wide patterning is essential to multicellular development, requiring cells to individually generate polarity axes and coordinate them in space and time with neighbors. Using the C. elegans intestinal epithelium, we identified a patterning mechanism informed by stabilized cell/cell contact and executed via the scaffolding protein PAR-3 and the transmembrane protein E-cadherin/HMR-1. Intestinal cells break symmetry as PAR-3 and HMR-1 recruit apical determinants into micron-scale ‘local polarity complexes’ (LPCs) at homotypic contacts. LPCs undergo a HMR-1-based migration to a common tissue midline, thereby establishing tissue-wide polarity. Thus, symmetry breaking results from PAR-3-dependent intracellular polarization coupled to HMR-1-based tissue-level communication that occurs through a non-adhesive signaling role for HMR-1. Intestinal cells gain initial asymmetry from differential contact duration as homotypic contacts last longer than heterotypic contacts, thus providing stable platforms for LPC assembly and offering a logical and likely conserved framework for how internal epithelia with no obvious pre-existing asymmetries can polarize.
Dermal appendage-dependent patterning of zebrafish atoh1a+ Merkel cells
Authors: Brown Tanya L. , Horton Emma C. , Craig Evan W. , Hewitt Madeleine N. , Yee Nathaniel G. , Goo Camille E.A. , Fan Everett T. , Black Erik C. , Raible David W. , Rasmussen Jeffrey P. 
Published: August 2022

ABSTRACTTouch system function requires precise interactions between specialized skin cells and somatosensory axons, as exemplified by the vertebrate mechanosensory Merkel cell-neurite complex. Development and patterning of Merkel cells and associated neurites during skin organogenesis remains poorly understood, partly due to the in utero development of mammalian embryos. Here, we discover Merkel cells in the zebrafish epidermis and identify Atonal homolog 1a (Atoh1a) as a marker of zebrafish Merkel cells. We show that zebrafish Merkel cells derive from basal keratinocytes, express neurosecretory and mechanosensory machinery, extend actin-rich microvilli, and complex with somatosensory axons, all hallmarks of mammalian Merkel cells. Merkel cells populate all major adult skin compartments, with region-specific densities and distribution patterns. In vivo photoconversion reveals that Merkel cells undergo steady loss and replenishment during skin homeostasis. Merkel cells develop concomitant with dermal appendages along the trunk, and preventing dermal appendage formation reduces Merkel cell density by affecting both cell differentiation and maintenance. By contrast, altering dermal appendage morphology changes the distribution, but not density, of Merkel cells. Overall, our studies provide insights into touch system maturation during skin organogenesis and establish zebrafish as an experimentally accessible in vivo model for the study of Merkel cell biology.
Effect of baffles on hydrodynamic ram and damage of storage tank under fragment impact
Authors: Tang Yuxin , Liu Ang , Zhao Chen , Ren Peng , Guo Zitao 
Published: August 2022

Purpose
Fragment impact is one of the main threats for the safety of storage tank in aircraft. This study aims to investigate the influence of inserted baffle on hydrodynamic ram (HRAM) and damage of storage tank to optimize the protective performance of storage tank under fragment impact.

Design/methodology/approach
The characteristics of initial shock wave, cavity evolution, velocity attenuation of fragment and anti-penetration performance of baffle-inserted tanks were evaluated by experimental and numerical methods.

Findings
Results indicated that the inserted baffle in tank could significantly increase the velocity attenuation rate of fragment in water. The volume of the second cavity caused by the inserted baffle rapidly decreased with the baffle position moving backward. For the baffle-inserted tank, the deformation of the front and rear walls was substantially weakened, and the alleviating effect for front wall was more significant. Comparing with the ordinary storage tank, the inserted baffle at normalized position 0.25, 0.5 and 0.75 in tank made the ballistic limit velocity of storage tank increasing by 118.3%, 20.0% and 54.0%, respectively.

Originality/value
The findings of this work illustrating the HRAM history and damage map of storage tanks after inserted baffle could provide a convenient approach to improve the anti-penetration performance of storage tanks effectively.
Life cycle and metrics to measure the resilience of business processes by considering resources
Authors: Stocker Joachim , Herda Nils , Jürjens Jan 
Published: August 2022

