bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted immuno-antiretroviral HIV therapeutic approach to provide dual protection and boosts cellular immunity: A proof-of-concept study
Authors: Mandal Subhra , Sunagawa Shawnalyn W. , Prathipati Pavan Kumar , Belshan Michael , Shibata Annemarie , Destache Christopher J.
Published: April 2020

Human immunodeficiency virus (HIV)-infected active and latent CCR5 expressing long-lived T-cells are the primary barrier to HIV/AIDS eradication. Broadly neutralizing antibodies and latency-reversing agents are the two most promising strategies emerging to achieve ‘functional cure’ against HIV infection. Antiretrovirals (ARVs) have shown to suppress plasma viral loads to non-detectable levels and above strategies have demonstrated a ‘functional cure’ against HIV infection is achievable. Both the above strategies are effective at inducing direct or immune-mediated cell death of latent HIV+ T-cells but have shown respective limitations. In this study, we designed a novel targeted ARVs-loaded nanoformulation that combines the CCR5 monoclonal antibody and antiretroviral drugs (ARV) as a dual protection strategy to promote HIV ‘functional cure’. The modified CCR5 monoclonal antibody (xfR5 mAb) surface-coated dolutegravir (DTG) and tenofovir alafenamide (TAF) loaded nanoformulation (xfR5-D+T NPs) were uniformly sized <250 nm, with 6.5 times enhanced antigen-binding affinity compared to naïve xfR5 mAb, and provided prolonged DTG and TAF intracellular retention (t1/2). The multivalent and sustained drug release properties of xfR5-D+T NPs enhance the protection efficiency against HIV by approximately 12, 3, and 5 times compared to naïve xfR5 mAb, D+T NP alone, and xfR5 NPs, respectively. Further, the nanoformulation demonstrated high binding-affinity to CCR5 expressing CD4+ cells, monocytes, and other HIV prone/latent T-cells by 25, 2, and 2 times, respectively. Further, the xfR5-D+T NPs during short-term pre-exposure prophylaxis induced a protective immunophenotype, i.e., boosted T-helper (Th), temporary memory (TM), and effector (E) sub-population. Moreover, treatment with xfR5-D+T NPs to HIV-infected T-cells induced a defensive/activated immunophenotype i.e., boosted naïve, Th, boosted central memory, TM, EM, E, and activated cytotoxic T-cells population. Therefore, this dual-action targeted mAb-ARV loaded nanoformulation could potentially become a multifactorial/multilayered solution to achieve a “functional cure.”
Schistosoma mansoniinfection reprograms the metabolic potential of the myeloid lineage in a mouse model of metabolic syndrome
Authors: Cortes-Selva Diana , Gibbs Lisa , Maschek J. Alan , Van Ry Tyler , Rajwa Bartek , Cox James E. , Amiel Eyal , Fairfax Keke C.
Published: April 2020

Despite evidence that helminths protect from metabolic disease, a major gap exists in understanding the underlying mechanism(s). Here we demonstrate that bone marrow derived macrophages (BMDM) fromS. mansoniinfected male ApoE-/-mice have dramatically increased mitochondrial respiration compared to those from uninfected mice. This change associates with increased glucose and palmitate shuttling into TCA cycle intermediates and decreased accumulation of cellular cholesterol esters. Moreover, systemic metabolic modulation by schistosomes is a function of biological sex, where infection protects ApoE-/-male, but not female, mice from obesity and glucose intolerance. Sex-dependence extends to myeloid cells, where reprogramming leads to opposite cholesterol phenotypes in BMDM from females and males. Finally, the metabolic reprogramming of male myeloid cells is transferrable via bone marrow transplantation to an uninfected host, indicating maintenance of reprogramming in the absence of sustained antigen exposure. This work reveals thatS. mansonisystemic reprograming of myeloid metabolism is sex-dependent.
Imprints of tumor mutation burden on chromosomes and relation to cancer risk in humans: A pan-cancer analysis
Authors: Li Xin , Thirumalai D.
Published: April 2020

Cancers, resulting in uncontrolled cell proliferation, are driven by accumulation of somatic mutations. Genome-wide sequencing has produced a catalogue of millions of somatic mutations, which contain the evolutionary history of the cancers. However, the connection between the mutation accumulation and disease development and risks is poorly understood. Here, we analyzed more than 1,200,000 mutations from 5,000 cancer patients with whole-exome sequencing, and discovered two novel signatures for 16 cancer types in The Cancer Genome Atlas (TCGA) database. A strong correlation between Tumor Mutation Burden (TMB) and the Patient Age at Diagnosis (PAD) is observed for cancers with low TMB (mean value less than 3 mutations per million base pairs) but is absent in cancers with high TMB. We also validate this finding using whole-genome sequencing data from more than 2,000 patients for 24 cancer types. Surprisingly, the differences in cancer risk between the sexes are also mainly driven by the disparity in mutation burden. The TMB variations, imprinted at the chromosome level, also reflect accumulation of mutation clusters within small chromosome segments in high TMB cancers. By analyzing the characteristics of mutations based on multi-region sequencing, we found that a combination of TMB and intratumor heterogeneity could a potential biomarker for predicting the patient survival and response to treatment.
Cadherin-6 mediates thrombosisin vivo
Authors: Bouck Emma G. , de la Fuente Maria , Zunica Elizabeth R. , Li Wei , Mumaw Michele M. , Nieman Marvin T.
Published: April 2020

Background

Platelet adhesion is the critical process mediating stable thrombus formation. Previous reports of cadherin-6 on human platelets have demonstrated its role in platelet aggregation and thrombus formation.

