bluuebunny/crossref_metadata_2025_split huggingface dataset:
BRD4 inhibitors block telomere elongation
Authors: Wang Steven , Pike Alexandra M. , Lee Stella S. , Connelly Carla J. , Greider Carol W. 
Published: February 2017

ABSTRACTCancer cells maintain telomere length equilibrium to avoid senescence and apoptosis induced by short telomeres, which are triggered by the DNA damage response. Limiting the potential for telomere maintenance in cancer cells has been long been proposed as a therapeutic target. Using an unbiased shRNA screen targeting known kinases, we identified bromodomain 4 (BRD4) as a telomere length regulator. Four independent BRD4 inhibitors blocked telomere elongation, in a dose dependent manner, in mouse cells overexpressing telomerase. Long-term treatment with BRD4 inhibitors caused telomere shortening in both mouse and human cells, suggesting BRD4 plays a role in telomere maintenancein vivo. Telomerase enzymatic activity was not directly affected by BRD4 inhibition. BRD4 is in clinical trials for a number of cancers, but its effects on telomere maintenance have not been previously reported investigated.
Comparative genomics approaches accurately predict deleterious variants in plants
Authors: Kono Thomas J. Y. , Lei Li , Shih Ching-Hua , Hoffman Paul J. , Morrell Peter L. , Fay Justin C. 
Published: February 2017

AbstractRecent advances in genome resequencing have led to increased interest in prediction of the functional consequences of genetic variants. Variants at phylogenetically conserved sites are of particular interest, because they are more likely than variants at phylogenetically variable sites to have deleterious effects on fitness and contribute to phenotypic variation. Numerous comparative genomic approaches have been developed to predict deleterious variants, but the approaches are nearly always assessed based on their ability to identify known disease-causing mutations in humans. Determining the accuracy of deleterious variant predictions in nonhuman species is important to understanding evolution, domestication, and potentially to improving crop quality and yield. To examine our ability to predict deleterious variants in plants we generated a curated database of 2,910Arabidopsis thalianamutants with known phenotypes. We evaluated seven approaches and found that while all performed well, their relative ranking differed from prior benchmarks in humans. We conclude that deleterious mutations can be reliably predicted inA. thalianaand likely other plant species, but that the relative performance of various approaches does not necessarily translate from one species to another.
Technological innovation among internationality active SMEs in the Czech economy
Authors: Wadhwa Preeti , McCormick Marleen , Musteen Martina 
Published: February 2017

PurposeThis paper aims to examine the impact of human and social capital of CEOs of internationally active small- and medium-sized enterprises (SMEs) in the Czech Republic on their firms’ approach to technological innovation.Design/methodology/approachThe study sample was drawn from data collected from the population of Czech manufacturing firms. The final sample included 153 SMEs that met the criteria for inclusion in the study. The authors employed robust regression analysis to test their specific hypotheses.FindingsThis study found that human capital (in the form of CEOs’ professional background and foreign customer knowledge) and social capital (conceptualized as embeddedness in the international markets) of CEOs in the Czech Republic impacted their firms’ approach to technological innovation. Specifically, firms headed by CEOs with professional background in output functions (R&D and marketing) are more likely to invest in technological innovation. The same was found true for firms led by CEOs who possessed a strong knowledge of international customers and were socially embedded in international markets.Originality/valueThis study makes a twofold contribution to the extant literature. First, it develops and tests the theoretical link between human and social capital and technological innovation among internationally active firms. Second, it highlights factors that positively influence technological innovation in the context of a small Central European economy, a setting that has been generally viewed as unfavorable to such innovation.
Editing JAT and enabling publication: an afterword
Authors: Abbott Chris 
Published: February 2017

Purpose
An afterword from the previous editor of this journal, looking back at what has been notable and ahead to what seem to be likely changes in the future. The paper aims to discuss this issue.

Design/methodology/approach
Overview of key issues in the first ten years of the Journal of Assistive Technologies.

Findings
Some key issues are identified and likely future foci are tentatively suggested.

