bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling Niemann-Pick disease type C in a human haploid cell line allows for patient variant characterization and clinical interpretation
Authors: Erwood Steven , Brewer Reid A. , Bily Teija M.I. , Maino Eleonora , Zhou Liangchi , Cohn Ronald D. , Ivakine Evgueni A. 
Published: October 2019

AbstractThe accurate clinical interpretation of human sequence variation is foundational to personalized medicine. This remains a pressing challenge, however, as genome sequencing becomes routine and new functionally undefined variants rapidly accumulate. Here, we describe a platform for the rapid generation, characterization and interpretation of genomic variants in haploid cells focusing on Niemann-Pick disease type C (NPC) as an example. NPC is a fatal neurodegenerative disorder characterized by a lysosomal accumulation of unesterified cholesterol and glycolipids. In 95% of cases, NPC is caused by mutations in the NPC1 gene, where over 200 unique disease-causing variants have been reported to date. Furthermore, the majority of patients with NPC are compound heterozygotes that often carry at least one private mutation, presenting a challenge for the characterization and classification of individual variants. Here, we have developed the first haploid cell model of NPC. This haploid cell model recapitulates the primary biochemical and molecular phenotypes typically found in patient-derived fibroblasts, illustrating its utility in modelling NPC. Additionally, we demonstrate the power of CRISPR-Cas9-mediated base editing in quickly and efficiently generating haploid cell models of individual patient variants in NPC. These models provide a platform for understanding the disease mechanisms underlying individual NPC1 variants while allowing for definitive clinical variant interpretation for NPC. While this study has focused on modelling NPC, the outlined approach could be translated widely and applied to a variety of genetic disorders or understanding the pathogenicity of somatic mutations in cancer.
A novel metabarcoded DNA sequencing tool for the detection of Plasmodium species in malaria positive patients
Authors: Wahab Abdul , Shaukat Ayaz , Ali Qasim , Hussain Mubashir , Khan Taj Ali , Khan M. Azmat Ullah , Rashid Imran , Saleem Mushtaq A. , Evans Mike , Sargison Neil D. , Chaudhry Umer 
Published: October 2019

AbstractVarious PCR based methods have been described for the diagnosis of malaria, but most depend on the use of Plasmodium species-specific probes and primers; hence only the tested species are identified and there is limited available data on the true circulating species diversity. Sensitive diagnostic tools and platforms for their use are needed to detect Plasmodium species in both clinical cases and asymptomatic infections that contribute to disease transmission. We have been recently developed for the first time a novel high throughput ‘haemoprotobiome’ metabarcoded DNA sequencing method and applied it for the quantification of haemoprotozoan parasites (Theleria and Babesia) of livestock. Here, we describe a novel, high throughput method using an Illumina MiSeq platform to demonstrate the proportions of Plasmodium species in metabarcoded DNA samples derived from human malaria patients. Plasmodium falciparum and Plasmodium vivax positive control gDNA was used to prepare mock DNA pools of parasites to evaluate the detection threshold of the assay for each of the two species and to assess the accuracy of proportional quantification. We then applied the assay to malaria-positive human samples to show the species composition of Plasmodium communities in the Punjab province of Pakistan and in the Afghanistan-Pakistan tribal areas. The diagnostic performance of the deep amplicon sequencing method was compared to an immunochromatographic assay that is widely used in the region. Metabarcoded DNA sequencing showed better diagnostic performance, greatly increasing the estimated prevalence of Plasmodium infection. The next-generation sequencing method using metabarcoded DNA has potential applications in the diagnosis, surveillance, treatment, and control of Plasmodium infections, as well as to study the parasite biology.
Conservation of an Ancient Oxidation Response That Controls Archaeal Epigenetic Traits Through Chromatin Protein Networks
Authors: Payne Sophie , Facciotti Marc , Cott Kevin Van , Yao Andrew , Wilson Mark , Sutter Stephan , Rodríguez-Acevedo Kiara L. , Blum Paul 
Published: October 2019

