bluuebunny/crossref_metadata_2025_split huggingface dataset:
Benchmarking ensemble docking methods as a scientific outreach project
Authors: Gan Jessie L. , Kumar Dhruv , Chen Cynthia , Taylor Bryn C. , Jagger Benjamin R. , Amaro Rommie E. , Lee Christopher T. 
Published: October 2020

ABSTRACTThe discovery of new drugs is a time consuming and expensive process. Methods such as virtual screening, which can filter out ineffective compounds from drug libraries prior to expensive experimental study, have become popular research topics. As the computational drug discovery community has grown, in order to benchmark the various advances in methodology, organizations such as the Drug Design Data Resource have begun hosting blinded grand challenges seeking to identify the best methods for ligand pose-prediction, ligand affinity ranking, and free energy calculations. Such open challenges offer a unique opportunity for researchers to partner with junior students (e.g., high school and undergraduate) to validate basic yet fundamental hypotheses considered to be uninteresting to domain experts. Here, we, a group of high school-aged students and their mentors, present the results of our participation in Grand Challenge 4 where we predicted ligand affinity rankings for the Cathepsin S protease, an important protein target for autoimmune diseases. To investigate the effect of incorporating receptor dynamics on ligand affinity rankings, we employed the Relaxed Complex Scheme, a molecular docking method paired with molecular dynamics-generated receptor conformations. We found that CatS is a difficult target for molecular docking and we explore some advanced methods such as distance-restrained docking to try to improve the correlation with experiments. This project has exemplified the capabilities of high school students when supported with a rigorous curriculum, and demonstrates the value of community-driven competitions for beginners in computational drug discovery.
Application of EGCG modified EDC/NHS cross-linked extracellular matrix to promote macrophage adhesion
Authors: Chu Chenyu , Rung Shengan , Yang Renli , Man Yi , Qu Yili 
Published: October 2020

AbstractThough chemically cross-linked by EDC/NHS endows collagen membrane with promising mechanical properties, it is not conducive to modulation of foreign body reaction (FBR) after implantation or guidance of osteogenesis. In our previous research, we have found that macrophages have a strong regulatory effect on tissue and bone regeneration during FBR, and EGCG modified membranes could adjust the recruitment and phenotypes of macrophages. Accordingly, we develop the EGCG-EDC/NHS membranes, prepared with physically immersion, while the surface morphology of the membrane was observed by SEM, the biological activity of collagen was determined by FTIR, the activity and adhesion of cell culturein vitro, angiogenesis and monocyte/macrophage recruitment after subcutaneous implantation, etc. are characterized. It could be concluded that EGCG-EDC/NHS collagen membrane is hopeful to be used in implant dentistry for it not only retains the advantages of the collagen membrane itself, but also improves cell viability, adhesion and vascularization tendency. However, the mechanism that lies in the regenerative advantages of such membrane needs further exploration, but it is certain that the differences in surface morphology can have a significant impact on the reaction between the host and the implant, not to mention macrophage in bone regeneration.
The Endoplasmic Reticulum Proteostasis Regulator ATF6 is Essential for Human Cone Photoreceptor Development
Authors: Kroeger Heike , Grandjean Julia M. D. , Chiang Wei-Chieh Jerry , Bindels Daphne , Mastey Rebecca , Okalova Jennifer , Nguyen Amanda , Powers Evan T. , Kelly Jeffery W. , Grimsey Neil J. , Michaelides Michel , Carroll Joseph , Wiseman R. Luke , Lin Jonathan H. 
Published: October 2020

AbstractDysregulation of the endoplasmic reticulum (ER) Unfolded Protein Response (UPR) is implicated in the pathology of many human diseases associated with ER stress. Inactivating genetic variants in the UPR regulatorActivating Transcription Factor 6 (ATF6)cause severe congenital heritable vision loss in patients by an unknown pathomechanism. To investigate this, we generated retinal organoids from patient iPSCs carryingATF6disease-causing variants andATF6null hESCs generated by CRISPR. Interestingly, we found that cone photoreceptor cells inATF6mutant retinal organoids lacked inner and outer segments concomitant with absence of cone phototransduction gene expression; while rod photoreceptors developed normally. Adaptive optics retinal imaging of patients with disease-causing variants inATF6also showed absence of cone inner/outer segment structures but preserved rod structures, mirroring the phenotypes observed in our retinal organoids. These results reveal thatATF6is essential for the formation of human cone photoreceptors, and associated absence of cone phototransduction components explains the severe visual impairment in patients withATF6-associated retinopathy. Moreover, we show that a selective small molecule ATF6 activator compound restores the transcriptional activity ofATF6disease-causing variants and stimulates the growth of cone photoreceptors in patient retinal organoids, demonstrating that pharmacologic targeting of ATF6 signaling is a therapeutic strategy that needs to be further explored for blinding retinal diseases.
The timing of human adaptation from Neanderthal introgression
Authors: Yair Sivan , Lee Kristin M. , Coop Graham 
Published: October 2020

