bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD15 and CD15s expression is associated with G1 phase of the cell cycle in glioma cell lines
Authors: Jassam Samah A. , Maherally Zaynah , Chairta Paraskevi , Pilkington Geoffrey J. , Fillmore Helen L. 
Published: November 2020

AbstractOverexpression of the tetrasaccharide carbohydrate epitopes, CD15 and CD15s are associated with non-central nervous system malignancies. While CD15 and CD15s expression is rare in gliomas, recent reports suggest that CD15 may serve as a marker for brain tumour ‘stem-like’ cells. The aim of this study was to determine if this apparent discrepancy may, in part, be explained by temporal expression of CD15 and CD15s at different phases of the cell cycle. We used flow cytometry, immunocytochemistry and a fluorescence cell cycle indicator (FUCCI) system to examine expression in glioblastoma (GBM) cells (UP-007 and SNB-19) and non-neoplastic astrocytes (SC-1800) synchronised via serum starvation, Hydroxyurea and Nocodazole, respectively. CD15 and CD15s expression was significantly increased in glioma cells synchronised to G1 phase compared with non-synchronised cells (p<0.001). This was supported by qualitative results obtained with the (FUCCI) system. Few studies have considered the possibility of cell-cycle dependent CD15 and CD15s expression which may explain the inconsistencies reported in the literature in terms of expression in ‘glioma stem-like cells’ where cells are more likely in S phase where CD15 and CD15s expression would be low.
Rational Design and Synthesis of Selective PRMT4 Inhibitors: a New Chemotype for Development of Cancer Therapeutics
Authors: Sutherland Mathew , Li Alice , Kaghad Anissa , Panagopoulos Dimitrios , Li Fengling , Szewczyk Magdalena , Smil David , Scholten Cora , Bouché Léa , Stellfeld Timo , Arrowsmith Cheryl H. , Barsyte Dalia , Vedadi Masoud , Hartung Ingo V. , Steuber Holger , Britton Robert , Santhakumar Vijayaratnam 
Published: November 2020

ABSTRACTProtein arginine N-methyl transferase 4 (PRMT4) asymmetrically dimethylates arginine residues of histone H3 and non-histone proteins. The overexpression of PRMT4 in several cancers has stimulated interest in the discovery of inhibitors as biological tools and potentially therapeutics. While several PRMT4 inhibitors have been reported, most display poor selectivity against other members of the PRMT family of methyl transferases. Here, we report the structure-based design of a new class of alanine containing 3-arylindoles as potent and selective PRMT4 inhibitors and describe key structure activity relationships for this class of compounds.
Estimating time-varying selection coefficients from time series data of allele frequencies
Authors: Mathieson Iain 
Published: November 2020

AbstractTime series data of allele frequencies are a powerful resource for detecting and classifying natural and artificial selection. Ancient DNA now allows us to observe these trajectories in natural populations of long-lived species such as humans. Here, we develop a hidden Markov model to infer selection coefficients that vary over time. We show through simulations that our approach can accurately estimate both selection coefficients and the timing of changes in selection. Finally, we analyze some of the strongest signals of selection in the human genome using ancient DNA. We show that the European lactase persistence mutation was selected over the past 5,000 years with a selection coefficient of 2-2.5% in Britain, Central Europe and Iberia, but not Italy. In northern East Asia, selection at theADH1Blocus associated with alcohol metabolism intensified around 4,000 years ago, approximately coinciding with the introduction of rice-based agriculture. Finally, a derived allele at theFADSlocus was selected in parallel in both Europe and East Asia, as previously hypothesized. Our approach is broadly applicable to both natural and experimental evolution data and shows how time series data can be used to resolve fine-scale details of selection.
Ethical and psychosocial considerations for hospital personnel in the Covid-19 crisis: Moral injury and resilience
Authors: Kreh Alexander , Brancaleoni Rachele , Magalini Sabina Chiara , Rosaria Chieffo Daniela Pia , Flad Barbara , Ellebrecht Nils , Juen Barbara 
Published: November 2020