Objectives

We aimed to further characterize the importance of cadherin-6 in thrombosisin vivo.

Methods

Cadherin-6 platelet expression was evaluated by western blotting, flow cytometry and immunoprecipitation. Thrombosis was evaluated using the FeCl3and Rose Bengal carotid artery models in C57Bl6 mice treated with anti-cadherin-6 or IgG and wild-type orCdh6-/-mice. Platelet function was compared in wild type andCdh6-/-mice using tail-clip assays and aggregometry.

Results

Human platelet expression of cadherin-6 was confirmed at ~3,000 copies per platelet.Cdh6-/-mice or those treated with anti-Cadherin-6 antibody showed an increased time to occlusion in both thrombosis models. Cadherin-6 was not expressed on mouse platelets, and there were no differences in tail bleeding times or platelet aggregation in wild-type versusCdh6-/-mice.

Conclusions

Cadherin-6 plays an essential role in thrombosisin vivo. However, cadherin-6 is not expressed on murine platelets. These data are in contrast to human platelets, which express a functional cadherin-6/catenin complex. The essential, platelet-independent role for cadherin-6 in hemostasis may allow it to be an effective and safe therapeutic target.

Essentials

Cadherin-6 function in thrombus formation was investigated in vivo using two murine models of thrombosis.

Blocking or deleting cadherin-6 significantly delayed time to occlusion

Human platelets express cadherin-6, but murine platelets do not.
Temporal dynamics of ensemble statistics calculation using a neural network model
Authors: Sengupta Rakesh
Published: April 2020

Computing summary or ensemble statistics of a visual scene is often automatic and a hard necessity for stable perceptual life of a cognitive agent. Although computationally the process should be as simple as applying a filter as it were to a perceived scene, the issue of mechanism of summary statistics is complicated by the fact that we can seamlessly switch from summarizing to individuation while computing the ensemble averages across multiple reference frames. In the current work we have investigated the possibility of a neural network that can also switch between individuation and summarization. We have chosen a computational model previously used for enumeration/individuation (Sengupta et al, 2014) in order to show possibility of extracting summary statistics using two different measures from the network. The results also shed a light on possible temporal dynamics of ensemble perception.
Dendrites decrease the synaptic weight resolution necessary to implement linearly separable computations
Authors: Cazé Romain , Stimberg Marcel
Published: April 2020

In theory, neurons modelled as single layer perceptrons can implement all linearly separable computations. In practice, however, these computations may require arbitrarily precise synaptic weights. This is a strong constraint since both, biological neurons and their artificial counterparts, have to cope with limited precision. Here, we explore how the non-linear processing in dendrites helps overcoming this constraint. We start by finding a class of computations which requires increasing precision with the number of inputs in a perceptron and show that it can be implemented without this constraint in a neuron with sub-linear subunits. Then, we complement this analytical study by a simulation of a biophysical neuron model with two passive dendrites and a soma, and show that it can implement this computation. This works demonstrates a new role of dendrites in neural computation: by distributing the computation across independent subunits, the same computation can be performed more efficiently with less precise tuning of the synaptic weights. We hope that this works not only offers new insight into the importance of dendrites for biological neurons, but also paves the way for new, more efficient architectures of artificial neuromorphic chips.

Author Summary

In theory, we know how much neurons can compute, in practice, the number of possible synaptic weights values limits their computation capacity. Such a limitation holds true for artificial and synthetic neurons. We introduce here a computation where the required means evolve significantly with the number of inputs, this poses a problem as neurons receive multiple thousands of inputs. We study here how the neurons’ receptive element-called dendrites-can mitigate such a problem. We show that, without dendrites, the largest synaptic weight need to be multiple orders of magnitude larger than the smallest to implement the computation. Yet a neuron with dendrites implements the same computation with constant synaptic weights whatever the number of inputs. This study paves the way for the use of dendritic neurons in a new generation of artificial neural network and neuromorphic chips with a considerably better cost-benefit balance.
The microtubule-associated protein CLASP is translationally-regulated in light-dependent root apical meristem growth
Authors: Halat Laryssa , Gyte Katherine , Wasteneys Geoffrey
Published: April 2020

The ability for plant growth to be optimized, either in the light or dark, depends on the intricate balance between cell division and differentiation in specialized regions called meristems. WhenArabidopsis thalianaseedlings are grown in the dark, hypocotyl elongation is promoted, whereas root growth is greatly reduced as a result of changes in hormone transport and a reduction in meristematic cell proliferation. Previous work showed that the microtubule-associated protein CLASP sustains root apical meristem (RAM) size by influencing microtubule (MT) organization and by modulating the brassinosteroid (BR) signalling pathway. Here, we investigated whether CLASP is involved in light-dependent root growth promotion, since dark-grown seedlings have reduced RAM activity that is observed in theclasp-1null mutant. We showed that CLASP protein levels were greatly reduced in the root tips of dark-grown seedlings, which could be reversed by exposing plants to light. We confirmed that removing seedlings from the light led to a discernible shift in MT organization from bundled arrays, which are prominent in dividing cells, to transverse orientations typically observed in cells that have exited the meristem. BR receptors and auxin transporters, both of which are sustained by CLASP, were largely degraded in the dark. Interestingly, we found that despite the lack of protein,CLASPtranscript levels were higher in dark-grown root tips. Together, these findings uncover a mechanism that sustains meristem homeostasis through CLASP, and advances our understanding of how roots modulate their growth according to the amount of light and nutrients perceived by the plant.