PurposeEnterprises often face a wide variety of adverse events. Adverse events can have negative effects on organizations like failures of resources. In case resources fail, they are not available and cannot perform the assigned work. Enterprises are therefore especially interested in how resilient processes and workflows are in case adverse events occur and resources may fail. For this purpose, process resilience measurement approaches are needed.Design/methodology/approachTo measure the resilience of processes and workflows, a life cycle and five quantitative metrics have been developed. The metrics have been validated using five real-world production and logistics cases to show their applicability on process models and paths. Furthermore, workshops have been conducted with professionals to get additional feedback on the contributions.FindingsBased on the results obtained from applying the metrics to five real-world cases, view-based resilience improvements can be derived. Overall, only one of the five real-world cases can be considered as completely resilient. Furthermore, the metrics and life cycle have been especially valued by professionals with respect to transparency, independency, comparability as well as the ability to determine critical process paths.Originality/valueSeveral authors have dealt with different aspects related to the measurement of business processes, resilience or a combination thereof. However, a life cycle or metrics to quantitatively measure the resilience of processes by considering resources has not been found yet. The life cycle and metrics are therefore novel. As a future research direction, they can be applied in different domains for further validation purposes.
Topology optimization of shell-infill structures for natural frequencies
Authors: Liu Kang , Bai Yingchun , Yao Shouwen , Luan Shenggang 
Published: August 2022

PurposeThe purpose of this paper is to develop a topology optimization algorithm considering natural frequencies.Design/methodology/approachTo incorporate natural frequency as design criteria of shell-infill structures, two types of design models are formulated: (1) type I model: frequency objective with mass constraint; (2) type II model: mass objective with frequency constraint. The interpolation functions are constructed by the two-step density filtering approach to describe the fundamental topology of shell-infill structure. Sensitivities of natural frequencies and mass with respect to the original element densities are derived, which will be used for both type I model and type II model. The method of moving asymptotes is used to solve both models in combination with derived sensitivities.FindingsMode switching is one of the challenges faced in eigenfrequency optimization problems, which can be overcome by the modal-assurance-criterion-based mode-tracking strategy. Furthermore, a shifting-frequency-constraint strategy is recommended for type II model to deal with the unsatisfactory topology obtained under direct frequency constraint. Numerical examples are systematically investigated to demonstrate the effectiveness of the proposed method.Originality/valueIn this paper, a topology optimization method considering natural frequencies is proposed by the author, which is useful for the design of shell-infill structures to avoid the occurrence of resonance in dynamic conditions.
An association rule mining model for evaluating the potential correlation of construction cross operation risk
Authors: Chen Qianqian , Tian Zhen , Lei Tian , Huang Shenghan 
Published: August 2022

PurposeCross operation is a common operation method in the building construction process nowadays. Due to the crossover, each other's operations are disturbed, and risks also interact. This superimposed relationship of risks is worthy of attention. The study aims to develop a model for analyzing cross-working risks. This model can quantify the correlation of various risk factors.Design/methodology/approachThe concept of cross operation and the cross types involved are clarified. The risk factors were extracted from cross-operation accidents. The association rule mining (ARM) was used to analyze the results of various cross-types accidents. With the help of visualization tools, the intensity distribution and correlation path of the relationship between each factor were obtained. A complete cross-operation risk analysis model was established.FindingsThe application of ARM method proves that there are obvious risk correlation deviations in different types of cross operations. A high-frequency risk common to all cross operations is on-site safety inspection and process supervision, but the subsequent problems are different. Cutting off the high-lift risk chain timely according to the results obtained by ARM can reduce or eliminate the danger of high-frequency risk factors.Originality/valueThis is the first systematic analysis of cross-work risk in the construction. The study determined the priority of risk management. The results contribute to targeted cross-work control to reduce accidents caused by cross-work.
Entrepreneurial e-equity crowdfunding platforms: antecedents of knowledge acquisition and innovation performance
Authors: Alalwan Ali Abdallah , Baabdullah Abdullah M. , Mahfod Joma Omran , Jones Paul , Sharma Anshuman , Dwivedi Yogesh K. 
Published: August 2022

PurposeThe crowdfunding concept and activities have recently been the focus of attention of many researchers and practitioners over different business contexts. However, there is a dearth of literature considering the main aspects of e-equity crowdfunding activities and their impact on the innovation performance for entrepreneurial business. Therefore, this study aims to explore how entrepreneurs' engagement in e-crowdfunding activities could enhance both knowledge acquisition and innovation performance.Design/methodology/approachThe conceptual model will be proposed based on three main theoretical perspectives: relationship marketing orientation (RMO); Kirzner's alertness theory; and the DeLone and McLean model of information systems. The data of the current study were collected using an online questionnaire from a sample of 500 entrepreneurs who have actively engaged in e-crowdfunding in Saudi Arabia.FindingsThe statistical results of structural equation modelling (SEM) approved the impacting role of RMO, entrepreneurial alertness, system quality and service quality on the entrepreneurs' engagement in e-equity crowdfunding, which in turn, predicts both knowledge acquisition and innovation performance.Research limitations/implicationsThere are several limitations which could be addressed in future studies, for example, this study has only considered one form of crowdfunding (equity based crowdfunding) and due to its nature these findings would not be easily generalized to other kinds of crowdfunding (i.e. donation-based crowdfunding; rewards-based crowdfunding; and debt-based crowdfunding). Future studies could consider these kinds of crowdfunding activities.Originality/valueThis study has contributed to the understanding of e-equity crowdfunding in several aspects. For example, this study presents results that assist both researchers and practitioners in the Middle East and Saudi Arabia to develop an in-depth knowledge of e-equity crowdfunding by considering new dimensions such as RMO and information system success factors.
A quantitative study on utilizing electronic resources to engage children’s reading and learning: parents’ perspectives through the 5E instructional model
Authors: Cheung Lily Sin Nga , Chiu Dickson K.W. , Ho Kevin K.W. 
Published: August 2022