Originality/value
An editorial perspective.
Corporate hedging, firm focus and firm size: the case of REITs
Authors: Wei Peihwang , Xu Li , Zeng Bei 
Published: February 2017

PurposeThe purpose of this paper is to investigate the substitutability of corporate hedging and diversification in the real estate investment trusts (REITs) industry. The authors hypothesize that, relative to diversified firms, focused firms are more likely to be associated with hedging. The role of firm size is also analyzed.Design/methodology/approachThe logistic regression approach is utilized to analyze the probability of hedging and the panel regression approach is used to examine the amount of hedging.FindingsThe authors find that, relative to diversified firms, firms focused on a single property type are more likely to engage in hedging. However, this finding is significant only for smaller firms, which implies a non-linear relation between hedging and firm size. The evidence is not as strong when firm focus is measured by geographic concentration. In terms of hedging amount, smaller firms’ average hedge ratio is greater than that of larger firms. For either small or large firms group, hedging amounts increase with firm focus measured by either property or geographic concentration and increase with firm sizes.Research limitations/implicationsThe results imply that, relative to diversified REITs, REITs focused on a single property type are more likely to engage in hedging. However, this finding is significant only for smaller firms, which implies a non-linear relation between hedging and firm size. The evidence is not as strong when firm focus is measured by geographic concentration, suggesting that geographic concentration is perceived to be less risky than property type concentration. For either small or large firms group, hedging amounts increase with firm focus measured by either property or geographic concentration and increase with firm sizes, which implies that hedging amount does not depend on firm size. The sample period is limited to the years 2010 to 2013 because some data needs to be manually collected.Practical implicationsThe results imply that REITs consider both property diversification and hedging in managing their risk.Originality/valueThe research represents an early attempt to investigate the relation between corporate hedging and diversification. The investigation into the REIT industry has several advantages such as a lower likelihood of using derivatives for speculation.
Towards reconnecting: creative formulation and understanding dissociation
Authors: Parry Sarah L. , Lloyd Mike 
Published: February 2017

Purpose
The term dissociation can describe a coping strategy to protect oneself against something unwanted in the moment, a disconnection from sensations and experiences in the here and now. Although the more severe experiences of dissociation have been the subject of intense study over the last two decades, much less has been written about clients commonly seen in mental health services with mild to moderate dissociative conditions. Specifically, the purpose of this paper is to attend to therapeutic work with a client who experienced moderate dissociation, which caused disruptions to her autobiographical narrative and sense-of-self.

Design/methodology/approach
This single case design details the therapeutic journey of a Caucasian woman in her early 40s, who experienced moderate dissociation. The report illustrates how the process of creative artwork formulation helped address unwanted dissociative experiences whilst enhancing other coping strategies.

Findings
The client’s personal resources combined with a creative and responsive approach to formulation and reformulation facilitated the process of reconnecting with herself and others through developing awareness of her strengths and past means of coping, finally developing a consistent self-narrative.

Practical implications
The experiences of a creative approach to formulation are discussed in relation to the client’s past traumas and case relevant theory. These preliminary findings suggest creative artwork formulation is an effective tool in terms of developing trust and shared understanding within the therapeutic relationship and meaning making processes throughout therapy.

Originality/value
This case study presents an account of creative artwork formulation used as a method of formulation and reformulation specifically with a client experiencing moderate dissociative experiences following interpersonal traumas. Further, the report discusses the ways in which creative artwork formulation facilitated memory exploration and integration, as well as containing meaning making and healing.
A community hub approach to older people’s housing
Authors: Evans Simon , Atkinson Teresa , Darton Robin , Cameron Ailsa , Netten Ann , Smith Randall , Porteus Jeremy 
Published: February 2017

Purpose
The purpose of this paper is to explore the potential of housing with care schemes to act as community hubs. The analysis highlights a range of benefits, barriers and facilitators.

Design/methodology/approach
Data are presented from the Adult Social Services Environments and Settings project which used a mixed methods approach including a review of the literature, surveys and in-depth case study interviews.

Findings
Most housing with care schemes have a restaurant or café, communal lounge, garden, hairdresser, activity room and laundrette, while many also have a library, gym, computer access and a shop. Many of these facilities are open not just to residents but also to the wider community, reflecting a more integrated approach to community health and adult social care, by sharing access to primary health care and social services between people living in the scheme and those living nearby. Potential benefits of this approach include the integration of older people’s housing, reduced isolation and increased cost effectiveness of local services through economies of scale and by maximising preventative approaches to health and wellbeing. Successful implementation of the model depends on a range of criteria including being located within or close to a residential area and having on-site facilities that are accessible to the public.