One Sentence Summary

The microtubule-associated protein CLASP is regulated at the translational level when root meristem growth is inhibited in dark-grown plants.
Time-resolved transcriptome of barley anthers and meiocytes reveals robust and largely stable gene expression changes at meiosis entry
Authors: Barakate Abdellah , Orr Jamie , Schreiber Miriam , Colas Isabelle , Lewandowska Dominika , McCallum Nicola , Macaulay Malcolm , Morris Jenny , Arrieta Mikel , Hedley Pete E. , Ramsay Luke , Waugh Robbie
Published: April 2020

In flowering plants, successful germinal cell development and meiotic recombination depend upon a combination of environmental and genetic factors. To gain insights into this specialised reproductive development programme we used short- and long-read RNA-sequencing (RNA-seq) to study the temporal dynamics of transcript abundance in immuno-cytologically staged barley (Hordeum vulgare) anthers and meiocytes. We show that the most significant transcriptional changes occur at the transition from pre-meiosis to leptotene–zygotene, which is followed by largely stable transcript abundance throughout prophase I. Our analysis reveals that the developing anthers and meiocytes are enriched in long non-coding RNAs (lncRNAs) and that entry to meiosis is characterized by their robust and significant down regulation. Intriguingly, only 24% of a collection of putative meiotic gene orthologues showed differential transcript abundance in at least one stage or tissue comparison. Changes in the abundance of numerous transcription factors, representatives of the small RNA processing machinery, and post-translational modification pathways highlight the complexity of the regulatory networks involved. These developmental, time-resolved, and dynamic transcriptomes increase our understanding of anther and meiocyte development and will help guide future research.

One sentence summary

Analysis of RNA-seq data from meiotically staged barley anthers and meiocytes highlights the role of lncRNAs within a complex network of transcriptional and post-transcriptional regulation accompanied by a hiatus in differential gene expression during prophase I.

The author responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors (www.plantcell.org) is: Robbie Waugh (robbie.waugh@hutton.ac.uk)
Design an efficient multi-epitope peptide vaccine candidate against SARS-CoV-2: An in silico analysis
Authors: Yazdani Zahra , Rafiei Alireza , Yazdani Mohammadreza , Valadan Reza
Published: April 2020

Background

To date, no specific vaccine or drug has been proven to be effective for SARS-CoV-2 infection. Therefore, we implemented immunoinformatics approach to design an efficient multi-epitopes vaccine against SARS-CoV-2.

Results

The designed vaccine construct has several immunodominant epitopes from structural proteins of Spike, Nucleocapsid, Membrane and Envelope. These peptides promote cellular and humoral immunity and Interferon gamma responses. In addition, these epitopes have antigenicity ability and no allergenicity probability. To enhance the vaccine immunogenicity, we used three potent adjuvants; Flagellin, a driven peptide from high mobility group box 1 as HP-91 and human beta defensin 3 protein. The physicochemical and immunological properties of the vaccine structure were evaluated. Tertiary structure of the vaccine protein was predicted and refined by I-Tasser and galaxi refine and validated using Rampage and ERRAT. Results of Ellipro showed 242 residues from vaccine might be conformational B cell epitopes. Docking of vaccine with Toll-Like Receptors 3, 5 and 8 proved an appropriate interaction between the vaccine and receptor proteins. In silico cloning demonstrated that the vaccine can be efficiently expressed inEscherichia coli.

Conclusions

The designed multi epitope vaccine is potentially antigenic in nature and has the ability to induce humoral and cellular immune responses against SARS-CoV-2. This vaccine can interact appropriately with the TLR3, 5, and 8. Also, this vaccine has high quality structure and suitable characteristics such as high stability and potential for expression inEscherichia coli.
Combined Proteomic and Genetic Interaction Mapping Reveals New RAS Effector Pathways and Susceptibilities
Authors: Kelly Marcus R. , Kostyrko Kaja , Han Kyuho , Mooney Nancie , Jeng Edwin E. , Abbott Keene L. , Gwinn Dana M. , Sweet-Cordero E. Alejandro , Bassik Michael C. , Jackson Peter K.
Published: April 2020

Activating mutations in RAS GTPases drive one fifth of cancers, but poor understanding of many RAS effectors and regulators, and of the roles of their different paralogs, continues to impede drug development. We developed a multi-stage discovery and screening process to understand RAS function and identify RAS-related susceptibilities in lung adenocarcinoma. Using affinity purification mass spectrometry (AP/MS), we generated a protein-protein interaction map of the RAS pathway containing thousands of interactions. From this network we constructed a CRISPR dual knockout library targeting 119 RAS-related genes that we screened for genetic interactions (GIs). We found important new effectors of RAS-driven cellular functions, RADIL and the GEF RIN1, and over 250 synthetic lethal GIs, including a potentKRAS-dependent interaction betweenRAP1GDS1andRHOA. Many GIs link specific paralogs within and between gene families. These findings illustrate the power of the multiomic approach to identify synthetic lethal combinations for hitherto undruggable cancers.

