bluuebunny/crossref_metadata_2025_split huggingface dataset:
Local CpG density affects the trajectory of age-associated epigenetic changes
Authors: Higham Jonathan , Zhang Qian , Walker Rosie M. , Harris Sarah E. , Howard David M. , Hawkins Emma L. , Sandu Anca-Larisa , Steele J. Douglas , Waiter Gordon D. , Murray Alison D. , Evans Kathryn L. , McIntosh Andrew M. , Visscher Peter M. , Deary Ian J. , Cox Simon R. , Sproul Duncan 
Published: July 2021

AbstractDNA methylation is an epigenetic mark associated with gene repression and genome stability. Its pattern in the genome is disrupted with age and these changes can be used to statistically predict age with epigenetic clocks. Rates of aging inferred from these clocks correlate with human health. However, the molecular mechanisms underpinning age-associated DNA methylation changes are unknown. Local DNA sequence plays a strong role in programming DNA methylation levels at individual loci independently of age, but its influence on age-associated DNA methylation changes is unknown. We analysed longitudinal human DNA methylation trajectories at 345,895 CpGs from 600 individuals aged between 67 and 80 to understand the factors responsible for age-associated epigenetic changes at individual CpGs in the genome. We show that changes in methylation with age are especially apparent at 8,322 low CpG density loci. Using SNP data from the same individuals we demonstrate that DNA methylation trajectories are affected by local sequence polymorphisms at 1,487 loci with low CpG density. More generally, we find that local CpG density is a strong determinant of a CpG’s methylation trajectory and that CpGs located in low CpG density regions are particularly prone to change. Overall, our results demonstrate that local DNA sequence influences age-associated DNA methylation changes in humans in vivo. We suggest that this occurs because interactions between CpGs reinforce maintenance of methylation patterns in CpG dense regions.
In Silico Defined SARS-CoV2 Epitopes May Not Predict Immunogenicity to COVID19
Authors: Pan Ke , Chiu Yulun , Chen Michelle , Wang Junmei , Lai Ivy , Singh Shailbala , Shaw Rebecca , Yee Cassian 
Published: July 2021

AbstractSARS-CoV-2 infections elicit both humoral and cellular immune responses. For the prevention and treatment of COVID19, the disease caused by SARS-CoV-2, it has become increasingly apparent that T cell responses are equally, if not more important than humoral responses in mediating recovery and immune-protection. One of the major challenges in developing T cell-based therapies for infectious and malignant diseases has been the identification of immunogenic epitopes that can elicit a meaningful T cell response. Traditionally, this has been achieved using sophisticatedin silicomethods to predict putative epitopes deduced from binding affinities and consensus data. Our studies find that, in contrast to current dogma, ‘immunodominant’ SARS-CoV-2 peptides defined by suchin silicomethods often fail to elicit T cell responses recognizing naturally presented SARS-CoV-2 epitopes.
Tactile motor attention induces sensory attenuation for sounds
Authors: Fritz Clara , Flick Mayra , Zimmermann Eckart 
Published: July 2021

AbstractSensory events appear reduced in intensity when we actively produce them. Here, we investigated sensory attenuation in a virtual reality setup that allowed us to manipulate the time of tactile feedback when pressing a virtual button. We asked whether tactile motor attention might shift to the tactile location that makes contact with the button. In experiment one, we found that a tactile impulse was perceived as more intense when button pressing. In a second experiment, participants pushed a button and estimated the intensity of sounds. We found sensory attenuation for sounds only when tactile feedback was provided at the time the movement goal was reached. These data indicate that attentional prioritization for the tactile modality during a goal-directed hand movement might lead to a transient reduction in sensitivity in other modalities, resulting in sensory attenuation for sounds.
Centriole distal-end proteins CP110 and Cep97 influence centriole cartwheel growth at the proximal-end
Authors: Aydogan Mustafa G. , Hankins Laura E. , Steinacker Thomas L. , Mofatteh Mohammad , Saurya Saroj , Wainman Alan , Wong Siu-Shing , Lu Xin , Zhou Felix Y. , Raff Jordan W. 
Published: July 2021

