bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Nerve Growth Factor IB-like Receptor Nurr1 (NR4A2) Recruits CoREST Transcription Repressor Complexes to Silence HIV Following Proviral Reactivation in Microglial Cells
Authors: Ye Fengchun , Alvarez-Carbonell David , Nguyen Kien , Valadkhan Saba , Leskov Konstantin , Garcia-Mesa Yoelvis , Sreeram Sheetal , Karn Jonathan 
Published: November 2021

ABSTRACTHuman immune deficiency virus (HIV) infection of microglial cells in the brain leads to chronic neuroinflammation, which is antecedent to the development of HIV-associated neurocognitive disorders (HAND) in the majority of patients. Productively HIV infected microglia release multiple neurotoxins including proinflammatory cytokines and HIV proteins such as envelope glycoprotein (gp120) and transactivator of transcription (Tat). However, powerful counteracting silencing mechanisms in microglial cells result in the rapid shutdown of HIV expression to limit neuronal damage. Here we investigated whether the Nerve Growth Factor IB-like nuclear receptor Nurr1 (NR4A2), which is a repressor of inflammation in the brain, acts to directly restrict HIV expression. HIV silencing was substantially enhanced by Nurr1 agonists in both immortalized human microglial cells (hµglia) and induced pluripotent stem cells (iPSC)-derived human microglial cells (iMG). Overexpression of Nurr1 led to viral suppression, whereas by contrast, knock down (KD) of endogenous Nurr1 blocked HIV silencing. Chromatin immunoprecipitation (ChIP) assays showed that Nurr1 mediates recruitment of the CoREST/HDAC1/G9a/EZH2 transcription repressor complex to HIV promoter resulting in epigenetic silencing of active HIV. Transcriptomic studies demonstrated that in addition to repressing HIV transcription, Nurr1 also downregulated numerous cellular genes involved in inflammation, cell cycle, and metabolism, thus promoting HIV latency and microglial homoeostasis. Thus, Nurr1 plays a pivotal role in modulating the cycles of proviral reactivation by cytokines and potentiating the proviral transcriptional shutdown. These data highlight the therapeutic potential of Nurr1 agonists for inducing HIV silencing and microglial homeostasis and amelioration of the neuroinflammation associated with HAND.AUTHOR SUMMARYHIV enters the brain almost immediately after infection where it infects perivascular macrophages, microglia and, to a less extent, astrocytes. In previous work using an immortalized human microglial cell model, we observed that integrated HIV constantly underwent cycles of reactivation and subsequent silencing. In the present study, we found that the Nurr1 nuclear receptor is a key mediator of HIV silencing. The functional activation of Nurr1 by specific agonists, or the over expression of Nurr1, resulted in rapid silencing of activated HIV in microglial cells. Global gene expression analysis confirmed that Nurr1 not only repressed HIV expression but also regulated numerous genes involved in microglial homeostasis and inflammation. Thus, Nurr1 is pivotal for HIV silencing and repression of inflammation in the brain and is a promising therapeutic target for treatment of HAND.
Binding stoichiometry and structural model of the HIV-1 Rev/Importin β complex
Authors: Spittler Didier , Indorato Rose-Laure , Erba Elisabetta Boeri , Delaforge Elise , Signor Luca , Harris Simon J. , Garcia-Saez Isabel , Palencia Andrés , Gabel Frank , Blackledge Martin , Noirclerc-Savoye Marjolaine , Petosa Carlo 
Published: November 2021