STATEMENT OF SIGNIFICANCE

We present a thorough survey of protein-protein and genetic interactions in the Ras pathway. These interactions suggested new discoveries that we validate here, and demonstrate important new paralog specificities and redundancies. By comparing synthetic lethal interactions acrossKRAS-dependent and -independent tumors, we identify new combination therapy targets against Ras-driven cancers.
Structure-guided point mutations on FusionRed produce a brighter red fluorescent protein
Authors: Mukherjee Srijit , Hung Sheng-Ting , Douglas Nancy , Manna Premashis , Thomas Connor , Ekrem Annika , Palmer Amy E. , Jimenez Ralph
Published: April 2020

The development of fluorescent proteins (FPs) has revolutionized biological imaging. FusionRed, a monomeric red FP (RFP), is known for its low cytotoxicity and appropriate localization of target fusion proteins in mammalian cells but is limited in application by low fluorescence brightness. We report a brighter variant of FusionRed, FusionRed-MQV, which exhibits an extended fluorescence lifetime (2.8 ns), enhanced quantum yield (0.53), higher extinction coefficient (~140,000 M−1cm−1), increased radiative rate constant and reduced non-radiative rate constant with respect to its precursor. The properties of FusionRed-MQV derive from three mutations - M42Q, C159V and the previously identified L175M. A structure-guided approach was used to identify and mutate candidate residues around the phenol and the acylimine ends of the chromophore. The C159V mutation was identified via lifetime-based flow cytometry screening of a library in which multiple residues adjacent to the phenol end of the chromophore were mutated. The M42Q mutation is located near the acylimine end of the chromophore and was discovered using site-directed mutagenesis guided by x-ray crystal structures. FusionRed-MQV exhibits 3.4-fold higher molecular brightness and a 5-fold increase in the cellular brightness in HeLa cells (based on FACS) compared to FusionRed. It also retains the low cytotoxicity and high-fidelity localization of FusionRed, as demonstrated through assays in mammalian cells.
Ligand Gaussian accelerated molecular dynamics (LiGaMD): Characterization of ligand binding thermodynamics and kinetics
Authors: Miao Yinglong , Bhattarai Apurba , Wang Jinan
Published: April 2020

Calculations of ligand binding free energies and kinetic rates are important for drug design. However, such tasks have proven challenging in computational chemistry and biophysics. To address this challenge, we have developed a new computational method “LiGaMD”, which selectively boosts the ligand non-bonded interaction potential energy based on the Gaussian accelerated molecular dynamics (GaMD) enhanced sampling technique. Another boost potential could be applied to the remaining potential energy of the entire system in a dual-boost algorithm (LiGaMD_Dual) to facilitate ligand binding. LiGaMD has been demonstrated on host-guest and protein-ligand binding model systems. Repetitive guest binding and unbinding in the β-cyclodextrin host were observed in hundreds-of-nanosecond LiGaMD simulations. The calculated binding free energies of guest molecules with sufficient sampling agreed excellently with experimental data (< 1.0 kcal/mol error). In comparison with previous microsecond-timescale conventional molecular dynamics simulations, accelerations of ligand kinetic rate constants in LiGaMD simulations were properly estimated using Kramers’ rate theory. Furthermore, LiGaMD allowed us to capture repetitive dissociation and binding of the benzamidine inhibitor in trypsin within 1 μs simulations. The calculated ligand binding free energy and kinetic rate constants compared well with the experimental data. In summary, LiGaMD provides a promising approach for characterizing ligand binding thermodynamics and kinetics simultaneously, which is expected to facilitate computer-aided drug design.
ViralMSA: Massively scalable reference-guided multiple sequence alignment of viral genomes
Authors: Moshiri Niema
Published: April 2020

Motivation

In molecular epidemiology, the identification of clusters of transmissions typically requires the alignment of viral genomic sequence data. However, existing methods of multiple sequence alignment scale poorly with respect to the number of sequences.

Results

ViralMSA is a user-friendly reference-guided multiple sequence alignment tool that leverages the algorithmic techniques of read mappers to enable the multiple sequence alignment of ultra-large viral genome datasets. It scales linearly with the number of sequences, and it is able to align tens of thousands of full viral genomes in seconds.

Availability

ViralMSA is freely available athttps://github.com/niemasd/ViralMSAas an open-source software project.