AbstractThis study aims at investigating the nature of resilience and stress experience of health care workers during the COVID-19 pandemic. Thirteen healthcare workers from Italian and Austrian hospitals specifically dealing with COVID-19 patients during the first phase of the pandemic were interviewed. Data was analysed using grounded theory methodology. Psychosocial effects on stress experience, stressors and resilience factors were identified. We generated three hypotheses. Hypothesis one is that moral distress and moral injury are main stressors experienced by healthcare workers. Hypothesis two states that organisational resilience plays an important part in how healthcare workers experience the crisis. Organisational justice and decentralized decision making are essential elements of staff wellbeing. Hypothesis three refers to effective psychosocial support: Basic on scene psychosocial support based on the Hobfoll principles given by trusted and well-known mental health professionals and peers in an integrated approach works best during the pandemic.
Evidence for Numerous Embedded Antisense Overlapping Genes in DiverseE. coliStrains
Authors: Zehentner Barbara , Ardern Zachary , Kreitmeier Michaela , Scherer Siegfried , Neuhaus Klaus 
Published: November 2020

SUMMARYThe genetic code allows six reading frames at a double-stranded DNA locus, and many open reading frames (ORFs) overlap extensively with ORFs of annotated genes (e.g., at least 30 bp or having an embedded ORF). Currently, bacterial genome annotation systematically discards embedded overlapping ORFs of genes (OLGs) due to an assumed information-content constraint, and, consequently, very few OLGs are known. Here we use strand-specific RNAseq and ribosome profiling, detecting about 200 embedded or partially overlapping ORFs of gene candidates in the pathogenE. coliO157:H7 EDL933. These are typically short, many of them show clear promoter motifs as determined by Cappable-seq, indistinguishable from those of annotated genes, and are expressed at a low level. We could express most of them as stable proteins, and 49 displayed a potential phenotype. Ribosome profiling analyses in three otherE. colistrains predicted between 84 and 190 embedded antisense OLGs per strain except inE. coliK-12, which is an atypical lab strain. We also found evidence of homology to annotated genes for 100 to 300 OLGs perE. colistrain investigated. Based on this evidence we suggest that bacterial OLGs deserve attention with respect to genome annotation and coding complexity of bacterial genomes. Such sequences may constitute an important coding reserve, opening up new research in genetics and evolutionary biology.
High-dimensional association detection in large scale genomic data
Authors: Koch Hillary , Keller Cheryl A. , Xiang Guanjue , Giardine Belinda , Zhang Feipeng , Wang Yicheng , Hardison Ross C. , Li Qunhua 
Published: November 2020

AbstractJoint analyses of genomic datasets obtained in multiple different conditions are essential for understanding the biological mechanism that drives tissue-specificity and cell differentiation, but they still remain computationally challenging. To address this we introduce CLIMB (Composite LIkelihood eMpirical Bayes), a statistical methodology that learns patterns of condition-specificity present in genomic data. CLIMB provides a generic framework facilitating a host of analyses, such as clustering genomic features sharing similar condition-specific patterns and identifying which of these features are involved in cell fate commitment. We apply CLIMB to three sets of hematopoietic data, which examine CTCF ChIP-seq measured in 17 different cell populations, RNA-seq measured across constituent cell populations in three committed lineages, and DNase-seq in 38 cell populations. Our results show that CLIMB improves upon existing alternatives in statistical precision, while capturing interpretable and biologically relevant clusters in the data.
The ChiS-family DNA-binding domain contains a cryptic helix-turn-helix variant
Authors: Klancher Catherine A. , Minasov George , Podicheti Ram , Rusch Douglas B. , Dalia Triana N. , Satchell Karla J. F. , Neiditch Matthew B. , Dalia Ankur B. 
Published: November 2020

