bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA Editing Signatures Predict Response to Immunotherapies in Melanoma Patients
Authors: Siddiqui Jalal , Miles Wayne O. 
Published: August 2020

Summary ParagraphImmunotherapy has improved the prognosis for half of the melanoma patients, prompting a need to understand differences between responding and non-responding patients. Gene expression profiling of tumors has focused on deriving primarily immune-related signatures, however these have shown limited predictive power. Recent studies have highlighted the role of RNA editing in modulating resistance to immunotherapy. This has led us to test whether RNA editing activity can be predictive of response in publicly available datasets of immunotherapy-treated melanoma patients. Here, we identified RNA editing signatures that were able to predict with very high accuracy and confidence patient responses and outcomes. Our analysis, however, demonstrates that RNA editing by itself is sufficient as a strong predictive tool for examining sensitivity of melanoma patients to immunotherapy.
APC/CFZR-1Controls ZYG-1 Levels to Regulate Centrosome Assembly
Authors: Medley Jeffrey C. , DiPanni Joseph R. , Schira Luke , Shaffou Blake M. , Sebou Brandon M. , Song Mi Hye 
Published: August 2020

AbstractAberrant centrosome numbers are associated with human cancers. The levels of centrosome regulators positively correlate with centrosome number. Thus, tight control of centrosome protein levels is critical. InCaenorhabditis elegans, the anaphase-promoting complex/cyclosome and co-activator FZR-1 (APC/CFZR-1) ubiquitin ligase negatively regulates centrosome assembly through SAS-5 degradation. In this study, we identify theC. elegansZYG-1 (Plk4 in human) as a new substrate of APC/CFZR-1. Inhibiting APC/CFZR-1or mutating a ZYG-1 destruction (D)-box leads to elevated ZYG-1 levels at centrosomes, restoring bipolar spindles and embryonic viability tozyg-1mutants, suggesting that APC/CFZR-1targets ZYG-1 for proteasomal degradation via D-box motif. We also show the Slimb/βTrCP-binding (SB) motif is critical for ZYG-1 degradation, substantiating a conserved mechanism by which ZYG-1/Plk4 stability is regulated by SCFSlimb/βTrCP-dependent proteolysis via the conserved SB motif inC. elegans. Furthermore, inhibiting both APC/CFZR-1and SCFSlimb/βTrCP, by co-mutating ZYG-1 SB and D-box motifs, stabilizes ZYG-1 in an additive manner, conveying that APC/CFZR-1and SCFSlimb/βTrCPubiquitin ligases function cooperatively for timely ZYG-1 destruction inC. elegansembryos where ZYG-1 activity remains at threshold level to ensure normal centrosome number.
Postembryonic screen for mutations affecting spine development in zebrafish
Authors: Gray Ryan S. , Gonzalez Roberto , Ackerman Sarah D. , Minowa Ryoko , Griest Johanna F. , Bayrak Melisa N. , Troutwine Benjamin , Canter Stephen , Monk Kelly R. , Sepich Diane S. , Solnica-Krezel Lilianna 
Published: August 2020

AbstractThe spinal vertebral column gives structural support for the adult body plan, protects the spinal cord, and provides muscle attachment and stability, which allows the animal to move within its environment. The development and maturation of the spine and its physiology involve the integration of multiple musculoskeletal tissues including bone, cartilage, and fibrocartilaginous joints, as well as innervation and control by the nervous system. One of the most common disorders of the spine in human is adolescent idiopathic scoliosis (AIS), which is characterized by the onset of an abnormal lateral curvature of the spine of <10° around adolescence, in otherwise healthy children. The genetic basis of AIS is largely unknown. Systematic genome-wide mutagenesis screens for embryonic phenotypes in zebrafish have been instrumental in the understanding of early patterning of embryonic tissues necessary to build and pattern the embryonic spine. However, the mechanisms required for postembryonic maturation and homeostasis of the spine remain poorly understood. Here we report the results from a small-scale forward genetic screen for adult-viable recessive and dominant mutant zebrafish, displaying overt morphological abnormalities of the adult spine. Germline mutations induced withN-ethylN-nitrosourea (ENU) were transmitted and screened for dominant phenotypes in 1,229 F1 animals, and subsequently bred to homozygosity in F3 families, from these, 314 haploid genomes were screened for recessive phenotypes. We cumulatively found 39 adult-viable (3 dominant and 36 recessive) mutations each leading to a defect in the morphogenesis of the spine. The largest phenotypic group displayed larval onset axial curvatures, leading to whole-body scoliosis without vertebral dysplasia in adult fish. Pairwise complementation testing within this phenotypic group revealed at least 16 independent mutant loci. Using massively-parallel whole genome or whole exome sequencing and meiotic mapping we defined the molecular identity of several loci for larval onset whole-body scoliosis in zebrafish. We identified a new mutation in theskolios/kinesin family member 6(kif6) gene, causing neurodevelopmental and ependymal cilia defects in mouse and zebrafish. We also report several recessive alleles of thescospondinanda disintegrin and metalloproteinase with thrombospondin motifs 9(adamts9) genes, which all display defects in spine morphogenesis. Many of the alleles characterized thus far are non-synonymous mutations in known essentialscospondinandadamts9genes. Our results provide evidence of monogenic traits that are critical for normal spine development in zebrafish, that may help to establish new candidate risk loci for spine disorders in humans.
Efferent feedback enforces bilateral coupling of spontaneous activity in the developing auditory system
Authors: Wang Yixiang , Sanghvi Maya , Gribizis Alexandra , Zhang Yueyi , Song Lei , Morley Barbara , Barson Daniel G. , Santos-Sacchi Joseph , Navaratnam Dhasakumar , Crair Michael 
Published: August 2020