Contact

a1moshir@ucsd.edu
2,6-Diphenyl-3-(prop-2-en-1-yl)piperidin-4-one
Authors: Manjula V. , Venkateswaramoorthi R. , Dharmaraja J. , Selvanayagam S.
Published: April 2020

In the title compound, C20H21NO, the dihedral angle between the phenyl ring is 47.5 (1)° and the piperidine ring adopts a chair conformation. In the crystal, molecules are linked by C—H...π interactions into dimers with the molecules related by twofold symmetry.
Cabin posture adjustment method based on redundant constrained parallel mechanism
Authors: Chu Wenmin , Huang Xiang , Li Shuanggao
Published: April 2020

Purpose

Posture adjustment plays an important role in spacecraft manufacturing. The traditional posture adjustment method, which has a large workload and is difficult to guarantee the quality of posture adjustment, cannot meet the requirements of modern spacecraft manufacturing. This paper aims to optimize the trajectory of posture adjustment, reduce the internal force of the posture adjustment mechanism and improve the accuracy of the system.

Design/methodology/approach

First, the measuring point is measured by a laser tracker and the position and posture of the cabin is solved. Then, Newton–Euler method is used to construct the dynamic model of the posture adjustment system (PAS) without internal force. Finally, the adjustment time is optimized based on Fibonacci search method and the trajectory of the cabin is fitted by the fifth order polynomial.

Findings

The simulation results show that, compared with the other trajectory planning methods, this method can effectively avoid the internal force of posture adjustment caused by redundant driving, and the trajectory of velocity and acceleration obtained are continuous, meeting the engineering constraints.

Originality/value

In this paper, a dynamic model of PAS without internal force is constructed. The trajectory planning of posture adjustment based on this model can improve the quality of cabin assembly.
Linking career adaptability to supervisor-rated task performance: a serial mediation model
Authors: Haynie Jeffrey , Flynn C. Brian , Herda David
Published: April 2020

Purpose

Based on a combination of career construction theory (CCT) and conservation of resources (COR) theory, this study proposes and examines a serial mediation model connecting proactive personality with supervisor-rated task performance sequentially through career adaptability and job engagement.

Design/methodology/approach

A sample of 177 supervisor–subordinate dyads in the United States participated in the multisource survey, and structural equation modeling was used to test the hypotheses. The proposed indirect effects were evaluated using a bootstrap procedure.

Findings

Results indicated that career adaptability mediated the relationship between proactive personality and job engagement, job engagement mediated the relationship between career adaptability and supervisor-rated task performance and career adaptability and job engagement sequentially mediated the relationship between proactive personality and supervisor-rated task performance.

Research limitations/implications

Through an examination of the nomological network pertaining to career adaptability, the results provide strong evidence in support of integrating CCT with COR theory in this research stream. Future studies should continue to expand upon the model presented here by considering potential moderators that might influence certain paths within this relationship network and use longitudinal designs to allow for stronger causal inferences.

Practical implications

Given the central role proactive personality plays in career construction and job engagement, organizations should encourage workers to be more proactive while on the job. This may help engender career adaptability and work engagement among employees – ultimately contributing to organizational success.

Originality/value

This study responds to calls linking career adaptability to supervisory ratings of work performance. In doing so, it advances the literatures on proactive personality and career adaptability by highlighting the importance of considering the tenets of both CCT and COR theory.
Sustainable HRM: toward addressing diverse employee roles
Authors: Podgorodnichenko Nataliya , Akmal Adeel , Edgar Fiona , Everett Andrè M.
Published: April 2020

Purpose

The purpose of this empirical study is to develop an understanding of how human resource (HR) managers employed by organizations with an explicit sustainability agenda view employees as stakeholders, and to explore how such views are operationalized in HR policies and practices.

Design/methodology/approach

An interpretive approach using data from 35 semi-structured interviews was adopted for this study. Data were transcribed and analyzed using the Gioia methodology.

Findings

Comparison of approaches to sustainable human resource management (HRM) revealed three distinctive conceptualizations of employees with respect to the sustainability agenda – employees as a driving force for sustainability, employees as consumers of HR practices and employees as members of a community. Strong levels of integration between the HRM and sustainability agendas were only evidenced in those organizations where an attempt had been made to address all three roles simultaneously. Findings suggest that engagement with a sustainability agenda widens the remit of the HRM function, underscoring the importance of employees' roles as consumers of HR practices and as members of wider communities.

Practical implications

By addressing the integration of HRM with a sustainability agenda, this article helps practitioners recognize diversity among employees' roles and the varying associated needs. Examples of policy and practice initiatives that effectively address these needs are provided.

Originality/value

HRM has been widely criticized for overemphasizing shareholder value, thereby lacking in attention to the needs of other stakeholders, including employees. Findings from this study suggest the holistic approach advocated by a sustainability agenda can effectively quell these concerns.
Gender research in hospitality and tourism management: time to change the guard
Authors: Mooney Shelagh K.
Published: April 2020

Purpose

The purpose of this paper is to explain the problem with how gender is positioned in hospitality and tourism management studies. It recommends critical theories to investigate how gender is researched in the sector’s academic and institutional systems.

Design/methodology/approach

The conceptual study explains contemporary gender theories and gives examples of relevant hospitality and tourism management studies. A four point critical agenda for researching gender is proposed and justified.