ABSTRACTHIV-1 Rev mediates the nuclear export of intron-containing viral RNA transcripts and is essential for viral replication. Rev is imported into the nucleus by the host protein Importin β (Impβ), but how Rev associates with Impβ is poorly understood. Here we report biochemical, biophysical and structural studies of the Impβ/Rev complex. Gel shift, native mass spectrometry and isothermal titration calorimetry data reveal that Impβ binds two Rev monomers through independent binding sites. Small-angle X-ray scattering (SAXS) data suggest that the HEAT repeats of Impβ retain an extended conformation upon binding Rev, which according to NMR data is primarily recognized through its helical hairpin domain. Peptide scanning data and charge-reversal mutations identify the N-terminal tip of Rev helix α2 within Rev’s Arginine-Rich Motif (ARM) as a primary Impβ binding epitope. Crosslinking mass spectrometry and compensatory mutagenesis data combined with molecular docking simulations suggest a structural model in which one Rev monomer binds to the C-terminal half of Impβ with Rev helix α2 roughly parallel to the HEAT-repeat superhelical axis while the other monomer binds to the N-terminal half. These findings shed light on the molecular basis of Rev recognition by Impβ and highlight an atypical binding behaviour that distinguishes Rev from canonical cellular Impβ cargos.
piCRISPR: Physically Informed Deep Learning Models for CRISPR/Cas9 Off-Target Cleavage Prediction
Authors: Störtz Florian , Mak Jeffrey , Minary Peter 
Published: November 2021

AbstractCRISPR/Cas programmable nuclease systems have become ubiquitous in the field of gene editing. With progressing development, applications inin vivotherapeutic gene editing are increasingly within reach, yet limited by possible adverse side effects from unwanted edits. Recent years have thus seen continuous development of off-target prediction algorithms trained onin vitrocleavage assay data gained from immortalised cell lines. It has been shown that in contrast to experimental epigenetic features, computed physically informed features are so far underutilised despite bearing considerably larger correlation with cleavage activity. Here, we implement state-of-the-art deep learning algorithms and feature encodings for off-target prediction with emphasis onphysically informedfeatures that capture the biological environment of the cleavage site, hence terming our approach piCRISPR. Features were gained from the large, diverse crisprSQL off-target cleavage dataset. We find that our best-performing models highlight the importance of sequence context and chromatin accessibility for cleavage prediction and compare favourably with literature standard prediction performance. We further show that our novel, environmentally sensitive features are crucial to accurate prediction on sequence-identical locus pairs, making them highly relevant for clinical guide design. The source code and trained models can be found ready to use at github.com/florianst/picrispr.
Structure of the rabies virus glycoprotein trimer bound to a pre-fusion specific neutralizing antibody
Authors: Callaway Heather M. , Zyla Dawid , Hastie Kathryn M. , Avalos Ruben Diaz , Agarwal Alyssa , Bourhy Hervé , Corti Davide , Saphire Erica Ollmann 
Published: November 2021

AbstractRabies infection is nearly 100% lethal if untreated and kills over 50,000 people annually, many of them children. Existing rabies vaccines target the rabies virus glycoprotein (RABV-G) but generate short-lived immune responses, likely because the protein is heterogeneous under physiological conditions. Here, we report the 3.39Å cryo-EM structure of trimeric, pre-fusion RABV-G complexed with RVA122, a potently neutralizing human antibody. RVA122 binds to a quaternary epitope at the top of RABV-G, bridging domains and stabilizing RABV-G protomers in a prefusion state. RABV-G trimerization involves side-to-side interactions between the central α-helix and adjacent loops, rather than contacts between central helices, and interactions among the fusion loops at the glycoprotein base. These results provide a basis to develop improved rabies vaccines based on RABV-G stabilized in the prefusion conformation.One sentence summaryWe report the structure and trimeric interface of pre-fusion rabies virus glycoprotein bound to the neutralizing antibody RVA122.
Experiences of information literacy and mobile technologies amongst undergraduates in times of COVID. A qualitative approach
Authors: Pinto Maria , Caballero Mariscal David , Segura Alicia 
Published: November 2021