SummaryIn the developing auditory system, spontaneous activity generated in the cochleae propagates into the central nervous system to promote circuit formation before hearing onset. Effects of the evolving peripheral firing pattern on spontaneous activity in the central auditory system are not well understood. Here, we describe the wide-spread bilateral coupling of spontaneous activity that coincides with the period of transient efferent modulation of inner hair cells from the medial olivochlear (MOC) system. Knocking out the α9/α10 nicotinic acetylcholine receptor, a requisite part of the efferent cholinergic pathway, abolishes these bilateral correlations. Pharmacological and chemogenetic experiments confirm that the MOC system is necessary and sufficient to produce the bilateral coupling. Moreover, auditory sensitivity at hearing onset is reduced in the absence of pre-hearing efferent modulation. Together, our results demonstrate how ascending and descending pathways collectively shape spontaneous activity patterns in the auditory system and reveal the essential role of the MOC efferent system in linking otherwise independent streams of bilateral spontaneous activity during the prehearing period.
A Novel Machine Learning Strategy for Prediction of Antihypertensive Peptides Derived from Food with High Efficiency
Authors: Wang Liyang , Niu Dantong , Wang Xiaoya , Shen Qun , Xue Yong 
Published: August 2020

AbstractStrategies to screen antihypertensive peptides with high throughput and rapid speed will be doubtlessly contributed to the treatment of hypertension. The food-derived antihypertensive peptides can reduce blood pressure without side effects. In present study, a novel model based on Extreme Gradient Boosting (XGBoost) algorithm was developed using the primary structural features of the food-derived peptides, and its performance in the prediction of antihypertensive peptides was compared with the dominating machine learning models. To further reflect the reliability of the method in real situation, the optimized XGBoost model was utilized to predict the antihypertensive degree of k-mer peptides cutting from 6 key proteins in bovine milk and the peptide-protein docking technology was introduced to verify the findings. The results showed that the XGBoost model achieved outstanding performance with the accuracy of 0.9841 and the area under the receiver operating characteristic curve of 0.9428, which were better than the other models. Using the XGBoost model, the prediction of antihypertensive peptides derived from milk protein was consistent with the peptide-protein docking results, and was more efficient. Our results indicate that using XGBoost algorithm as a novel auxiliary tool is feasible for screening antihypertensive peptide derived from food with high throughput and high efficiency.
Does the gender quota law affect bank performances? Evidence from Italy
Authors: Mazzotta Romilda , Ferraro Olga 
Published: August 2020

PurposeThis study aims to examine the impact of an increasing board diversity on the performance of Italian listed banks for the period 2008–2014, taking into account the effects of the implementation of gender quota laws in Italy. The study also investigates the effects of this potential relationship during the crisis that Italy had to cope with since 2011, as well as the potential impact of female directors and their roles on bank boards.Design/methodology/approachTo verify this relationship, the study uses a panel sample of 22 listed banks and applies fixed effects with the Driscoll-Kraay error. Considering the shareholders’ perspective, bank performance (BP) is measured by return on average equity. The robustness of results is verified through return on average assets, Tobin’s Q (a market measure from investors/stakeholders’ perspective) and an alternate estimation model, i.e. GMM.FindingsThe findings highlight a positive relationship between the performance accounting measures and gender diversity, a non-neutral impact of the presence of female directors on boards and a significant and negative effect on market measures.Research limitations/implicationsThe results of the study, as far as accounting measures are concerned, support managerial and legislative efforts toward more gender-balanced boards and the appointment of female directors in executive or independent roles. As per market measures, the results suggest that the presence of women on boards should be considered advantageous in terms of value, so that the market can finally appreciate diverse bank boards.Originality/valueFirst, previous studies did not provide exhaustive results to document the proposed relationship and did not examine this relationship during a financial crisis. Second, the role of female directors on boards is also taken into account. Third, the study highlighted that BP is a multi-dimensional construct, with accounting and market metrics being its distinct dimensions.
Balancing value and risk within a city's event portfolio: an explorative study of DMO professionals' assessments
Authors: Andersson Tommy D. , Getz Don , Jutbring Henrik 
Published: August 2020