Findings

The study highlights how the focus on “female leadership” as different from the male norm and the use of traditional theoretical framings reinforce stereotypes about the primacy of women’s domestic commitments to their detriment.

Research limitations/implications

A limitation of this academy focussed study is that it has not recommended specific initiatives to combat specific issues of gender discrimination in hospitality and tourism employment. A further limitation is that the primary focus was on critical management theory to explain heteronormative based gender discrimination. It did not discuss queer theory.

Practical implications

In addition, a new research agenda, steps are proposed to change the masculine culture. Hospitality and tourism universities and research institutions should review men’s/women’s/gender diverse representation at leadership levels. Critical gender research approaches may also be fostered by sectorial conference streams and journal special issues and university graduate research students should be taught to design such studies.

Social implications

The use of contemporary approaches in gender studies will enable researchers to propose more targeted equality and diversity management actions for industry. They will also assist educators to better design curricula that protect and promote the interests of women studying a hospitality, tourism or events degree and those who identify as gender diverse.

Originality/value

The paper challenges the masculine status quo in hospitality and tourism management gender studies, arguing that adherence to traditional orthodoxies has stifled the development of critical paradigms and methodologies. Its key contribution is to reveal the advantages that critical gender theorising can bring to further the aim of gender equality by showing practical applications.
The evolution of community-based rehabilitation (CBR) programmes: a call for mixed evaluation methodologies
Authors: Shumba Tonderai Washington , Haufiku Desderius , Mitonga Kabwebwe Honoré
Published: April 2020

Purpose

For the past four decades, there is no evidence of a consensus on the suitable community-based rehabilitation (CBR) evaluation methodologies. To this end, the purpose of this study is to provide a narrative review on CBR evaluations and the potential of photovoice method when used alone and when used in combination with quality of life assessment tools as CBR evaluation methodologies.

Design/methodology/approach

A narrative review was undertaken, but including some aspects of scoping review methodology.

Findings

Thirty-three full-text articles were included for review. Three key findings were an overview of the evolution of CBR evaluation; the use of photovoice method in CBR evaluation and the use of photovoice method in combination with quality of life assessment tools in CBR evaluation.

Research limitations/implications

Photovoice methodology was found to be participatory in nature and as has the potential to elicit the experiences of persons with disabilities. However, photovoice falls short of measuring the quality of life of persons with disabilities, thus will need to be collaborated with another assessment tool. A combination of photovoice and World Health Organization Quality of Life (WHOQOL)-BREF and WHOQOL-Dis assessment has a potential to give an adequate representation of the voices of persons with disabilities and their quality of life.

Originality/value

There is need for changes in CBR evaluation methodologies in response to the evolution of disability models from medical model to human rights model. Thus CBR evaluation methodologies should embrace the diversity among persons with disabilities in interpreting life experiences and quality of life.
The effect of perceived legitimacy on new venture growth in Japan: a moderated mediation approach
Authors: Kawai Norifumi , Xheneti Mirela , Kazumi Tomoyo
Published: April 2020

Purpose

This article seeks to theorize and empirically examine the conditional mechanisms through which entrepreneurial legitimacy determines the success or failure of new ventures by building upon Zimmerman and Zeitz's (2002) causal process model of legitimacy.

Design/methodology/approach

We gathered cross-sectional data from 266 Japanese new venture owners running their businesses across a variety of sectors and empirically examined whether, how and when legitimacy positively affects new ventures' performance by employing the SPSS PROCESS macro for moderated mediation analysis.

Findings

The results indicate that rich access to a pool of valuable resources fully mediates the positive effects of legitimacy on new venture growth. Furthermore, this study offers robust empirical evidence that prior entrepreneurial experience and competitive intensity as the internal and external contingency factors significantly moderate the indirect effect of legitimacy on new venture growth through resource accessibility.

Research limitations/implications

Although our analysis provides clear support for the view that important resources for new venture performance are gained through legitimacy, it does not offer precise clarifications for the type and sources of legitimacy and for the strategies that could be deployed to achieve legitimacy. Future studies should clearly distinguish tangible assets (e.g. financial resources) from intangible assets (e.g. tacit knowledge, networks and reputation) in terms of resource accessibility. Therefore, it should be worth scrutinizing the multiple dimensions of resources as potential mediators of the legitimacy-new venture growth relationship in greater depth.

Practical implications

From a policy perspective, this study suggests that a special emphasis needs to be placed on designing and carrying out policies aimed at increasing the visibility and credibility of entrepreneurship as a positive career path since public acceptance of entrepreneurship is essential to new venture growth. Furthermore, it is logical to conclude that achieving greater legitimacy is a pivotal strategic tool not only to overcome resource barriers but also to maximize a probability of survival, specifically for those entrepreneurs without prior experience and those operating in a fiercely competitive market environment.

Originality/value

Unlike previous studies that have mostly presented the direct effect of entrepreneurial legitimacy on venture outcomes (Capelleraset al., 2019; Kibler and Kautonen, 2016; Pindado and Sánchez, 2017), our research empirically identified the potential complexities inherent in this relationship by performing a conditional indirect effect analysis.
Investigation on effect of process parameter on surface integrity during electrical discharge machining of NiTi 60
Authors: Gaikwad Mahendra Uttam , Krishnamoorthy A. , Jatti Vijaykumar S.
Published: April 2020

Purpose

Electrical discharge machining (EDM) of hard materials like NiTi 60 alloys is important as it finds application in different sectors of engineering such as automobile, aircraft, biomedical, oil industries, etc.