SummaryCentrioles are composed of a central cartwheel tethered to nine-fold symmetric microtubule (MT) blades. The centriole cartwheel and MTs are thought to grow from opposite ends of these organelles, so it is unclear how they coordinate their assembly. We previously showed that an oscillation of Polo-like kinase 4 (Plk4) helps to initiate and time the growth of the cartwheel at the proximal end. Here, we show that CP110 and Cep97 form a complex close to the distal-end of the centriole MTs whose levels rise and fall as the new centriole MTs grow, entrained by the core Cdk/Cyclin oscillator that drives the nuclear divisions in these embryos. These CP110/Cep97 dynamics, however, do not appear to time the period of centriole MT growth directly. Instead, we find that changing the levels of CP110/Cep97 alters the Plk4 oscillation and the growth of the cartwheel at the proximal end. These findings reveal an unexpected crosstalk between factors normally concentrated at opposite ends of the growing centrioles, which may help to coordinate centriole growth.
Evaluation of intranasal nafamostat or camostat for SARS-CoV-2 chemoprophylaxis in Syrian golden hamsters
Authors: Neary M , Box H , Sharp J , Tatham L , Curley P , Herriott J , Kijak E , Arshad U , Hobson JJ , Rajoli RKR , Pertinez H , Valentijn A , Dhaliwal K , McCaughan F , Rannard SP , Kipar A , Stewart JP , Owen A 
Published: July 2021

AbstractSuccessful development of a chemoprophylaxis against SARS-CoV-2 could provide a tool for infection prevention implementable alongside vaccination programmes. Camostat and nafamostat are serine protease inhibitors that inhibit SARS-CoV-2 viral entry in vitro but have not been characterised for chemoprophylaxis in animal models. Clinically, nafamostat is limited to intravenous delivery and while camostat is orally available, both drugs have extremely short plasma half-lives. This study sought to determine whether intranasal dosing at 5 mg/kg twice daily was able to prevent airborne transmission of SARS-CoV-2 from infected to uninfected Syrian golden hamsters. SARS-CoV-2 viral RNA was above the limits of quantification in both saline- and camostat-treated hamsters 5 days after cohabitation with a SARS-CoV-2 inoculated hamster. However, intranasal nafamostat-treated hamsters remained RNA negative for the full 7 days of cohabitation. Changes in body weight over the course of the experiment were supportive of a lack of clinical symptomology in nafamostat-treated but not saline- or camostat-treated animals. These data are strongly supportive of the utility of intranasally delivered nafamostat for prevention of SARS-CoV-2 infection and further studies are underway to confirm absence of pulmonary infection and pathological changes.
Cytoplasmic Switch of ARS2 Isoforms Promotes Nonsense-Mediated mRNA Decay and Arsenic Sensitivity
Authors: Mesa-Perez Monica , Hamilton Phineas T. , Miranda-Rodriguez Alex , Brodie Nicholas , O’Sullivan Connor , Christie Jennifer , Ryan Bridget C. , Chow Robert L. , Goodlett David , Nelson Christopher J. , Howard Perry L. 
Published: July 2021