AbstractAdmixture has the potential to facilitate adaptation by providing alleles that are immediately adaptive in a new environment or by simply increasing the long term reservoir of genetic diversity for future adaptation. A growing number of cases of adaptive introgression are being identified in species across the tree of life, however the timing of selection, and therefore the importance of the different evolutionary roles of admixture, is typically unknown. Here, we investigate the spatio-temporal history of selection favoring Neanderthal-introgressed alleles in modern human populations. Using both ancient and present-day samples of modern humans, we integrate the known demographic history of populations, namely population divergence and migration, with tests for selection. We model how a sweep placed along different branches of an admixture graph acts to modify the variance and covariance in neutral allele frequencies among populations at linked loci. Using a method based on this model of allele frequencies, we study previously identified cases of Neanderthal adaptive introgression. From these, we identify cases in which Neanderthal introgressed alleles were quickly beneficial and other cases in which they persisted at low frequency for some time. For some of the alleles that persisted at low frequency, we show that selection likely independently favored them later on in geographically separated populations. Our work highlights how admixture with ancient hominins has contributed to modern human adaptation and contextualizes observed levels of Neanderthal ancestry in present-day and ancient samples.
Discovery of tREP-18, a novel class oftRNA encoded peptide with potent leishmanicidal activity
Authors: Chakrabarti Amrita , Kaushik Monika , Khan Juveria , Soota Deepanshu , Kalairasan P , Saini Sunil , Manvati Siddharth , Singhal Jhalak , Ranganathan Anand , Pati Soumya , Dhar Pawan K. , Singh Shailja 
Published: October 2020

AbstractIn the post genomic era, tRNA-derived fragments have emerged as a new class of non-coding gene regulators, those play crucial roles both at the transcriptional and translational levels, in different cellular biogenesis. However, none of the studies has ever asked whether tRNAs can also be translated into peptides with any biological significance. Thus, we present a novel hypothesis which suggested that; design and synthesis of tRNA-derived peptides from prokaryotic genome can be exploited for developing unique chemotherapeutics against neglected tropical diseases, like Visceral leishmaniasis (VL) and its aggressive form known as post kalazar dermal leishmaniasis (PKDL). To achieve this aim, we have used a novel system biology-based strategy, which involved; i)mining of unique tRNAs from E. coli genome and their translation into peptide in silico, ii)designing of theoretical 3D models to evaluate their stability, iii)prediction of their biological activity by screening against anti-parasitic database to filter the lead peptide. Based on this strategy, a unique tRNA-derived peptide (tREP-18) was selected, chemically synthesized, and usedin vitrofor elucidating its therapeutic significance againstL. donovani, a causative agent of VL and PKDL. Our findings demonstrated that,tREP-18can impose high level toxicity toL. donovanipromastigotes, by disrupting the ultrastructural cellular architect, destabilizing the mitochondrial membrane potential (ΔΨm), thus leading to drastic reduction in cell viability and proliferation. It also imparted high level of toxicity to BS12 a clinical isolate of PKDL. Conceivably, we for the first time reports a novel tRNA-derived peptide “tREP18” with excellent anti-leishmanial property, which can be further utilized for developing it as antileishmanial drug.One Sentence SummaryHere we report a novel first-in-class tRNA encoded peptide and its super anti-leishmanial characteristics.
CEP78 functions downstream of CEP350 to control biogenesis of primary cilia by negatively regulating CP110 levels
Authors: Gonçalves André Brás , Hasselbalch Sarah Kirstine , Joensen Beinta Biskopstø , Patzke Sebastian , Martens Pernille , Ohlsen Signe Krogh , Quinodoz Mathieu , Nikopoulos Konstantinos , Suleiman Reem , Jeppesen Magnus Per Damsø , Weiss Catja , Christensen Søren Tvorup , Rivolta Carlo , Andersen Jens S. , Farinelli Pietro , Pedersen Lotte Bang 
Published: October 2020