AbstractEpigenetic variants of the archaeonSulfolobus solfataricuscalled SARC have evolved heritable traits including extreme acid resistance, enhanced genome integrity and a conserved “SARC” transcriptome related to acid resistance. These traits appear to result from altered chromatin protein function related to the heritable hypomethylation of chromatin proteins Cren7 and Sso7D. To clarify how this might occur, ChIPseq and Affinity Purification Mass Spectrometry (AP-MS) were used to compare Cren7 and Sso7D genome binding sites and protein networks between lineages (wild type and SARC) and culture pH (pH 1 and 3). All SARC transcriptome loci were bound by these chromatin proteins but with invariant patterns indicating binding alone was insufficient to mediate the SARC traits. In contrast, chromosome association varied at other loci. Quantitative AP-MS was then used to identify protein interaction networks and these included transcription and DNA repair proteins implicated in the evolved heritable traits that varied in abundance between SARC and wild type strains. Protein networks included most of the S-adenosylmethionine (SAM) synthesis pathway including serine hydroxymethyltransferase (SHMT), whose abundance varied widely with culture pH. Because epigenetic marks are coupled to SAM pools and oxidative stress in eukaryotes, occurrence of a similar process was investigated here. Archaeal SAM pools were depleted by treatment with SAM pathway inhibitors, acid or oxidative stress and, like eukaryotes, levels were raised by vitamin B12 and methionine supplementation. We propose that in archaea, oxidation-induced SAM pool depletion acting through an SHMT sensor, drove chromatin protein hypomethylation and thereby protein network changes that established the evolved SARC epigenetic traits.Significance StatementArchaea and eukaryotes share many molecular processes, including chromatin-mediated epigenetic inheritance of traits. As with eukaryotes, archaeal protein complexes were formed between trait-related proteins and chromatin proteins, subject to chromatin protein methylation state. Oxidation-induced depletion of S-adenosylmethionine (SAM) pools likely resulted in chromatin protein hypomethylation. Subsequent chromatin enrichment of serine hydroxymethyltransferase as a response to oxidative stress could modulate methylation at specific genomic loci. The interplay between archaeal metabolism and chromatin appear consistent with patterns observed in eukaryotes and indicate the existence of an ancient oxidation signal transduction pathway controlling epigenetics.
Inference of population genetic structure from temporal samples of DNA
Authors: François Olivier , Liégeois Séverine , Demaille Benjamin , Jay Flora 
Published: October 2019

AbstractThe recent years have seen a growing number of studies investigating evolutionary questions using ancient DNA techniques and temporal samples of DNA. To address these questions, one of the most frequently-used algorithm is based on principal component analysis (PCA). When PCA is applied to temporal samples, the sample dates are, however, ignored during analysis, which could lead to some misinterpretations of the results. Here we introduce a new factor analysis (FA) method for which individual scores are corrected for the effect of allele frequency drift through time. Based on a diffusion approximation, our approach approximates allele frequency drift in a random mating population by a Brownian process. Exact solutions for estimates of corrected factors are obtained, and a fast estimation algorithm is presented. We compared data representations obtained from the FA method with PCA and with PC projections in simulations of divergence and admixture scenarios. Then we applied FA with correction for temporal drift to study the evolution of hepatitis C virus in a patient infected by multiple strains, and to describe the population structure of ancient European samples.
Dendrites with specialized glial attachments develop by retrograde extension using SAX-7 and GRDN-1
Authors: Cebul Elizabeth R. , McLachlan Ian G. , Heiman Maxwell G. 
Published: October 2019

ABSTRACTDendrites develop elaborate morphologies in concert with surrounding glia, but the molecules that coordinate dendrite and glial morphogenesis are mostly unknown.C. elegansoffers a powerful model for identifying such factors. Previous work in this system examined dendrites and glia that develop within epithelia, similar to mammalian sense organs. Here, we focus on the neurons BAG and URX, which are not part of an epithelium but instead form membranous attachments to a single glial cell at the nose, reminiscent of dendrite-glia contacts in the mammalian brain. We show that these dendrites develop by retrograde extension, in which the nascent dendrite endings anchor to the presumptive nose and then extend by stretch during embryo elongation. Using forward genetic screens, we find that dendrite development requires the adhesion protein SAX-7/L1CAM and the cytoplasmic protein GRDN-1/CCDC88C to anchor dendrite endings at the nose. SAX-7 acts in neurons and glia, while GRDN-1 acts in glia to non-autonomously promote dendrite extension. Thus, this work shows how glial factors can help to shape dendrites, and identifies a novel molecular mechanism for dendrite growth by retrograde extension.
Experimental investigation on lift generation of flapping MAV with insect wings of various species
Authors: S. Syam Narayanan , R. Asad Ahmed , Varghese Jijo Philip , S. Gopinath , Paulraj Jedidiah , M. Muthukumar 
Published: October 2019

Purpose
The purpose of this paper is to experimentally analyze the effect of wing shape of various insects of different species in a flapping micro aerial vehicle (MAV).

Design/methodology/approach
Six different wings are fabricated for the MAV configuration, which is restricted to the size of 15 cm length and width; all wings have different surface area and constant span length of 6 cm. The force is being measured with the help of a force-sensing resistor (FSR), and the coefficients of lift were calculated and compared.