AbstractThe life of RNA polymerase II (RNAPII) transcripts is shaped by the dynamic formation of mutually exclusive ribonucleoprotein complexes (RNPs) that direct transcript biogenesis and turnover. A key regulator of RNA metabolism in the nucleus is the scaffold protein ARS2 (arsenic resistance protein 2), bound to the cap binding complex (CBC). We report here that alternative splicing of ARS2’s intron 5, generates cytoplasmic isoforms that lack 270 amino acids from the N-terminal of the protein and are functionally distinct from nuclear ARS2. Switching of ARS2 isoforms within the CBC in the cytoplasm has dramatic functional consequences, changing ARS2 from a NMD inhibitor to a NMD promoter that enhances the binding of UPF1 to NCBP1, ERF1 and DHX34, favouring SURF complex formation, SMG7 recruitment and transcript degradation. ARS2 isoform exchange is also relevant during arsenic stress, where cytoplasmic ARS2 promotes a global response to arsenic in a CBC-independent manner. We propose that ARS2 isoform switching promotes the proper recruitment of RNP complexes during NMD and the cellular response to arsenic stress. The existence of non-redundant ARS2 isoforms is relevant for cell homeostasis, stress response, and cancer treatment.
Glycocalyx engineering with heparan sulfate mimetics attenuates Wnt activity during adipogenesis to promote glucose uptake and metabolism
Authors: Trieger Greg W. , Pessentheiner Ariane R. , Purcell Sean C. , Green Courtney R. , DeForest Natalie , Willert Karl , Majithia Amit R. , Metallo Christian M. , Godula Kamil , Gordts Philip L. S. M. 
Published: July 2021

ABSTRACTAdipose tissue (AT) plays a crucial role in maintaining me tabolic homeostasis by storing lipids and glucose from circulation as intracellular fat. As peripheral tissues like AT become insulin resistant, decompensation of blood glucose levels occurs causing type 2 diabetes (T2D). Currently, glycocalyx modulating as a pharmacological treatment strategy to improve glucose homeostasis in T2D patients is underexplored. Here, we show a novel role for cell surface heparan sulfate (HS) in establishing glucose uptake capacity and metabolic utilization in differentiated adipocytes. Using a combination of chemical and genetic interventions, we identified that HS modulates this metabolic phenotype by attenuating levels of Wnt signaling during adipogenesis. By engineering the glycocalyx of preadipocytes with exogenous synthetic HS mimetics, we were able to enhance glucose clearance capacity after differentiation through modulation of Wnt ligand availability. These findings establish the cellular glycocalyx as a possible new target for therapeutic intervention in T2D patients by enhancing glucose clearance capacity independent of insulin secretion.SIGNIFICANCEMetabolic disorders associated with the Western-style diet, such as type 2 diabetes, are among the main drivers of mortality in the US and globally, with more than 380 million people currently affected by this disease worldwide. However, treatment options for type 2 diabetes are currently limited to management of caloric uptake and expenditure, with none able to reverse the condition long-term. The ability to reprogram adipose tissues to improve their overall capacity to clear glucose may provide one such opportunity. Here we provide evidence that glycocalyx remodeling in pre-adipocytes with heparan sulfate mimetics will alter their differentiation program by modulating Wnt signaling to produce adipocytes with increased glucose uptake and utilization.
Analysis of operational and financial performance of ports: an integrated fuzzy DEMATEL-TOPSIS approach
Authors: Gayathri C. , Kamala V. , Gajanand M.S. , Yamini S. 
Published: July 2021

PurposePorts handle a significant portion of international cargo, so the performance of ports plays a major role in the economic development of a country. This paper aims to study how port performance depends on various interdependent factors and how it requires a holistic approach, which accounts for all the necessary criteria that contribute to the overall efficiency and performance.Design/methodology/approachAn integrated fuzzy DEMATEL-TOPSIS approach with an objective to evaluate the operational capability and financial performance of the ports is proposed. A case study is presented with an analysis of the major South Indian ports to assess port operational performance and evaluate various financial ratios to assess financial performance.FindingsThrough a review of the literature and based on the inputs from experts, six criteria affecting the operational performance and six financial criteria were identified. The debt coverage ratios turned out to be the most important, while the liquidity ratios were the least important. The six operational criteria have almost similar importance. The final results indicate a consistent overall performance by the Ennore Port, except during one financial year.Practical implicationsThe proposed solution approach helps to identify and concentrate on the criteria that affect port performance. It will also help to evaluate and understand the dynamics involved in the performance of ports.Originality/valueThis work highlights the key measurable operational and financial criteria that affect the efficiency of ports. The integrated fuzzy DEMATEL-TOPSIS approach provides a better way to evaluate and benchmark port performance.
The effect of servant leadership on innovative work behavior and employee knowledge sharing in the Latvian ICT sector
Authors: Bou Reslan Fadi Youssef , Garanti Zanete , Emeagwali Okechukwu Lawrence 
Published: July 2021