Originality/value
This paper is part of a very new literature on community hub models of housing with care in the UK. In the light of new requirements under the Care Act to better coordinate community services, it provides insights into how this approach can work and offers an analysis of the benefits and challenges that will be of interest to commissioners and providers as well as planners. This was a small scale research project based on four case studies. Caution should be taken when considering the findings in different settings.
Corporate citizenship and social responsibility policies in the United States of America
Authors: Camilleri Mark Anthony 
Published: February 2017

PurposeThe aim of this case study is to outline relevant regulatory guidelines on environmental, social and governance issues in the USA. This contribution includes a thorough analysis of several institutional frameworks and guiding principles that have been purposely developed to foster corporate citizenship behaviours.Design/methodology/approachA case study methodology involved a broad analysis of US regulatory policies, voluntary instruments and soft laws that have stimulated organisations to implement and report their responsible behaviours.FindingsThis contribution ties the corporate citizenship behaviours with the institutional and stakeholder theories. The case study evaluated the US’s federal government, bureaus and its agencies’ policies on human rights, health and social welfare, responsible supply chain and procurement of resources, anticorruption, bribery and fraudulent behaviours, energy and water conservation practices as well as environmental protection, among other issues.Research limitations/implicationsPast research may have not sufficiently linked corporate citizenship with the corporate social responsibility (CSR) paradigm. This research reports how different US regulatory institutions and non-governmental organisations are pushing forward the social responsibility, environmental sustainability as well as the responsible corporate governance agenda.Originality/valueThis research critically analyses US policy and regulatory instruments including relevant legislation and executive orders that are primarily intended to unlock corporate citizenship practices from business and industry. It has also provided a conceptual framework for the corporate citizenship notion. In conclusion, it implies that there are business and political cases for corporate citizenship.
Controlling volatility but not growth: firms’ strategic orientations
Authors: Batra Safal 
Published: February 2017

Purpose
While a lot is known about organizational growth, little is understood about how to manage volatility that comes along with growth. This paper, using existing research in this area and the empirical findings of a study by Moreno et al. (2014), offers crucial insights about managing volatility for firms trying to grow at the pace of technological changes. An attempt is made to highlight the differences of growth and volatility in a language that is easily comprehensible to practitioners.

Design/methodology/approach
The paper is based on existing literature in the area of growth and on author’s personal interactions with the founders of small firms.

Findings
In this paper, it is argued that firm’s strategic orientations can be used as a contingency of growth–volatility relationship. In other words, firms with a strong entrepreneurial and market orientation are positioned to benefit from the pursuit of growth while still keeping the issues of volatility in control.

Practical implications
By clearly elucidating the concept of volatility and growth, the paper helps practitioners in finding ways of benefiting from growth and controlling unnecessary volatility.

Originality/value
This paper is among the limited research attempts addressing the concept of volatility. The finding that growth and volatility are inter-linked but different can be used effectively by practitioners.
Why a buyer is much more than a cost-killer
Authors: Poissonnier Hugues 
Published: February 2017

PurposeThis paper aims to show the evolutions of the missions given to buyers.Design/methodology/approachThis study uses a historical approach.FindingsCost-killing is less and less the more important part of the buyer’s job.Originality/valueThis paper is aimed at showing the importance of alternative missions given to buyers, in addition to the traditional mission consisting in reducing costs. More and more supply security and value creation are considered as more strategic missions for purchasing.
Maximising evolutionary potential in functional proxies for extinct species: a conservation genetic perspective on de‐extinction
Authors: Steeves Tammy E. , Johnson Jeff A. , Hale Marie L. 
Published: February 2017

Summary

De‐extinction sensu stricto is the resurrection of phenotypic traits once possessed by extinct species to create extant functional proxies. To realise the ecological benefit of de‐extinction, self‐sustaining (genetically viable) populations of functional proxies are required.

It is often implied, yet rarely stated, that the genetic challenges associated with the survival and recovery of extant threatened species in an effort to conserve biodiversity are also relevant to the use of functional proxies of extinct species as a conversation tool.

Here, we highlight the importance of prioritising evolutionary potential − the capacity to evolve (adapt) in response to environmental change − in populations of functional proxies.

We use conservation genetic principles to describe impediments to the creation and maintenance of evolutionary potential as a series of potentially unavoidable genetic bottlenecks (pre‐extinction, resurrection, captive, translocation).

To give any successfully translocated populations of functional proxies the best chance to survive beyond the first few generations in the wild, we advocate the use of a holistic framework that includes the creation of sufficiently large, genetically diverse populations that harbour the ability to adapt to a changing environment.