Findings
This study shows that the wing “Tipula sp” has better value of lift than other insect wings, except for the negative angle of attacks. The wing “Aeshna multicolor” gives the better values of lift in negative angles of attack.

Practical implications
This paper lays the foundation for the development of flapping MAVs with the insect wings. This type of wing can be used for spying purpose in the military zone and also can be used to survey remote and dangerous places where humans cannot enter.

Originality/value
This paper covers all basic insect wing configurations of different species with exact mimics of the veins. As the experimental investigation was carried for different angle of attacks, velocities and flapping frequencies, this paper can be used as reference for future flapping wing MAV developers.
Modeling the critical barriers to implementation of AACSB accreditation in business schools
Authors: Kundu Goutam Kumar 
Published: October 2019

Purpose
The purpose of this paper is to identify and model the key barriers to the issue of adoption and implementation of AACSB accreditation standards in business schools. Business school management can focus on removing the key barriers and implement accreditation standards and practices to improve the quality of programs offered by them.

Design/methodology/approach
The present study adopts the interpretive structural modeling (ISM) approach to develop a hierarchical-based model of the key barriers to implementation of Advance Collegiate Schools of Business (AACSB) accreditation standards. It also depicts the mutual relationships among the key barriers.

Findings
The paper has identified the key barriers and presented an integrated model using ISM. Business schools need to pay maximum attention to diagnose and overcome these hindrances for effective implementation of AACSB accreditation standards.

Research limitations/implications
The model is based on the experts’ opinions, which may be biased, influencing the final output of the structural model. The developed model is to help the business school management in understanding the significance of the barriers, to prioritize or eliminate the same for the implementation of accreditation standards.

Originality/value
The depiction of barriers in the form of an ISM-based model is a new effort in the area of business school accreditation. The results will be useful to understand the barriers and overcome these for successful implementation of AACSB accreditation standards in business schools.
Mutuality or mutual dependence in the psychological contract: a power perspective
Authors: Ali Haris 
Published: October 2019

PurposeThere have been increasing calls to explore the psychological contract from the lens of power. By addressing this gap, the purpose of this paper is to investigate the assumption of mutuality in relation to power dynamics in the employment relationship.Design/methodology/approachA total of 43 in-depth interviews are conducted with 6 managerial and 37 non-managerial respondents in three major call center organizations in Pakistan. Template analysis is used to analyze the data.FindingsBy undermining the assumption of implicit mutuality, the analysis reveals indeterminacy, an issue that has been frequently underplayed in the psychological contract research. The results further suggest that – in reality – employability, flexibility and employee training do not promote mutuality to the extent that is theoretically assumed because of the employers’ manipulation of these issues in their own favor.Research limitations/implicationsThe focus on call centers limits the generality of findings with further qualitative research needed in other industries to explore how power asymmetries impact upon mutuality in different working environments.Practical implicationsThe research implications suggest the significance of timely and explicit communication in order to curtail indeterminacy in the employment relationship. This will not only reduce the development of breach perceptions among employees but will also reinforce their psychological contracts with the organization.Originality/valueThis research contributes by highlighting the significance of mutual dependence rather than mutuality in the psychological contract. The mutual dependence approach efficiently acknowledges the implications of power asymmetries which remain largely under-researched in the psychological contract theory.
Exploring the relationship of university students’ educational variables and the degree of their use of virtual social networks
Authors: Jalali Mansour , Bouyer Asgarali 
Published: October 2019

PurposeThe purpose of this paper is to explore relationships among the university students’ educational variables and their educational variables concerning educational, cultural and social dimensions.Design/methodology/approachA questionnaire was developed and validated for analyzing the relationship between the amount of time spent for using social networks and different dimensions of educational quality. The sample participants in this study included 400 students who were selected from a total of 3,500 students in Eastern and Western Azerbaijan provinces at north-west of Iran in 2017. Finally, 342 of 400 questionnaires were considered for analyzing. The Pearson and Spearman correlation coefficients and multiple regression were used to analyze data.FindingsThe results proved that the highest correlation coefficient was related to social networks and education quality and the lowest correlation was related to social networks and cultural quality. The result of applying multiple regression proved that there is a linear relationship between the roles of using social networks in predicting students’ educational quality.Originality/valueThe role of academic and general social media in studying students’ educational quality at universities is still under researched. This situation provides a significant potential to explore on the effect of academic and general virtual social media in creating educational and cultural awareness among university’s students. The findings of the current study add to the existing literature by contributing to a better awareness of university student and applying appropriate strategies to conduct the education of students.
A cost-benefit analysis model for the retrofit of sustainable urban drainage systems towards improved flood risk mitigation
Authors: Oladunjoye Oluwayemi A. , Proverbs David G. , Collins Beck , Xiao Hong 
Published: October 2019