PurposeThis study aims to advance both theory and praxis for event portfolio management in cities and destinations. An experiment has been conducted with professional event practitioners in a city to determine their opinions and strategies for balancing value and risk within their event portfolio. The first objective is to rank 14 of the city's recurring events in terms of both value and risk. Second, the events are plotted in a two-dimensional chart of value versus risk with the objective to differentiate between the 14 events. The third objective is to describe the event characteristics that event professionals associate with value and risk.Design/methodology/approachResults derive from an experiment involving the forced Q-sort procedure and professional event managers from a city renowned as an “event capital”. Empirical evidence is analysed by the constant comparative method of how events are being evaluated by ten professionals working for a DMO.FindingsEconomic impact and image effects are characteristics of high-value events as is an opportunity to create relations with event owners for future collaboration. Local community involvement is important for all events. The issue of portfolio fit was a common argument for weak-value events.Research limitations/implicationsResults are based on the opinions of ten DMO employees in one large city. Conclusions help build event portfolio theory.Practical implicationsThe results and methods are useful for event strategists and evaluators. In particular, the management of event portfolios and policies covering events in cities and destinations can benefit from the documented method for explicitly balancing risks with perceived value.Social implicationsA portfolio perspective is also suggested as an approach to analyse the total tourist attractions portfolio of a destination.Originality/valueOpinions regarding public value and risk by civil servants who work with events have not been studied before. The constant comparative method produces results that can be applied to policies governing events. In terms of theory development, concepts from financial portfolio management, product portfolio management and risk management are used to develop event portfolio design and management, and insights are gained on trade-offs in the process. The plot of the events in a two-dimensional chart of value versus risk clearly differentiated the 14 events and is an original contribution.
Segmentation of music festival visitors by values of hedonia, life satisfaction and eudaimonia
Authors: Saragih Harriman Samuel , Amelia Novi 
Published: August 2020

PurposeWith the growing interest in eudaimonia in the past years and the need to better understand festival visitors' motivation in the context of music festivals, this study aims to propose visitor segmentation based on the values of hedonia, life satisfaction and eudaimonia.Design/methodology/approachThe analysis in this study employs a case research method that follows the abductive paradigm. The authors begin their conceptual foundation with a review of the literature on hedonia, life satisfaction and eudaimonia. The authors then use the preliminary conceptual foundation as the basis of rival analysis through a focus group and interviews with senior executives, government officials, communities and other related stakeholders. The authors also carry out an exploratory factor analysis to determine the building blocks of eudaimonic festival experiences. Last, using cluster analysis, the authors support their conceptual proposition from the initial qualitative inquiries.FindingsFrom the three studies that the authors performed, their findings suggest that, based on hedonia and eudaimonia, festival attendees can be divided into three distinct segments: (1) pleasure seekers (i.e. visitors who look for personal pleasure, enjoyment and affection), (2) playful learners (i.e. visitors who not only seek pleasure, but also consider the urgency to think about the need to grow as a person) and (3) transcendentalists (i.e. visitors who seek a balance of pleasure, escapism, self-reflection, personal meaning and impact through attending festival activities).Research limitations/implicationsThis study argues that the ideas of hedonia and eudaimonia are present in the context of the music festival. Theoretically, this paper suggests that festival-goers can be divided into three clusters based on the values of hedonia and eudaimonia: pleasure seekers, playful learners and transcendentalists. Practically, this study suggests that festival organisers should consider developing music concert events by taking into account the eudaimonic and hedonistic desires, intrinsically possessed by the festival-goers, which is expected to add value to the produced musical event.Originality/valueThis study is the first to present visitor segmentation in a music festival setting based on the values of eudaimonia, life satisfaction and hedonia.
The medical university-governing board: an investigation of critical factors in the board performance in Iran
Authors: Sajadi Haniye Sadat , Maleki Mohammadreza , Michael Steve 
Published: August 2020