PurposeThis study aims to peruse the underlying effect of servant leadership (SL) on innovative work behavior (IWB) and employee knowledge sharing behavior (KSB), directly and through the mediating effect of job autonomy (JA), by using autonomous psychological needs of self-determination theory and embracing Hofstede's framework in information and telecommunication technology (ICT) companies in Latvia.Design/methodology/approachA quantitative analysis of data from 271 employees and managers in Latvian ICT companies was used by applying structural equation modeling.FindingsThe result discloses that SL can promote IWB and KSB directly and through mediating effects of JA.Research limitations/implicationsThe research is constricted by geography and sample data representation from a specific sector. Hence, future studies can determine the gender effects, carry out more preventive measures to avoid common method bias between constructs, measure antecedents and the mediator before outcomes and examine JA as a moderator.Practical implicationsThe findings demonstrate that the Latvian ICT sector should recruit managers with SL potentials, train and equip managers with the required resources to implement SL practices properly and integrate JA across the organization to increase the manifestation of IWB and KSB.Originality/valueThis paper is the first to examine JA as the underlying process through which SL’s effects on IWB and KSB are explained in an individualistic country.
Analytical magnetic field calculation for flat permanent-magnet linear machines with dual-rotor by using improved two-dimensional hybrid analytical method
Authors: Ladghem Chikouche Brahim , Boughrara Kamel , Dubas Frédéric , Ibtiouen Rachid 
Published: July 2021

Purpose
This paper aims to propose an improved two-dimensional hybrid analytical method (HAM) in Cartesian coordinates, based on the exact subdomain technique and the magnetic equivalent circuit (MEC).

Design/methodology/approach
The magnetic field solution is obtained by coupling an exact analytical model (AM), calculated in all regions having relative permeability equal to unity, with a MEC, using a nodal-mesh formulation (i.e. Kirchhoff’s current law) in ferromagnetic regions. The AM and MEC are connected in both axes (x, y) of the (non-)periodicity direction (i.e. in the interface between the tooth regions and all its adjacent regions as slots and/or air-gap). To provide accuracy solutions, the current density distribution in slot regions is modeled by using Maxwell’s equations instead of the MEC characterized by an equivalent magnetomotive force (MMF) located in slots, teeth and yokes.

Findings
It is found that whatever the iron core relative permeability, the developed HAM gives accurate results for no- and on-load conditions. The finite-element analysis demonstrates excellent results of the developed technique.

Originality/value
The main objective of this paper is to make a direct coupling between the AM and MEC in both directions (i.e. x- and y-edges). The current density distribution is modeled by using Maxwell’s equations instead of the MEC and characterized by an MMF.
Green maintainability assessment of building-integrated photovoltaic (BIPV) applications: lessons learnt
Authors: Conejos Sheila , Chew Michael Y.L. , Tay Karlyn , Tay Stephen , Safiena Sufiana 
Published: July 2021

PurposeThe maintenance of green building technologies such as building-integrated photovoltaic (BIPV) is a challenge due to the non-existence of maintainability considerations during the design stage. This led to building defects which accounts to high expenditures throughout the building's lifecycle. The use of BIPV in buildings is an emergent trend, and further research is requisite for their maintainability. This paper assesses the performance and maintainability of BIPV façade applications based on the green maintainability design considerations.Design/methodology/approachQualitative method is undertaken in this study, which includes field surveys, instrumental case studies and stakeholder interviews to probe the issues linked with the BIPV's maintainability.FindingsFindings have shown some technical defects discovered in BIPV applications in tropical areas, as well as issues on cost, aesthetics and implementation are the main causes for the low adoption of BIPV in Singapore.Originality/valueUnderstanding the research outcomes will embolden designers and allied professionals to team up in ensuring the long-term maintainability and sustainability of green building technologies. This research gives recent and important information in the design, installation and maintainability of BIPV, as well as good practices that would add value to facilities management and to the design of green building technologies.
Foreign ownership, state ownership and cash holdings under the global financial crisis: evidence from the emerging market of Vietnam
Authors: Nguyen Thi Quynh Nga , Tran Quoc Trung , Doan Hong Phat 
Published: July 2021