PurposeThe purpose of this article is to analyse the social science students' perceptions of information literacy (IL) and the use of mobile technologies (MTs) before and during the COVID-19 pandemic.Design/methodology/approachExploratory focus group methodology involving 18 Information Science and Education undergraduates.FindingsStudents believe that, above all, an information literate person must know how to search for information. Being able to recognise acceptable levels of IL and MT competencies/skills enabled them to detect the scant contribution of the university to IL and the poor support from the library. They routinely use information and communication technologies (ICTs) in the classroom for assignments, presentations, searching and administrative tasks. Conversely, they consider their teachers' competency in the use of mobile devices for academic tasks could be improved. The increase in these shortcomings during the COVID-19 pandemic has allowed students to discover most teachers' attitudinal and technical limitations. Students' suggestions mostly point to improving platforms, teaching methods, teacher motivation and teachers/librarians interaction.Research limitations/implicationsResearch is limited to several IL/MT-related concepts, one university and two degrees. It could be applied in other contexts, larger samples and other stakeholders such as librarians and teachers.Practical implicationsNeed for more IL and TM instruction for students/teachers and greater interaction amongst them and with the library. The authors suggest promoting interdisciplinary seminars on the importance of IL and awareness sessions on ICT for learning.Originality/valueThis case study addresses students' critical/exceptional experience triggered by the pandemic.
Comparative assessments of strain measures for nonlinear analysis of truss structures at large deformations
Authors: Greco Marcelo , Peixoto Daniel Henrique Nunes 
Published: November 2021

PurposeIn this paper the use of classical strain measures in analysis of trusses at finite deformations will be discussed. The results will be compared to the ones acquired using a novel strain measure based on the Hyperbolic Sine function. Through the evaluation of results, algebraic development and graph analysis, the properties of the Hyperbolic Sine strain measure will be examined.Design/methodology/approachThrough graph plotting, comparisons between the novel strain measure and the classic ones will be made. The formulae for the implementation of the Hyperbolic Sine strain measure into a positional finite element method are developed. Four engineering applications are presented and comparisons between results obtained using all strain measures studied are made.FindingsThe proposed strain measure, Hyperbolic Sine, has objectivity and symmetry. The linear constitutive model formed by the Hyperbolic Sine strain and its conjugated stress presents an increasing stiffness, both in compression and tension, a behavior that can be useful in the modeling of several materials.Research limitations/implicationsThe structural analysis performed on the four examples of trusses in this article did not consider the variation of the cross-sectional area of the elements or the buckling phenomenon, moreover, only elastic behavior is considered.Originality/valueThe present article proposes the use of a novel strain measure family, based on the Hyperbolic Sine function and suitable for structural applications. Mathematical expressions for the use of the Hyperbolic Sine strain measure are established following the energetic concepts of the positional formulation of the finite element method.
The impact of gender inequality in education and employment on economic performance in Turkey: evidence from a cointegration approach
Authors: Esen Ömer , Seren Gamze Yıldız 
Published: November 2021

PurposeThis study aims to empirically examine the impact of gender-based inequalities in both education and employment on economic performance using the dataset of Turkey for the period 1975–2018.Design/methodology/approachThis study employs Johansen cointegration tests to analyze the existence of a long-term relation among variables. Furthermore, dynamic ordinary least squares (DOLS) and fully modified ordinary least squares (FMOLS) estimation methods are performed to determine the long-run coefficients.FindingsThe findings from the Johansen cointegration analysis confirm that there is a long-term cointegration relation between variables. Moreover, DOLS and FMOLS results reveal that improvements in gender equality in both education and employment have a strong and significant impact on real gross domestic product (GDP) per capita in the long term.Originality/valueThe authors expect that this study will make remarkable contributions to the future academic studies and policy implementation, as it examines the relation among the variables by including the school life expectancy from primary to tertiary based on the gender parity index (GPI), the gross enrollment ratio from primary to tertiary based on GPI and the ratio of female to male labor force participation (FMLFP) rate.
Assessing the performance of Islamic banks in Malaysia based on balanced scorecard (BSC) measures and Shari'ah guidelines compliance
Authors: Abueid Raed 
Published: November 2021