PurposeA university of medical sciences (UMS) is governed by a board that serves analogously as a board of trustees or a governing board in the western countries. In Iran, however, such boards operate under the broad leadership of the Ministry of Health and Medical Education (MoHME) but still wield enormous power over their universities. Given the influence boards have in the affairs of an UMS, the question remains how the medical university board can be improved so as to improve the overall effectiveness of these institutions. The purpose of this article is a response to this question by focusing on criteria necessary for reviewing board performance.Design/methodology/approachUsing a qualitative approach, the study solicited data from 37 key informants that were purposefully chosen from 52 medical science universities across Iran. Semi-structured face-to-face and phone interviews as well as a review of relevant document were the main means of the data gathering. We performed the framework analysis using software ATLAS-ti (version 5).FindingsThe analysis identified 32 overlapping indicators that must be considered in a board performance. These indicators were reclassified and summarized into six categories, including trustees, trustees' leadership, board structure, board process, board output (short-length results) and board outcomes (long-length results).Originality/valueOur study findings confirmed the role of the context and its relationship with the effective board performance. Here, the governing arrangement of all institutions including UMS is shadowed by the social, economic, cultural, political and technological status of the country. So, special attention is recommended to identify what should be considered to evaluate the performance of the board given the context.
Membership negotiation in the first workplace – Newcomers' experiences
Authors: Rajamäki Sari , Mikkola Leena 
Published: August 2020

PurposeThis qualitative study aims to understand young professional newcomers' experiences of communication processes in membership negotiation in their first workplace after graduation.Design/methodology/approachInstead of a one-time interview, the participants were contacted five to ten times during the three to ten months, beginning when they entered the workplace. The data were analyzed using a constant comparative method.FindingsThree communication processes during membership negotiation were identified: developing reciprocity, seeking and perceiving acceptance and becoming an active member. To experience membership, newcomers need to achieve acceptance and engage in reciprocal communication in early interaction situations with managers and coworkers.Research limitations/implicationsOnly the experiences of newly graduated newcomers were studied. This study illustrates the communication processes and social interaction evolving in membership negotiation during newcomers' entry.Practical implicationsOrganizations need to re-evaluate their short orientation programs to support membership negotiations in workplace communication.Social implicationsBy recognizing the communication processes during membership negotiation, the practices of newcomers' entry can be developed to support the membership development.Originality/valueThis study contributes to membership negotiation by showing how newcomers join the flow of membership negotiation through the processes of developing reciprocity, seeking and perceiving acceptance and becoming an active member.
In control we trust!? Exploring formal control configurations for municipally owned corporations
Authors: Krause Tobias Alexander , Swiatczak Martyna Daria 
Published: August 2020

PurposeThis study examines the interplay of formal types of control (input, behavior and outcome) exercised on municipally owned corporations (MOCs). It further investigates whether particular informal contingencies (trust and interdependence) predict affiliation to the derived municipal control configurations.Design/methodology/approachThe paper applies an exploratory cluster analysis based on survey data from 243 top-level managers of German MOCs. It then investigates the clustered municipal control configurations using binomial logistic regression.FindingsThe exploratory analysis reveals four municipal control configurations: (1) input-dominated control, (2) outcome-dominated control, (3) mixed input/outcome control and (4) “neglect of formal control”. As expected, both of the informal contingencies demonstrate strong predictive power. More precisely, trust increases the likelihood of belonging to the dominant outcome control cluster and interdependence increases the likelihood of belonging to the mixed input/outcome control cluster. Surprisingly, the neglect of formal control cluster is characterized by low trust and low interdependence.Originality/valueThe study sheds light on the widely assumed but understudied interplay of different formal controls in hybrid governance settings. Furthermore, the analysis stresses the importance of trust and interdependence when explaining hybrid control configurations.
Does CEO power matter for the performance of retrenchment strategy?
Authors: Brahmana Rayenda Khresna , You Hui Wei , Kontesa Maria 
Published: August 2020

PurposeThis research aims to examine the moderating role of CEO power on the relationship between retrenchment strategy and firm performance by framing the relationship under an agency theory, and power circulation theory.Design/methodology/approachThis study focuses on a sample of 319 non-financial public listed companies in Malaysia from the year 2011–2016 and estimates the model under two-step GMM panel regression to eliminate the endogeneity issue.FindingsThe results show that the retrenchment strategy increased firm performance. Meanwhile, greater CEO power changes that retrenchment effect into increased performance. This study also indicates the CEO power strengthens the relationship between firm performance and retrenchment. However, CEO power does not have any effect on the performance of low retrenchment, and the performance of big firm size.Research limitations/implicationsThe findings show that the higher CEO power cause higher firm performance and higher retrenchment. This research suggests that CEO power can make retrenchment strategy works and the decision made can affect the firm performance significantly.Originality/valueThis study examines the effect of CEO power on the performance of retrenchment strategy implementation by contesting agency theory, power circulation theory, and resource-based view theory within the emerging country context.