bluuebunny/crossref_metadata_2025_split huggingface dataset:
MTH1 promotes mitotic progression to avoid oxidative DNA damage in cancer cells
Authors: Gad Helge , Mortusewicz Oliver , Rudd Sean G , Stolz Ailine , Amaral Nuno , Brautigham Lars , Pudelko Linda , Sanjiv Kumar , Kaldéren Christina , Jemth Ann-Sofie , Almlöf Ingrid , Visnes Torkild , Schultz Niklas , Boström Johan , Calderon Montano José Manuel , Hagenkort Anna , Groth Petra , Loseva Olga , Gokturk Camilla , Koolmeister Tobias , Wakchaure Prasad , Homan Evert , Ström Cecilia E , Scobie Martin , Bastians Holger , Berglund Ulrika Warpman , Helleday Thomas 
Published: March 2019

ABSTRACTBACKGROUNDWe developed MTH1 inhibitors (MTH1i) TH588 and TH1579 showing broad anti-cancer activity, while structurally distinct MTH1i fail to kill cancer cells. Here, we describe a new role of MTH1 in mitosis and the detailed mechanism of action of TH1579 (karonudib) and other structurally distinct MTH1i.MATERIALS AND METHODSCancer cell lines or zebrafish embryos were treated with MTH1i or siRNA targeting MTH1 and analysed primarily by live cell and immunofluorescence microscopy, survival assays, DNA fibre or COMET assays. MTH1 and tubulin interactions were analysedin vitrousing co-immunoprecipitation and tubulin polymerisation assays.RESULTSHere, we describe a mitotic role for the MTH1 protein, which binds to tubulin, is required for microtubule polymerisation, correct spindle assembly, mitosis progression and suppression reactive oxygen species (ROS) generation in mitosis. Potent MTH1i display differential abilities to break the MTH1-tubulin interaction and cause mitotic arrest, demonstrating 8-oxodGTPase and mitotic function of MTH1 are mechanistically distinct. TH588 and TH1579 have more profound effect on mitotic arrest than other MTH1i explained by additional direct inhibition of tubulin polymerisation. MTH1i only inhibiting 8-oxodGTPase activity synergize with mitotic poisons.CONCLUSIONSEfficient MTH1 have a dual mechanism of action: inhibiting mitosis (to generate ROS) and promoting 8-oxodGTP incorporation into DNA during mitotic replication, dependent on ROS generation. Direct inhibition of tubulin polymerisation of TH588 and TH1579 increase their ability to arrest cells and generate ROS in mitosis. Furthermore, non-cytotoxic MTH1 can become effective and increase incorporation of oxidised nucleotides into DNA when combined with sub-therapeutic concentrations of mitotic inhibitors or challenged directly by 8-oxodGTP.
XPO1 gene therapy restores cardiac function in rats with chronic induced myocardial infarction
Authors: García-Manzanares María , Gil-Cayuela Carolina , Martínez-Dolz Luis , González-Juanatey José Ramón , Lago Francisca , Portolés Manuel , Roselló-Lletí Esther , Rivera Miguel 
Published: March 2019

AbstractBackgroundIn previous studies, we showed that several nuclear-cytoplasmic transport molecules were closely related to ventricular dysfunction in human heart failure. Particularly, the transcriptomic signature of XPO1 was highly expressed and inversely related to left ventricular function in heart failure patients of ischemic etiology. Therefore, we hypothesized that in a rat model of myocardial infarction treated with AAV9-shXPO1, an improvement in the ventricular function after a follow-up period may be observed.MethodsWe induced myocardial infarction by coronary ligation in Sprague-Dawley rats (n=10), five of them received AAV9-shXPO1 treatment after four months and the other five infarcted rats did not receive any treatment. For non-failing controls, healthy Sham rats (n=5) received the placebo AAV9-scramble. Serial echocardiographic assessment was performed before, as well as, two and five months after intravenous injection.ResultsAAV9-shXPO1-treated rats showed improved fractional shortening (16.8 ± 2.8 vs 24.6 ± 4.1%, P<0.05) and LV systolic (5.10 ± 0.79 vs 3.52 ± 0.88mm, P<0.05) and diastolic (6.17 ± 0.95 vs 4.70 ± 0.93mm, P<0.05) diameters when comparing measurements obtained before and five months after AAV9 injection. We did not observe this improvement in untreated infarcted rats. Furthermore, EXP-1 levels in rats heart, brain, skeletal muscle, and liver were determined by western-blot and compared to controls in AAV9-shXPO1-treated rats. Lower levels of EXP-1 in cardiac tissue were observed (P<0.05).DiscussionAt five months follow-up, ischemic AAV9-shXPO1-treated rats showed partial recovery of LV myocardial function. No secondary symptoms attributable to AAV9-shXPO1 were observed in skeletal muscle, liver and brain.
Flow arrest in the plasma membrane
Authors: Chein Michael , Perlson Eran , Roichman Yael 
Published: March 2019