Design/methodology/approach

The first target of this investigation is to determine the effect of process parameters such as current, voltage, pulse on time and pulse off time on the material removal rate (MRR), surface roughness (SR) and white layer formation (WLT) for NiTi 60 smart material alloy. The secondary aim is to identify the presence of surface integrity parameters such as cracks, WLT, microvoids, globules and debris formation by using the scanning electron microscopy technique and with the use of ImageJ software for die sink EDM machining of NiTi 60 alloy.

Findings

The results reveal that current is significant for MRR, voltage and current influence SR, and for WLT, voltage is a significant factor. The experimentation study also shows the generation of oxide and carbide layers on the machined surface, which were evident with the use of the X-ray diffraction technique. The presence of these oxide and carbide layers causes to form WLT on the machined surface and thereby increases the hardness of the machined surface.

Originality/value

Hardness test was performed with Vickers hardness tester, which gives evidence for the increase in hardness of machined surface due to the generation of WLT.
Rapid and repeated divergence of animal chemical signals in an island introduction experiment
Authors: Donihue Colin M. , Herrel Anthony , Martín José , Foufopoulos Johannes , Pafilis Panayiotis , Baeckens Simon
Published: April 2020

Studies of animal communication have documented myriad rapid, context‐dependent changes in visual and acoustic signal design. In contrast, relatively little is known about the capacity of vertebrate chemical signals to rapidly respond, either plastically or deterministically, to changes in context.

Four years following an experimental introduction of lizards to replicate experimental islets, we aimed to determine if chemical signal design of the experimental populations differed from that of the source population.

In 2014, we translocated Podarcis erhardii lizards from a large, predator‐rich island to each of five replicate predator‐free islets. Mean population densities increased fivefold over the following 4 years and bite scars suggest significantly more intraspecific fighting among these experimental populations. In 2018, we analysed the chemical signal design of males in each of the experimental populations and compared it to the chemical signals of the source population.

We found that males consistently presented a significantly more complex chemical signal compared to the source population. Moreover, their chemical signals were marked by high proportions of octadecanoic acid, oleic acid and α‐tocopherol, the three compounds that are known to be associated with lizard territoriality and mate choice.

Our island introduction experiment thus suggests that the chemical signal design of animals can shift rapidly and predictably in novel ecological contexts.
The adoption of cattle pastoralism in the Arabian Peninsula: A reappraisal
Authors: Makarewicz Cheryl A.
Published: April 2020

The translocation of livestock into the Arabian Peninsula was underway by the sixth millennium BC. It remains unclear, however, whether nascent pastoralism in Arabia focused on specialised cattle herding, intensive caprine husbandry, or more extensive forms of sheep, goat and cattle management. Here, the role of Bos in Neolithic animal exploitation systems in the Arabian Peninsula is re‐examined in the context of fisher‐hunter‐gatherer groups inhabiting the coasts of the Arabian Gulf, agro‐pastoralist settlements located in the Jordanian highlands, and hunter‐herder communities in adjacent Jordanian steppe (badia). By the late sixth millennium BC, cattle from southern Mesopotamia were imported to the Arabian littoral via Ubaid exchange networks but remained a relatively unimportant part of local hunter‐gatherer‐herder subsistence for at least a millennium. New zooarchaeological evidence indicating cattle herding in the Jordanian highlands by the late eighth millennium BC suggests a southern transmission route originating out of Late Pre‐Pottery Neolithic B settlements and the subsequent spread of cattle along the Sarawat mountains into the interior or down the relatively arid Red Sea coast via land or boat. Cattle eventually played a central role in the symbolic and ritual lives of herders in southern Arabia, but the use of the term ‘cattle pastoralism’ to describe early Neolithic subsistence systems in the region is premature.
End‐expiratory lung volume assessment using helium and carbon dioxide in an experimental model of pediatric capnoperitoneum
Authors: Karlsson Jacob , Fodor Gergely H. , dos Santos Rocha Andre , Lin Na , Habre Walid , Wallin Mats , Hallbäck Magnus , Peták Ferenc , Lönnqvist Per‐Arne
Published: April 2020

Background

Capnoperitoneum during laparoscopy leads to cranial shift of the diaphragm, loss in lung volume, and risk of impaired gas exchange. Infants are susceptible to these changes and bedside assessment of lung volume during laparoscopy might assist with optimizing the ventilation. Thus, the primary aim was to investigate the monitoring value of a continuous end‐expiratory lung volume (EELV) assessment method based on CO2 dynamics (

) in a pediatric capnoperitoneum model by evaluating the correlation and trending ability against helium washout (EELVHe).

Methods

Intra‐abdominal pressure (IAP) was randomly varied between 0, 6, and 12 mm Hg with CO2 insufflation, while positive end‐expiratory pressure (PEEP) levels of 3, 6, and 9 cm H2O were randomly applied in eight anesthetized and mechanically ventilated chinchilla rabbits. Concomitant

and EELVHe and lung clearance index (LCI) were obtained under each experimental condition.