PurposeThis pilot study aims to investigate how parents use electronic resources to encourage children’s reading and learning interests through the 5E instructional model. Moreover, this study explores the public’s current electronic reading (e-reading) preferences, parents’ teaching process and the effectiveness of electronic resources in encouraging children to read and learn.Design/methodology/approachThis study used a quantitative research method with a 5- to 10-min online survey based on the 5E instructional model. A total of 101 respondents participated in the survey.FindingsTechnology has changed the public’s current e-reading preferences. More than 65% of parent respondents preferred to use the electronic reading format for their children’s teaching and learning. Parents generally agreed on the teaching and learning effectiveness of using electronic resources, especially for engaging their children. However, the parents showed no significant gender differences.Originality/valueThis pilot study is a new attempt to use the 5E instructional model to quantitatively analyse the parenting process of using electronic resources to encourage children to read and learn, especially in an Asian context.
Audit committee and impression management in financial annual reports: evidence from Jordan
Authors: Makhlouf Mohammed Hassan 
Published: August 2022

PurposeThe current paper aims at exploring the audit committee characteristics’ effect on impression management.Design/methodology/approachThe methodology is based on the use of the content analysis of financial annual reports, as data of a 69-company sample study from 2015 to 2019 attained from “Amman Stock Exchange” has been analyzed. Moreover, multiple regression analysis on panel data was employed.FindingsThe results show that the independence of the audit committee, the financial expertise of the audit committee and female members negatively affect impression management, implying that these characteristics mitigate financial reporting manipulation and decrease the practices of impression management. However, the findings detect no significant influence for committee meetings on impression management.Research limitations/implicationsNotably, the current work is applicable and useful for understanding the audit committee’s role in enhancing the financial reporting’s quality, along with the significance of the audit committee in growing the stakeholder’s confidence in financial reporting. In light of these results, regulatory bodies’ efforts are encouraged to create additional strategies and instructions to ensure the trustiness and credibility of financial reporting.Originality/valueThis paper will be useful to companies that want to improve the quality of financial reporting and decrease the impression of management’s effect on financial reporting’s readers. Moreover, this paper contributes to the literature on impression management by exploring the effect of audit committees on impression management of annual financial reports of the users in the context of emerging markets and Middle East countries, particularly Jordan.
The effects of GDL anisotropic transport properties on the PEFC performance
Authors: Okereke Isaac Chukwuemezu , Ismail Mohammed S. , Ingham Derek , Hughes Kevin J. , Ma Lin , Pourkashanian Mohamed 
Published: August 2022

PurposeThis paper aims to numerically investigate the impact of gas diffusion layer (GDL) anisotropic transport properties on the overall and local performance of polymer electrolyte fuel cells (PEFCs).Design/methodology/approachA three-dimensional numerical model of a polymer electrolyte fuel cell with a single straight channel has been developed to investigate the sensitivity of the fuel cell performance to the GDL anisotropic transport properties – gas permeability, diffusivity, thermal conductivity and electrical conductivity. Realistic experimentally estimated GDL transport properties were incorporated into the developed PEFC model, and a parametric study was performed to show the effect of these properties on fuel cell performance and the distribution of the key variables of current density and oxygen concentration within the cathode GDL.FindingsThe results showed that the anisotropy of the GDL must be captured to avoid overestimation/underestimation of the performance of the modelled fuel cell. The results also showed that the fuel cell performance and the distributions of current density and oxygen mass fraction within the cathode GDL are highly sensitive to the through-plane electrical conductivity of the GDL and, to a lesser extent, the through-plane diffusivity, and the thermal conductivity of the GDL. The fuel cell performance is almost insensitive to the gas permeability of the GDL.Practical implicationsThis study improves the understanding of the importance of the GDL anisotropy in the modelling of fuel cells and provides useful insights on improving the efficiency of the fuel cells.Originality/valueRealistic experimentally estimated GDL transport properties have been incorporated into the PEFC model for the first time, allowing for more accurate prediction of the PEFC performance.