AbstractThe arrangement of receptors in the plasma membrane strongly affects the ability of a cell to sense its environment both in terms of sensitivity and in terms of spatial resolution. The spatial and temporal arrangement of the receptors is affected in turn by the mechanical properties and the structure of the cell membrane. Here we focus on characterizing the flow of the membrane in response to the motion of a protein embedded in it. We do so by measuring the correlated diffusion of extracellularly tagged transmembrane neurotrophin receptors TrkB and p75 on transfected neuronal cells. In accord with previous reports, we find that the motion of single receptors exhibits transient confinement to sub-micron domains. We confirm predictions based on hydrodynamics of fluid membranes, finding long-range correlations in the motion of the receptors in the plasma membrane. However, we discover that these correlations do not persist for long ranges, as predicted, but decay exponentially, with a typical decay length on the scale of the average confining domain size.
CNEr: a toolkit for exploring extreme noncoding conservation
Authors: Tan Ge , Polychronopoulos Dimitris , Lenhard Boris 
Published: March 2019

AbstractConserved Noncoding Elements (CNEs) are elements exhibiting extreme noncoding conservation in Metazoan genomes. They cluster around developmental genes and act as long-range enhancers, yet nothing that we know about their function explains the observed conservation levels. Clusters of CNEs coincide with topologically associating domains (TADs), indicating ancient origins and stability of TAD locations. This has suggested further hypotheses about the still elusive origin of CNEs, and has provided a comparative genomics-based method of estimating the position of TADs around developmentally regulated genes in genomes where chromatin conformation capture data is missing. To enable researchers in gene regulation and chromatin biology to start deciphering this phenomenon, we developedCNEr, a R/Bioconductor toolkit for large-scale identification of CNEs and for studying their genomic properties. We applyCNErto two novel genome comparisons - fruit fly vs tsetse fly, and two sea urchin genomes - and report novel insights gained from their analysis. We also show how to reveal interesting characteristics of CNEs by coupling CNEr with existing Bioconductor packages.CNEris available at Bioconductor (https://bioconductor.org/packages/CNEr/) and maintained at github (https://github.com/ge11232002/CNEr).
FDM 3D printing method utility assessment in small RC aircraft design
Authors: Skawiński Igor , Goetzendorf-Grabowski Tomasz 
Published: March 2019

Purpose
The purpose of this paper is to investigate the possibility of manufacturing fused deposition modelling (FDM) 3D printed structures such as wings or fuselages for small remote control (RC) air craft and mini unmaned aerial vehicles (UAVs).

Design/methodology/approach
Material tests, design assumptions and calculations were verified by designing and manufacturing a small radio-controlled motor-glider using as many printed parts as possible and performing test flights.

Findings
It is possible to create an aircraft with good flight characteristics using FDM 3D printed parts. Current level of technology allows for reasonably fast manufacturing of 3D printed aircraft with good reliability and high success ratio of prints; however, only some of the materials are suitable for printing thin wall structures such as wings.

Practical implications
The paper proves that apart from currently popular small RC aircraft structural materials such as composites, wood and foam, there is also printed plastic. Moreover, 3D printing is highly competitive in some aspects such as first unit production time or production cost.

Originality/value
The presented manufacturing technique can be useful for quick and cost-effective creating scale prototypes of the aircraft for performing test flights.
The approximation method in the problem on a flow of viscous fluid around a thin plate
Authors: Berdnik Yanina , Beskopylny Alexey 
Published: March 2019

Purpose
The paper aims to obtain an effective solution to the problem on a flow of viscous fluid around a thin plate using a new approximation method based on the exact Navier–Stokes equations. Also, correction factors are proposed to improve the obtained solution at high Reynolds numbers.

Design/methodology/approach
The paper has opted for a method that is based on an approximation scheme for certain perturbations concerning the velocity of the oncoming unperturbed flow behind a leading edge of the plate as a zero approximation step. The perturbations are assumed to be small, far from the plate when compared to the basic flow to justify the linearization. Numerical methods are used for the integral equations at each approximation step.

Findings
This paper provides the friction force coefficient compared with the classical Blasius solution and the ANSYS results. Also, some diagrams of the velocity distribution in the flow are presented. The first and second approximation steps provide a sufficiently high degree of accuracy.

Research limitations/implications
Because of the chosen research approach, the results may lack accuracy for low and average Reynolds numbers. Thus, researchers are encouraged to improve the proposed method further.

Practical implications
The paper includes implications for the development of an aircraft design or a wind turbine design considering a wing as a thin plate at the first approximation.

Originality/value
This paper provides a new approximation method based on the exact Navier–Stokes equations, in contrast to the known solutions.
Perceived inequality and modes of political participation in South Korea
Authors: Lee Hyun Kyung , Kwon Hyeok Yong 
Published: March 2019

Purpose
The purpose of this paper is to explore whether and how the individual perceptions on income inequality and the inequality of opportunities affect two different modes of political participation, institutional and non-institutional, in South Korea.

Design/methodology/approach
The paper analyzes the Korean General Social Survey 2009 and 2014 and estimates logit and OLS models.