A lay summary is available for this article.
Student peer teaching in paediatric simulation training is a feasible low‐cost alternative for education
Authors: Wagner Michael , Mileder Lukas P. , Goeral Katharina , Klebermass‐Schrehof Katrin , Cardona Francesco S. , Berger Angelika , Schmölzer Georg M. , Olischar Monika 
Published: February 2017

AbstractAimThe World Health Organization recommends regular simulation training to prevent adverse healthcare events. We used specially trained medical students to provide paediatric simulation training to their peers and assessed feasibility, cost and confidence of students who attended the courses.MethodsStudents at the Medical University of Vienna, Austria were eligible to participate. Students attended two high‐fidelity simulation training sessions, delivered by peers, which were videorecorded for evaluation. The attendees then completed questionnaires before and after the training. Associated costs and potential benefits were analysed.ResultsFrom May 2013 to June 2015, 152 students attended the sessions and 57 (37.5%) completed both questionnaires. Satisfaction was high, with 95% stating their peer tutor was competent and 90% saying that peer tutors were well prepared. The attendees’ confidence in treating critically ill children significantly improved after training (p < 0.001). The average costs for a peer tutor were six Euros per working hour, compared to 35 Euros for a physician.ConclusionUsing peer tutors for paediatric simulation training was a feasible and low‐cost option that increased the number of medical students who could be trained and increased the self‐confidence of the attendees. Satisfaction with the peer tutors was high.
WNT signalling events near the cell membrane and their pharmacological targeting for the treatment of cancer
Authors: Driehuis Else , Clevers Hans 
Published: February 2017

WNT signalling is an essential signalling pathway for all multicellular animals. Although first described more than 30 years ago, new components and regulators of the pathway are still being discovered. Considering its importance in both embryonic development and adult homeostasis, it is not surprising that this pathway is often deregulated in human diseases such as cancer. Recently, it became clear that in addition to cytoplasmic components such as β‐catenin, other, membrane‐bound or extracellular, components of the WNT pathway are also altered in cancer. This review gives an overview of the recent discoveries on WNT signalling events near the cell membrane. Furthermore, membrane‐associated components of the WNT pathway, which are more accessible for therapeutic intervention, as well therapeutic approaches that already target those components will be discussed. In this way, we hope to stimulate the development of effective anti‐cancer therapies that target this fascinating pathway.Linked ArticlesThis article is part of a themed section on WNT Signalling: Mechanisms and Therapeutic Opportunities. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.24/issuetoc
Regulatory effects of bone morphogenetic protein‐4 on tumour necrosis factor‐α‐suppressed Runx2 and osteoprotegerin expression in cementoblasts
Authors: Wang Yunlong , He Hong , Cao Zhengguo , Fang Yi , Du Mingyuan , Liu Zhijian 
Published: February 2017

AbstractObjectivesRoot resorption is a common phenomenon presented in periodontitis and orthodontic treatment, both of which are accompanied by an elevated TNF‐α expression level in the periodontal tissues. Previously, we proved that TNF‐α showed an inhibitory effect on cementoblast differentiation, mineralization and proliferation. However, the effect of TNF‐α on Runx2 and osteoprotegerin (OPG) expression remains undetermined. This study aimed to identify the influence of TNF‐α on Runx2 and OPG expression in cementoblasts and to test whether BMP‐2,‐4,‐6,‐7 would affect TNF‐α‐regulated Runx2 and OPG.Materials and methodsAn immortalized murine cementoblast cell line OCCM‐30 was used in this study. The expression of Runx2 and OPG were examined by qRT‐PCR after stimulating cells with TNF‐α. The role of signalling pathways, including MAPK, PI3K‐Akt and NF‐κB, were studied with the use of specific inhibitors. Cells were treated with TNF‐α in combination with BMP‐2,‐4,‐6 or ‐7, then the expression of Runx2 and OPG, the activity of MAPK and NF‐κB pathways, and the proliferation ability were evaluated by qRT‐PCR, Western blot and MTS assay respectively.ResultsTNF‐α inhibited Runx2 and OPG mRNAs in OCCM‐30 cells, and the inhibitory effects were further aggravated by blocking p38 MAPK or NF‐κB pathway. TNF‐α‐inhibited Runx2 and OPG were up‐regulated by BMP‐4. The p38 MAPK and Erk1/2 pathways were further activated by the combined treatment of BMP‐4 and TNF‐α compared with TNF‐α alone. Finally, the TNF‐α‐suppressed proliferation was not obviously affected by BMP‐2,‐4,‐6 or ‐7.ConclusionsTNF‐α inhibited Runx2 and OPG in cementoblasts, and the p38 MAPK and NF‐κB pathways acted in a negative‐feedback way to attenuate the inhibitory effects. TNF‐α‐inhibited Runx2 and OPG could be effectively up‐regulated by BMP‐4; however, further investigations are needed to fully elaborate the underlying mechanisms.