PurposeIslamic banking sector is gaining popularity globally. However, in recent decades, Malaysia's Islamic banking sector has been reckoned as an influential force in the global economy and became a rapidly growing industry. In fact, the international banking industry has admitted Malaysia as the leading Islamic banking center with the most progressive and attractive planning, strategic directions of development, and numerous incentives for nurturing this sector. Hence, this paper aims to evaluate the performance of Islamic banks in Malaysia based on Balanced Scorecard (BSC) measures and Shari'ah Guidelines Compliance.Design/methodology/approachTo achieve the objectives of this paper, BSC performance evaluation system and Shari'ah Guidelines Compliance were used based on the data collected through an online poll survey across Malaysian Islamic banks from an aggregate of 994 information focused on 71 items, using 14 respondents in which ten were from the regional level and four were from the headquarters of the bank. Furthermore, nine respondents were bank managers and five were bank employees.FindingsThe findings of the paper are as follows: First, there is a useful connection among BSC estimates, attributes of Shari’ah Compliance and Islamic banks' performance. Second, tremendous improvement has been seen in the Malaysian Islamic banks, which used both the BSC measures and Shari'ah Guidelines Compliance.Practical implicationsThe practical implication of the findings is that utilizing the BSC count and Shari’ah consistence characteristics; Islamic banks can better their exhibition and therefore, the banks ought to receive the recorded down rules alongside the BSC measures and Shari'ah ascribes to accomplish a superior presentation, benefit and achievement of Islamic currency advertise.Originality/valueThe novelty/originality of this paper can be seen from the fact that despite the BSC becoming a widely used performance management tool; still, there is a deficiency of standardization between a company and its perception of the term BSC and also mostly, research works on BSC were carried out on the United States- and European-based organizations, but in Malaysia, nothing more was done, especially in the Islamic banking sector, while this model is capable of covering both economic and non-economic estimate of presentation and therefore, considered as a sophisticated presentation computation system for performance evaluation.
Design of low power SRAM- based ubiquitous sensor for wireless body area networks
Authors: Neeraj Kumar , Mahaboob Basha Mohammed , Gundala Srinivasulu 
Published: November 2021

Purpose
Smart ubiquitous sensors have been deployed in wireless body area networks to improve digital health-care services. As the requirement for computing power has drastically increased in recent years, the design of low power static RAM-based ubiquitous sensors is highly required for wireless body area networks. However, SRAM cells are increasingly susceptible to soft errors due to short supply voltage. The main purpose of this paper is to design a low power SRAM- based ubiquitous sensor for healthcare applications.

Design/methodology/approach
In this work, bias temperature instabilities are identified as significant issues in SRAM design. A level shifter circuit is proposed to get rid of soft errors and bias temperature instability problems.

Findings
Bias Temperature Instabilities are focused on in recent SRAM design for minimizing degradation. When compared to the existing SRAM design, the proposed FinFET-based SRAM obtains better results in terms of latency, power and static noise margin. Body area networks in biomedical applications demand low power ubiquitous sensors to improve battery life. The proposed low power SRAM-based ubiquitous sensors are found to be suitable for portable health-care devices.

Originality/value
In wireless body area networks, the design of low power SRAM-based ubiquitous sensors are highly essential. This design is power efficient and it overcomes the effect of bias temperature instability.
Reliability analysis of a small solar system for a home
Authors: Musa Ismail Muhammad , Yusuf Ibrahim 
Published: November 2021

PurposeThe purpose of this paper is to model and to improve the stability and long-lasting operation of the small home solar system configuration regarding the reliability, availability, sensitivity, cost analysis and mean time to failure (MTTF).Design/methodology/approachA model of a small home solar system is designed in this write up. It is designed in a series–parallel configuration, such that four panels are arranged in parallel, working under 1-out-of-4: G; policy and two batteries configured in parallel also, working under 1-out-of-2: G; policy. The panels are connected to a charge controller, then to the batteries and lastly to an inverter, all connected together in series configuration. Different types of system reliability such as reliability, sensitivity, availability, MTTF and cost analysis for particular values of the failure and repair rates have been evaluated by using a supplementary variable and Laplace transforms and demonstrated the computed results on tables and graphs. The main objective here is to improve the stability and long-lasting operation of the small solar system configuration regarding the reliability, availability, sensitivity, cost analysis and MTTF.FindingsThe future behavior of the small solar system and similar systems can be easily predicted at any given time for any parametric values, it is also better to provide repair than replacements in the system for better availability and reliability, it signifies that γp, γb, γc and γi are responsible for the better performance of the system, the variation of sensitivity together with the parametric values variations and lastly deduced that the profit will decrease whenever service cost increase.Originality/valueThis paper provides a model of small home solar system and its reliability analysis.
Improving knowledge transfer through enterprise social media: the mediating role of transactive memory
Authors: Sun Yuan , Shang Rong-An , Cao Haiyang , Jiang Hongyu , Boehnke Klaus , Fu Jindi 
Published: November 2021