AbstractCEP78 is a centrosomal protein implicated in ciliogenesis and ciliary length control, and mutations in theCEP78gene cause retinal cone-rod dystrophy associated with hearing loss. However, the mechanism by which CEP78 affects cilia formation is unknown. Based on a recently discovered disease-causingCEP78p.L150S mutation, we identified the disease-relevant interactome of CEP78. We confirmed that CEP78 interacts with the EDD1-DYRK2-DDB1VPRBPE3 ubiquitin ligase complex, which is involved in CP110 ubiquitination and degradation, and identified a novel interaction between CEP78 and CEP350 that is weakened by the CEP78L150Smutation. We show that CEP350 promotes centrosomal recruitment and stability of CEP78, which in turn leads to centrosomal recruitment of EDD1. Consistently, cells lacking CEP78 display significantly increased cellular and centrosomal levels of CP110, and depletion of CP110 in CEP78-deficient cells restored ciliation frequency to normal. We propose that CEP78 functions downstream of CEP350 to promote ciliogenesis by negatively regulating CP110 levels via an EDD1-dependent mechanism.
Dilemmas of empowering families of children with autism spectrum disorders: a qualitative case study
Authors: Khara Rouhallah , Kalankesh Leila R. , Shahrokhi Hassan , Dastgiri Saeed , Gholipour Kamal , Feizi-Derakhshi Mohammad-Reza 
Published: October 2020

Purpose
The purpose of this study was to identify the challenges and solutions in the empowerment of families of children with autism in Tabriz located in the North West of Iran.

Design/methodology/approach
In this exploratory and qualitative study, which was conducted from January to March 2019, 14 in-depth face-to-face interviews and 1 focus group (n = 5) were conducted with family empowerment experts. Data analysis was performed based on a content analysis approach via MAXQDA v 10.

Findings
Results revealed that empowerment challenges can be classified into six main themes including shortage of facilities and specialists, family-related problems, administrative and organizational, cultural and societal, financial and other problems. The most important empowerment solutions were divided into three main themes including informing and training skills by holding empowerment programs, governmental and insurance companies support, and organizational and administrative solutions.

Research limitations/implications
Limitation of this study is that families are not included; as families may also provide or challenge other solutions for empowerment based on their needs, ignoring their views may be losing part of vital information in this field. It is recommended that this research be conducted in the future from the perspective of families of people with autism and other stakeholders.

Practical implications
Based on the results of this study, stakeholders in the field of autism and the family empowerment can address the identified challenges and utilize solutions to improve the process of family empowerment and make more effective decisions in this regard.

Originality/value
Literature searches revealed a lack of any completed research in Iran specific to identifying empowerment challenges and related solutions. Efforts must be taken on root challenges which have been identified scientifically.
Customer perspectives on the acquisition of local artisanal companies
Authors: Legendre Tiffany Shin , Bowen John Thomas 
Published: October 2020

Purpose
The purpose of this study is to provide insight into customers’ psychological processes and behavioral responses after merger and acquisition (M&A) of an artisanal brand.

Design/methodology/approach
Study 1 adopts a qualitative approach to understand how craft-beer customers perceive M&A decisions. In Study 2, a two-conditioned (M&A types: local and local company M&A vs local and national company M&A) between-subjects design experiment was executed.

Findings
The findings of this study show M&A’s of artisanal brands cause identity stigmatization, resulting in customers’ identity dissonance and coping strategies. Which coping strategies a customer uses depends on their brand identity, product-category identity and M&A partner types.

Research limitations/implications
This was an exploratory study that serves as a starting point for future research. Future research could investigate the model proposed in this study by testing the effects of potential moderators and mediators.

Practical implications
The findings of the study enable companies to better anticipate post-M&A customer behavior, thereby enabling them to enhance their brand positioning when a competitor is acquired by a large company.

Originality/value
The popularity of locally produced and craft hospitality products has attracted the attention of large companies that acquire artisanal brands. There is a paucity of research investigating post- M&A customer reactions of locally owned artisanal companies by large companies.
The effect of corporate social responsibility transparency on corporate payout policies
Authors: Hendijani Zadeh Mohammad 
Published: October 2020