AbstractSequence specific DNA-binding domains (DBDs) are conserved in all domains of life. These proteins carry out a variety of cellular functions, and there are a number of distinct structural domains already described that allow for sequence-specific DNA binding, including the ubiquitous helix-turn-helix (HTH) domain. In the facultative pathogenVibrio cholerae, the chitin sensor ChiS is a transcriptional regulator that is critical for the survival of this organism in its marine reservoir. We have recently shown that ChiS contains a cryptic DBD in its C-terminus. This domain is not homologous to any known DBD, but it is a conserved domain present in other bacterial proteins. Here, we present the crystal structure of the ChiS DBD at a resolution of 1.28 Å. We find that the ChiS DBD contains an HTH domain that is structurally similar to those found in other DNA binding proteins, like the LacI repressor. However, one striking difference observed in the ChiS DBD is that the canonical tight “turn” of the HTH is replaced with an insertion containing a β-sheet, a variant which we term the “helix-sheet-helix”. Through systematic mutagenesis of all positively charged residues within the ChiS DBD, we show that residues within and proximal to the ChiS helix-sheet-helix are critical for DNA binding. Finally, through phylogenetic analyses we show that the ChiS DBD is found in diverse Proteobacterial proteins that exhibit distinct domain architectures. Together, these results suggest that the structure described here represents the prototypical member of the ChiS-family of DBDs.ImportanceRegulating gene expression is essential in all domains of life. This process is commonly facilitated by the activity of DNA-binding transcription factors. There are diverse structural domains that allow proteins to bind to specific DNA sequences. The structural basis underlying how some proteins bind to DNA, however, remains unclear. Previously, we showed that in the major human pathogenVibrio choleraethe transcription factor ChiS directly regulates gene expression through a cryptic DNA binding domain. This domain lacked homology to any known DNA-binding protein. In the current study, we determined the structure of the ChiS DNA binding domain (DBD) and find that the ChiS-family DBD is a cryptic variant of the ubiquitous helix-turn-helix (HTH) domain. We further demonstrate that this domain is conserved in diverse proteins that may represent a novel group of transcriptional regulators.
Shift-field refinement of macromolecular atomic models
Authors: Cowtan K. , Metcalfe S. , Bond P. 
Published: November 2020

The aim of crystallographic structure solution is typically to determine an atomic model which accurately accounts for an observed diffraction pattern. A key step in this process is the refinement of the parameters of an initial model, which is most often determined by molecular replacement using another structure which is broadly similar to the structure of interest. In macromolecular crystallography, the resolution of the data is typically insufficient to determine the positional and uncertainty parameters for each individual atom, and so stereochemical information is used to supplement the observational data. Here, a new approach to refinement is evaluated in which a `shift field' is determined which describes changes to model parameters affecting whole regions of the model rather than individual atoms only, with the size of the affected region being a key parameter of the calculation which can be changed in accordance with the resolution of the data. It is demonstrated that this approach can improve the radius of convergence of the refinement calculation while also dramatically reducing the calculation time.
The love of money and the propensity to engage in unethical behaviours: a study in the Portuguese context
Authors: Oliveira Filipa , Marques Tânia M.G. 
Published: November 2020

PurposeThis work aims to study the relationship between individuals' love of money and their propensity to engage in unethical behaviour.Design/methodology/approachData were collected through a questionnaire, with the final sample consisting of 297 Portuguese individuals. The hypotheses were tested using linear regression models.FindingsThe results demonstrate that there is no significant relationship between the love of money and the propensity to engage in unethical behaviour. However, there was a significant relationship between the level of budgeting and the propensity to engage in unethical behaviours – for those individuals who have a greater ability to manage their money are less likely to engage in behaviours unethical. The existence of a significant relationship between the “evil” factor and the propensity to engage in unethical behaviour was also validated, which demonstrates that when individuals both associate negative feelings with money and consider love of money to be the “root of evil”, then they are less likely to be involved in unethical behaviour.Originality/valueThis work contributes theoretically and empirically to a better understanding of individuals' attitudes towards money and their propensity to engage in unethical behaviour. The results are of particular academic and organisational relevance due to the implications for human resource management.
How accessories add value to a platform: the role of innovativeness and nonalignability
Authors: Gill Tripat , Ma Zhenfeng , Zhao Ping , Chen Yongjian (Ken) 
Published: November 2020