PurposeThis paper investigates how the global financial crisis changes the effects of state ownership and foreign ownership on corporate cash holdings in an emerging market.Design/methodology/approachWe employ an interactive term between state ownership (foreign ownership) and a crisis dummy to analyze how the global financial crisis determines the effect of state ownership (foreign ownership) on corporate cash holdings.FindingsWith a research sample including 5,493 observations from 621 listed firms over the period 2007–2017, we find that state ownership (foreign ownership) is negatively (positively) related to corporate cash holdings and the effect of state ownership (foreign ownership) is stronger (weaker) during the crisis period. Moreover, the increase in the effect of state ownership is larger in financially unconstrained firms.Originality/valuePrior research shows that the effects of state ownership and foreign ownership on corporate cash holdings in emerging markets are still debatable. This paper extends this line of research by investigating how the global financial crisis – an exogenous shock – changes these effects.
Transnational universities, host communities and local residents: social impacts, university social responsibility and campus sustainability
Authors: Chen Chen , Vanclay Frank 
Published: July 2021

Purpose
This paper aims to discuss how transnational universities create negative and positive social impacts on their host communities and what this means for campus sustainability and the expectation that universities contribute to sustainable development and to their local communities.

Design/methodology/approach
Using mixed methods, a multiple case study approach and qualitative meta-analysis, this study considers six transnational university campuses in China in terms of their relationship with local communities.

Findings
Because of the good reputation of universities generally, local residents tended to accord a social licence to operate (i.e. approval) to new university campuses. However, universities generally do not manage their social impacts, as well as many other industries and generally fail to consider the corporate social responsibility issues and the environmental, social and governance aspects of their activities. To improve their social licence to operate and grow and to meet expectations around “university social responsibility”, campus developments should observe key international principles and human rights standards: full disclosure of information; effective community engagement; appropriate resettlement and livelihood restoration; effective harm reduction procedures; provision of local benefits (benefit sharing); monitoring and adaptive management and implement a grievance redress mechanism.

Originality/value
This paper encourages broader thinking about sustainability in a higher education context and about what university social responsibility entails. Specifically, this study argues that the relationship between universities and their host communities also needs to be considered, especially during campus construction.
Innovation in the “forgotten businesses”
Authors: Silva Glessia , Di Serio Luiz Carlos 
Published: July 2021

PurposeThe objective of this article is to discuss how the research on innovation in the small businesses may be operationalized. This paper discusses the field's concepts, typologies, units of analysis and the general basic assumptions pertaining to the operationalization of innovation research in small businesses.Design/methodology/approachThe article is an essay, whose format aims to provide the reader with reflections and multiple questions, by instigating the free thinking, the research as well as the construction of different ideas and/or perceptions in a logical and scientific way (Meneghetti, 2011). Thus, a conceptual approach for the operationalization of the innovation research in small businesses is proposed and discussed.FindingsMost of the innovation literature has ignored the small businesses, so that its core concepts and basic assumptions should be reviewed in an inclusive approach. The authors developed an analytical proposal that consists of a four-step logical approach to researching innovation in small businesses, starting from the innovation's concept as something important and then evolving to discussing how one has to try and see the small business as an object of study.Originality/valueThe value of this paper lies with the attempt to critically bring the small businesses into the spotlight, as study them has practical and theoretical implications that go beyond the field of innovation itself.