PurposeThe Environment Agency estimates that one in six homes in England (approximately 5.2m properties) are at risk from flooding and 185,000 commercial properties are located in flood-prone areas. Further, an estimate of 10,000 new homes are built on flood plains yearly. The UK has witnessed a significant increase in flood events over the past 10 years. During this period, there has been growing research attention into measures to mitigate the effects of flooding, including the benefits of deploying sustainable urban drainage systems (SuDs) in new developments or as a retrofit. The purpose of this paper is to present the development of a cost-benefit analysis model for the retrofit of SuDs focusing on the potential for improved flood risk mitigation in the context of commercial properties.Design/methodology/approachA synthesis of flood risk management and SuDs literature is used to inform the development of a conceptual cost-benefit analysis model for the retrofit of SuDs and focusing on the potential for improved flood risk mitigation in the context of commercial properties.FindingsSuDs have been applied successfully in different parts of the world; however, the uptake of SuDs, in particular, the retrofit of SuDs, has been restricted by a number of issues including a lack of experience and trust in their performance and a lack of understanding in their true benefits. In particular, there is the limited experience of retrofitting SuDs and there are no well-established procedures for evaluating the feasibility, value or cost effectiveness of doing this.Social implicationsThis offers the potential to support the UK government’s flood risk management policy by helping to increase the resilience of properties, whilst offering other benefits to communities such as improvements in air quality and biodiversity and also presenting a clearer understanding of the monetary and non-monetary implication to owners of commercial properties for a more informed and acceptable uptake of SuDs retrofit.Originality/valueThe proposed model will allow a more comprehensive understanding of the costs and associated benefits associated with SuDs retrofit, highlighting the flood risk mitigation benefits that might accrue over a period of time for commercial property.
How operations matters in healthcare standardization
Authors: De Regge Melissa , Gemmel Paul , Meijboom Bert 
Published: October 2019

PurposeProcess management approaches all pursue standardization, of which evidence-based medicine (EBM) is the most common form in healthcare. While EBM addresses improvement in clinical performance, it is unclear whether EBM also enhances operational performance. Conversely, operational process standardization (OPS) does not necessarily yield better clinical performance. The authors have therefore looked at the relationship between clinical practise standardization (CPS) and OPS and the way in which they jointly affect operational performance. The paper aims to discuss this issue.Design/methodology/approachThe authors conducted a comparative case study analysis of a cataract surgery treatment at five Belgium hospital sites. Data collection involved 218 h of observations of 274 cataract surgeries. Both qualitative and quantitative methods were used.FindingsFindings suggest that CPS does not automatically lead to improved resource or throughput efficiency. This can be explained by the low level of OPS across the five units, notwithstanding CPS. The results indicate that a wide range of variables on different levels (patient, physician and organization) affect OPS.Research limitations/implicationsConsidering one type of care treatment in which clinical outcome variations are small complicates translating the findings to unstructured and complex care treatments.Originality/valueWith the introduction of OPS as a complementary view of CPS, the study clearly shows the potential of OPS to support CPS in practice. Operations matters in healthcare standardization, but only when it is managed in a deliberate way on a hospital and policy level.
Experimental study on the characteristic and function of oxide film formed on grinding wheel in ELID precision grinding
Authors: Zhang Jia-Bo , Yang Yang , Zhang Xiao-Hui , Guan Jia-Liang , Zheng Li-Yan , Li Guang 
Published: October 2019

Purpose
The purpose of this study is to investigate the characteristic and function of oxide film formed on grinding wheel in electrolytic in-process dressing (ELID) precision grinding and improve the quality of ELID grinding.

Design/methodology/approach
Dynamic film forming experiments were carried out with a simulation device close to the actual processing conditions. Then, the ELID grinding experiments of bearing rings were performed using grinding wheels with good film forming effect. The experiment was designed by quadratic regression general rotation combination method. The influence of grinding depth, electrolytic voltage, duty cycle and grinding wheel linear speed on grinding effect is analyzed.

Findings
A mathematical model for the formation rate of oxide film was established. The experiments show that the composition of grinding wheel and grinding fluid, as well as the electrical parameters, influence the film forming effect. Thus, the oxide film plays an important role in ELID grinding.

Originality/value
This study provides a reference for the design and selection of grinding wheel and grinding fluid and the setting of process parameters in ELID grinding.