PurposeThis study aims to distinguish between the indispensable (software) versus discretionary (accessories) complementary products to a platform. It investigates the impact of accessories on increasing the perceived value and sales of a base platform. In particular, the role of two distinct characteristics of accessories – innovativeness and structural nonalignability – in driving the sales of the base platform.Design/methodology/approachCombining sales data from the US video gaming industry with primary data on the above two aspects of accessories, this study quantifies the effect of accessories portfolio on the sales of three brands of video gaming platforms.FindingsA distinct network externality arises from accessories for video gaming platforms, above and beyond the effects of game titles. Importantly, the average level of innovativeness and nonalignability of the accessories portfolio, as well as the frequency of introduction of highly innovative and/or nonalignable accessories positively impact the sales of the platform.Research limitations/implicationsThis research seeks to address the gap in the innovation literature on the role of discretionary complementary products (i.e. accessories) on platform sales. Future research should examine this in other platform contexts as well.Practical implicationsManagers of platform-mediated products should give due consideration to accessories, as an important driver of the sales of the platforms. Product managers can leverage the advantage of innovative and nonalignable accessories to enhance consumer demand for the platform.Originality/valueThis study is the first to conceptualize and empirically verify the network externality arising from accessories, a heretofore much neglected component of platform-based markets.
The impact of AAOIFI governance disclosure on Islamic banks performance
Authors: Elgattani Tawida , Hussainey Khaled 
Published: November 2020

Purpose
This study aims to investigate the impact of the accounting and auditing organisation for Islamic financial institution (AAOIFI) governance disclosure on the performance of Islamic banks (IBs).

Design/methodology/approach
The ordinary least squares regression model was used to test the impact of AAOIFI governance disclosure on the performance of 126 IBs from 8 countries that mandatorily adopt the AAOIFI standards for three years (2013–2015). In this regression model, return on asset (ROA) and return on equity (ROE) are the dependent variables, while AAOIFI governance disclosure is the independent variable. Corporate governance mechanisms, firm characteristics, year dummy and country dummy are used as control variables.

Findings
This paper found an insignificant relationship between AAOIFI governance disclosure and IBs performance.

Research limitations/implications
This study highlighted the implication that the current research may help IBs and encourage them to disclose more information in annual reports, especially those related to AAOIFI governance standards because following good corporate governance leads to good financial performance. The major limitation of the paper is that it is only focussed on two measurements of bank performance – ROA and ROE; it would be good to use other firm performance measures, such as profit margin.

Originality/value
This study provides new empirical evidence on the impact of AAOIFI governance disclosure on IBs performance.
Empowering employees: the other side of electronic performance monitoring
Authors: Sherif Karma , Jewesimi Omolola , El-Masri Mazen 
Published: November 2020

Purpose
Advances in electronic performance monitoring (EPM) have raised employees’ concerns regarding the invasion of privacy and erosion of trust. On the other hand, EPM promises to improve performance and processes. This paper aims to focus on how the alignment of EPM design and organizational culture through effective organizational mechanisms can address privacy concerns, and, hence, positively affect employees’ perception toward technology.

Design/methodology/approach
Based on a theoretical lens extending two conceptual frameworks, a qualitative approach was used to analyze interview data collected from a comparative case study of two organizations in the USA and Qatar within the oil and gas sector. These two contexts were selected to emphasize the cross-cultural and organizational differences in employees’ acceptance of EPM.

Findings
The study revealed that national and corporate cultures affected employees’ perception and acceptance of monitoring in both countries. Because of diversity, though EPM was better accepted in Qatar, as they are an easy way to enforce standardization and to push employees to adapt to a dominating corporate culture. Conversely, in the USA where culture is more innovation-oriented, organizational mechanisms shifted the perceptions of EPM to being mean to obtain feedback rather than to impose standards.

