bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACTActivating 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 SIGNIFICANCEWe 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

AbstractThe 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

AbstractCalculations 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

AbstractMotivationIn 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.ResultsViralMSA 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.AvailabilityViralMSA is freely available athttps://github.com/niemasd/ViralMSAas an open-source software project.Contacta1moshir@ucsd.edu
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

PurposeBased 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/approachA 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.FindingsResults 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/implicationsThrough 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 implicationsGiven 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/valueThis 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

PurposeThe 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/approachAn interpretive approach using data from 35 semi-structured interviews was adopted for this study. Data were transcribed and analyzed using the Gioia methodology.FindingsComparison 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 implicationsBy 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/valueHRM 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

PurposeFor 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/approachA narrative review was undertaken, but including some aspects of scoping review methodology.FindingsThirty-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/implicationsPhotovoice 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/valueThere 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

PurposeThis 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/approachWe 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.FindingsThe 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/implicationsAlthough 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 implicationsFrom 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/valueUnlike 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

PurposeElectrical 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/approachThe 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.FindingsThe 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/valueHardness 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

Abstract

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

AbstractThe 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.