PurposeThis study explores whether a firm's environmental and social (E&S) transparency affects corporate payout policies having two forms of dividend payout and stock repurchase payout.Design/methodology/approachFocusing on a large sample of S&P 500 firms, and utilizing Tobit estimators, the author examines whether a firm's environmental transparency and social transparency affect the levels of each dividend payout and stock repurchase payout. Transparency reflects comprehensive scores compiled by Bloomberg, capturing both the quantity (in terms of the number of data points) and the quality (with respect to objective and industry-relevant data points) of verified E&S information attributed to a firm's E&S practices.FindingsThe findings demonstrate that transparency, both environmental and social, relates to higher corporate payouts (i.e. higher dividend payout and higher stock repurchase payout). These positive relationships are magnified for firms suffering from high information asymmetry, low financial reporting quality and for those with weak governance. Moreover, the author finds that dividend payout is more stable in high E&S transparent firms than in low E&S transparent firms. The study findings continue to hold after a battery of robustness and sensitivity checks such as alternative measures, specifications, estimators, use of the instrumental variable regression approach and mitigation of omitted variable biasResearch limitations/implicationsThe study findings suggest that investors' interests (demanding for high corporate payouts) and other stakeholders' interests (demanding for high E&S transparency) are not necessarily in conflict, and investors' demands can be met while maintaining commitment to high E&S transparency. In addition, the study results imply that higher E&S transparency complements higher corporate payouts and signals to the market both a firm's commitment to E&S transparency and its ability to have high corporate payouts. In this line, the study findings clarify the high value of E&S transparency screening in investors' decision-making process as such transparency leads to higher corporate payouts for investors (i.e. facilitating wealth transfer to shareholders). Finally, the study findings are relevant to standard setters and regulators who emphasize the importance of E&S transparency.Originality/valueBy integrating two distinct streams of literature on corporate finance and corporate social responsibility (CSR), the author introduces E&S transparency as a novel nonfinancial driver of corporate payout policies. Finally, the study findings are in line with the notion that firm transparency (reflected in E&S transparency) can be a crucial element in justifying a firm's corporate payout policies and, in an overall view, firm policies.
Performance measurement and management in the public sector: state of the art and research opportunities
Authors: Garengo Patrizia , Sardi Alberto 
Published: October 2020

PurposeSince the 1980s, performance measurement and management (PMM) has been described as an essential element of new public management (NPM) reforms. The purpose of this paper is to provide an overview of the current state of the art and future research opportunities for PMM in public sector management.Design/methodology/approachThe paper carried out a bibliometric literature review using two main techniques named (1) performance analysis and (2) science mapping techniques. It investigated the academic research area describing the main publications' trend, the conceptual structure and its evolution from 1996 to 2019.FindingsThe results highlighted the growing relevance of PMM research in public organisations and confirmed a great interest of the business, management and accounting literature on PMM in public sector management. Furthermore, the results also described a conceptual structure of the public PMM literature analysed and its evolution being too generic to answer public organisations' needs. The results identified five main research gaps and research opportunities.Originality/valueAlthough the adoption of rigorous bibliometric techniques was recognised as being useful for assessing the academic research study, the paper describes the business, management and accounting literature contributing to new theoretical and practical future opportunities.
Changes in the social work profession as responses to institutional multiplicity
Authors: Lyneborg Anna Olejasz 
Published: October 2020

PurposeAdopting the perspective of “institutional work” within neoinstitutionalism and “organizational professionalism” from the sociology of professions, this article contributes to current theoretical discussions on agency in settings of institutional multiplicity.Design/methodology/approachThis article investigates how social workers in Danish child protection services respond to the implementation of technologies of government targeted at shaping the conduct of conduct to achieve certain results. The article draws on a qualitative case study in a child protection agency and centers on the use of assessment committees as a case of technologies of government.FindingsThe article identifies divergent ways that social workers manage and make sense of contradiction, e.g. by means of detachment of accountability, expansion of practice and internalization of logics in professionalism. Thus, the article sheds light on how social workers cope with discrepant requirements fostered by technologies of government.Originality/valueAs research has focused on the potential constraining effects of technologies of government and discrepancy of logics, limited attention has been given to how the potential discrepancy is nevertheless reconciled, negotiated and handled in the everyday run-of-the-mill practice. Adopting the perspective of “institutional work” within neoinstitutionalism and “organizational professionalism” from the sociology of professions, this article contributes to current theoretical discussions on agency in settings of institutional multiplicity. Additionally, the article sheds light on how social workers manage and make sense of discrepant requirements fostered by technologies of government, reflecting empirical examples of a profession in transition.
Technological innovations in the work environment and the career of the millennium generation
Authors: Veloso Elza , Silva Rodrigo Cunha da , Trevisan Leonardo , Dutra Joel 
Published: October 2020

Purpose
The purpose of this paper is to identify the relationship of career anchors with three aspects: the millennials’ professional skills, the millennials’ awareness of the replacement of jobs with new technologies and the technological stress in the millennials’ working environment.

Design/methodology/approach
The responses of 200 questionnaires were analyzed using descriptive and variance analysis techniques.

Findings
Among the three hypotheses raised, two were confirmed, showing that these young people recognize the development of professional skills through new technologies, but are not highly sensitive to the stress associated with technological innovations.

Originality/value
The paper contributes to a recent debate, which emphasizes the impact of the application of new technologies on the nature of study and employment levels.