Research limitations/implications
This qualitative study is based on a descriptive comparative case study of two organizations with two cultural contexts. The limited sample size and cross-sectional nature of data may need to be extended to a larger cultural scope that is observed over a longer period to safely generalize the findings.

Practical implications
Decision-makers in multinational corporations with different cultural backgrounds may benefit of this study’s outcomes, as it emphasizes the importance of the fit between EPM designs and the cultural settings. Furthermore, organizations aiming to conduct analytics on EPM data have to justify and prove its benefits to employees to facilitate acceptance.

Social implications
The study shows that employees in Qatar have a different cultural frame of reference in their perception of fairness and ethics than their counterparts in the USA because of changes in the meaning of social relations, personal goals and behavioral norms.

Originality/value
The originality of this study lays in its empirical validation of a composite framework examining both national and corporate cultures on employees’ reactions to EPM systems. It also proves the critical importance of organizational mechanisms to align the EPM design with the organization cultural settings.
Renal water conservation and the volume kinetics of fluid‐induced diuresis: A retrospective analysis of two cohorts of elderly men
Authors: Hahn Robert G. 
Published: November 2020

AbstractRenal water conservation after an overnight fast mirrors the habitual intake of liquid. The hypothesis in the present study was that water conservation influences the diuretic response to infusion of two types of crystalloid fluid. Twenty‐three elderly male patients (mean age 72 years) underwent a total of 46 intravenous infusions of 1.0 or 1.5 L of either hypotonic non‐electrolyte fluid (glycine 1.5%) or isotonic electrolyte fluid (Ringer's acetate or 0.9% saline). Urine osmolality (used to indicate renal water conservation) and plasma creatinine were measured before the infusions started. A two‐volume model was fitted to repeated measurements of the blood haemoglobin concentration and the urinary excretion, using mixed‐effects modelling software. Urine osmolality was examined as a potential covariate to the fixed kinetic parameters. The results show that distribution and redistribution of infused fluid occurred twice as fast for the non‐electrolyte fluids as for the electrolyte‐containing fluids, while the urine flow showed less difference. For both types of fluid, high urine osmolality served as a statistically significant covariate to the rate constant describing urinary excretion. Simulations showed that a high pre‐infusion urine osmolality doubled the time required for the kidneys to excrete 50% of a 30‐minute infusion. High plasma creatinine independently prolonged the elimination of non‐electrolyte fluid. The use of 0.9% saline instead of Ringer's prolonged the excretion of electrolyte‐containing fluid. In conclusion, renal water conservation is a determinant of the diuretic response to crystalloid fluid, regardless of whether the fluid contains electrolytes, and it should be considered in fluid balance studies.
A Danish terminological ontology of incident management in the field of disaster management
Authors: Christensen Lise Lotte Weilgaard , Madsen Bodil Nistrup 
Published: November 2020

AbstractLack of concept clarification based on concept modelling results in inappropriate term use and inefficient information and communication technology. In this contribution, we refer to the fire aboard the ship Scandinavian Star in 1990 and the terror attack at Utøya in 2011 as examples. We establish a terminological ontology for 46 Danish concepts included in an alphabetically organized term list on incident management by the Danish Emergency Management Agency (DEMA). Based on this ontology, the main aim is to demonstrate how terminological principles may form the basis for creating structured data, which may support a common understanding of domain‐specific key concepts which again is a prerequisite for successful and well‐functioning disaster management systems. The terminological method will be explained, focusing on terminological ontologies and terminological definitions reflecting the semantic structure of the domain. Further, we illustrate the use of technology for knowledge modelling and sharing, and we briefly describe how the results of terminology work may be stored in a term bank in order to support common understanding and efficient communication. Moreover, terminological ontologies may lay the foundation for data models for disaster management systems, technologies involving Artificial Intelligence, and building blocks of semantic technologies.