PurposeEnterprise social media can be the organizational transactive memory in which the knowledge dialogue provides users with the metaknowledge to support knowledge transfer. The purpose of this study is to examine a mediation model to show how perceived critical mass, openness and affiliation climate affect organizational knowledge transfer through the mediation of improving the metaknowledge of who knows what and whom.Design/methodology/approachTo test the mediation model and corresponding hypotheses, this study employs structural equation modeling analysis using 264 valid questionnaires.FindingsThe study found the two mediators fully explained the effects of the three preconditions on knowledge transfer.Originality/valueThese results help us to better understand the benefits of enterprise social media and the functions of transactive memory in organizations.
Alternate remittance systems in Ghana: a trade enabler or an organised fraud
Authors: Asmah Alexander , Atuilik Williams Abayaawien 
Published: November 2021

Purpose
Alternate remittance systems (ARS) are inherently not illegal; however, the nature of their activities has mostly been linked with money laundering and terrorist financing, which raises several questions as to why businesses in Ghana rely on these systems to conduct their cross-border trade. The purpose of this study is seeks to understand the nature of ARS in Ghana and analyse why business owners rely on them for their transactions.

Design/methodology/approach
Three companies were selected for the case study analysis. This research paper used a qualitative data analysis for the study. Interviews, direct participant observation and documentary review were the main techniques for data collection. The multiple sources of evidence helped to reduce the potential bias of the single method.

Findings
This paper found that some businesses using the system in Ghana can acquire unsecured loans at little or no interest cost, which provides a good source of funding to support business growth. Unlike other studies, this study proves that in some instances, ARS operators transact business with the clients they do not, particularly trust. Within the context of this study, this paper found evidence that supports money laundering, but the underlining crime is mostly tax evasion. The adoption of the system is an attempt to disguise the proceeds of the tax evasion crime and clean them through business operations.

Research limitations/implications
This analysis was based on the strain theory from the perspective of the clients. Future studies can focus attention on the ARS operators and understand their perspectives. Several other fraud theories could be used as a lens to understand the phenomena in Ghana and other jurisdictions.

Practical implications
The study throws more light on a “secret” or an underground banking system that operates in Ghana. It provides insights that can guide regulatory authorities in their policy implementation. The need for stricter enforcement of the law has also been highlighted.

Originality/value
To the best of the authors’ knowledge, this study is original, as it focuses on a sector that is highly secretive but has significant implications on the Ghanaian economy.
“Reporting the wrong to the right”: the mediated moderation model of whistleblowing education and the whistleblowing intentions
Authors: Aslam Muhammad Kashif , Akhtar Muhammad Saeed , Akhtar Muhammad Waheed , Asrar-ul-Haq Muhammad , Iqbal Jawad , Usman Muhammad 
Published: November 2021

PurposeThe purpose of this paper is to elucidate the social information processing theory, which is extended by the (1) effect of whistleblowing education on whistleblowing intentions, (2) simultaneous examination of the indirect relationship between whistleblowing education and whistleblowing intentions via moral identity and (3) relativism in influencing this mediation.Design/methodology/approachMulti-wave data collected at three internals from bank employees (n = 294) were analyzed to test the proposed model.FindingsResults of the study demonstrate that whistleblowing education favorably influences whistleblowing intentions directly as well as through moral identity. Relativism serves as the buffer in the indirect effects of whistleblowing education on whistleblowing intentions through moral identity attenuating these indirect effects in individuals with dominant relativism level.Originality/valueThis study strives to extend the whistleblowing education and whistleblowing intentions literature by unpacking a moral identity mechanism through which whistleblowing education kindles whistleblowing intention and relativism as boundary condition to attenuate such motivation.