Results

Significant correlations were found between

and EELVHe before capnoperitoneum (r = .85, P < .001), although increased IAP distorted this relationship. The negative influence of IAP was counteracted by the application of PEEP 9, which restored the correlation between

and EELVHe and resulted in 100% concordance rate between the methods regarding changes in lung volume. EELVHe and LCI showed a curvilinear relationship, and an EELVHe of approximately 20 mL kg−1, determined with a receiver operating characteristic curve, was associated with near‐normal LCI values.

Conclusion

In this animal model of pediatric capnoperitoneum, reliable assessment of changes in EELV based on

requires an open lung strategy, defined as EELV above approximately 20 mL kg−1.
Non‐surgical interdisciplinary management for an adult patient with a Class III malocclusion
Authors: Low CYS , Ong DC‐V , Freer E
Published: April 2020

Non‐surgical camouflage orthodontic treatment can be effective for the management of carefully selected patients with mild to moderate Class III malocclusion. This case report demonstrates how a synergistic combination of camouflage orthodontic treatment and appropriate adjunctive restorative procedures can provide a pleasing treatment outcome for a patient with a significant skeletal Class III malocclusion and diminutive maxillary lateral incisors.
The association of pre‐operative anaemia with morbidity and mortality after emergency laparotomy
Authors: Boyd‐Carson H. , Shah A. , Sugavanam A. , Reid J. , Stanworth S. J. , Oliver C. M.
Published: April 2020

Pre‐operative anaemia is associated with poor outcomes after elective surgery but its relationship with outcomes after emergency surgery is unclear. We analysed National Emergency Laparotomy Audit data from 1 December 2013 to 30 November 2017, excluding laparotomy for haemorrhage. Anaemia was classified as ‘mild’ 129–110 g.l−1; ‘moderate’ 109–80 g.l−1; or ‘severe’ ≤ 79 g.l−1. The primary outcome was 90‐day mortality. Secondary outcomes were 30‐day mortality, return to theatre and postoperative hospital stay. The primary outcome was available for 86,763 patients, of whom 45,306 (52%) were anaemic. There were 12,667 (15%) deaths at 90 postoperative days and 9246 (11%) deaths at 30 postoperative days. Anaemia was associated with increased 90‐day and 30‐day mortality, odds ratio (95%CI): mild, 1.15 (1.09–1.21); moderate, 1.44 (1.36–1.52); and severe, 1.42 (1.24–1.63), p < 0.001 for all; mild, 1.07 (1.00–1.12), p = 0.030; moderate, 1.30 (1.21–1.38), p < 0.001; and severe, 1.22 (1.05–1.43), p = 0.010, respectively. All categories of anaemia were associated with prolonged hospital stay, adjusted coefficient (95%CI): mild, 1.31 (1.01–1.62); moderate, 3.41 (3.04–3.77); severe, 2.80 (1.83–3.77), p < 0.001 for all. Moderate and severe anaemia were associated with increased risk of return to the operating theatre, odds ratio (95%CI): moderate 1.13 (1.06–1.21), p < 0.001; and severe 1.23 (1.06–1.43), p = 0.006. Pre‐operative anaemia is common in patients undergoing emergency laparotomy and is associated with increased postoperative mortality and morbidity.
The Wee1 kinase inhibitor MK1775 suppresses cell growth, attenuates stemness and synergises with bortezomib in multiple myeloma
Authors: Liang Long , He Yanjuan , Wang Haiqin , Zhou Hui , Xiao Ling , Ye Mao , Kuang Yijin , Luo Saiqun , Zuo Yuna , Feng Peifu , Yang Chaoying , Cao Wenjie , Liu Taohua , Roy Mridul , Xiao Xiaojuan , Liu Jing
Published: April 2020

Multiple myeloma stem‐like cells (MMSCs) are responsible for initiation and relapse, though novel treatment paradigms that effectively eradicate MMSCs are yet to be developed. Selective inhibition of the cell cycle regulatory kinase Wee1 by MK1775 is being explored as a potential anti‐cancer therapeutic. We report that higher expression of Wee1 is correlated with poor survival in multiple myeloma (MM). The MM models and patient‐derived CD138+ plasma cells are particularly sensitive to the growth‐inhibitory effects of the Wee1 inhibitor MK1775. MK1775 induces Mus81‐Eme1 endonuclease‐mediated DNA damage in S‐phase cell cycle that results in a blockade of replication and then apoptosis. Furthermore, MK1775 strongly suppresses the features of stemness in vitro, in vivo and in primary CD138+ cells by decreasing ALDH1+ cell fraction and the expression of ALDH1. In addition, co‐treatment of MK1775 with bortezomib is synergistic in vitro and in vivo. Bortezomib, although it enhances ALDH1+ cells, when combined with MK1775 abrogates this stimulatory effect on stemness. Considering MM as an invariably incurable malignancy due to the presence of heterogenic myeloma stem‐like cells, our study presents inhibition of Wee1 as a promising targeted therapy for MM and provides a compelling rationale to further investigate the activity of MK1775 against myeloma in clinical settings.