Findings
The authors find that neither the perceived inequality of income distribution nor the perceived inequality of opportunities affects the likelihood of individuals’ vote participation. The authors, however, find that the perceptions of inequality, both in terms of outcomes and opportunities affect citizens’ engagement in non-institutional forms of political participation.

Originality/value
This study provides a new discussion point about the political consequences of inequality in Korea. This paper distinguishes and analyzes the relative importance of perceived inequality of the outcomes and opportunities in democratic engagements. By considering various types of participation, institutional and non-institutional, this study contributes to deepen our understanding of the factors that drive citizens’ democratic political engagements.
Corporate entrepreneurship as a strategic approach for internal innovation performance
Authors: Tseng Cheng , Tseng Chien-Chi 
Published: March 2019

PurposeThe purpose of this paper is to explore corporate entrepreneurship and the relationship between intrapreneurship and the proposed strategic models through a literature review. This paper reviews the strategic approach for increasing internal innovation performance at corporations.Design/methodology/approachKey words were identified to use in the literature search: corporate entrepreneurship, innovation performance and entrepreneurial environment. Then, all of the several electronic databases available in the university’s electronic library, including Harvard Business Review and The University of Chicago Press, as well as journals, books, Google Scholar and other institutional resources.FindingsThe six innovative outcomes are motivating individuals to engage in innovative behavior, concentrating entrepreneurial ventures through a newly minted organization within a corporation, helping innovative-minded people to reach their full potential, rewarding a corporate entrepreneur, encouraging people to look at the organization from a broad perspective and educating employees about corporate entrepreneurship.Research limitations/implicationsThe study was exploratory, based on a literature review. Further studies are needed using empirical research to examine why corporate entrepreneurship was attributed to be the strategic approach for internal innovation performance.Practical implicationsBy implementing the strategic approaches, corporate management professionals can realize their entrepreneurial intentions for the firm and maintain their responsibility to shareholders in terms of other business and development goals.Originality/valueThe research constructs an input-process-output framework that minimizes external mergers and acquisitions and maximizes internal innovation performance. Value was created when corporate entrepreneurship was identified as a strategic approach for internal innovation performance.
What makes fashion consumers “click”? Generation of eWoM engagement in social media
Authors: Ananda Artha Sejati , Hernández-García Ángel , Acquila-Natale Emiliano , Lamberti Lucio 
Published: March 2019

PurposeThe purpose of this study is to investigate the perceived exposure of fashion consumers to different types of fashion brands’ social media marketing (SMM) actions in social media, and its relationship with the intention to engage in electronic word-of-mouth (eWoM) behaviors.Design/methodology/approachThe empirical study uses a survey conducted on a stratified random sample of 241 Indonesian members of fashion social media brand communities (SMBCs). The research design includes 19 types of SMM actions and 3 types of eWoM engagement behaviors, and investigates their relationship using point-biserial correlation.FindingsGeneration of intention to engage in “pass-on” and “endorsement” eWoM has different drivers and serves different purposes. The findings suggest that endorsement engagement is contingent on the consumer’s perceived exposure to marketing action stimuli, while pass-on engagement is driven by cognitive-inducing actions.Research limitations/implicationsThis study extends current theory on SMM strategy and its relationship with eWoM engagement with a theoretically grounded conceptualization of eWoM engagement behaviors through the use of one-click social plug-ins.Practical implicationsThe study offers guidelines for fashion brands to effectively design their SMM strategies by identifying specific drivers of consumers’ intention to engage in eWoM.Originality/valueThis study identifies sources of generation of eWoM engagement behavioral intention from a fine-grained analysis of marketing actions across various fashion SMBCs. Besides, it extends the applicability of the “mere exposure” effect to the SMM context. The research pioneers the study on fashion consumers’ eWoM engagement behaviors in Indonesia, a country with one of the largest social media populations.
The dimensionality of corporate communication management (CCM)
Authors: Mohamad Bahtiar , Nguyen Bang , Melewar TC , Gambetti Rossella 
Published: March 2019

PurposeThis paper aims to investigate the conceptualisation of corporate communication management (CCM) and its dimensionality from the practitioners’ perspectives. It proposes to validate an operational definition and dimensions of the CCM construct, which have not been identified in the literature.Design/methodology/approachThe initial concepts are based on academic literature and followed by 12 face-to-face interviews with corporate communication practitioners and consultants from Malaysia to confirm the practicality of each dimension. QSR Nvivo Version 9.0 software is used to analyse the qualitative data. Then, the data are classified through deductive content analysis based on key words or themes.FindingsThe diverse perspectives are shown from the practitioners and consultants on the dimensionality of CCM. Most of the interviewees suggest that CCM dimensions include corporate advertising, corporate affairs, investor relations and employee communication within the corporate communication and other departments. They also found the public relations and media relations are clearly under corporate communications manager’s supervision. This research confirms the concept of CCM and its dimensionality to operationalise the CCM construct. The CCM dimensions also offer opportunities for further research to develop the measurement scales.Originality/valueThis research contributes to the clarification on the subject matter by developing clear concepts of the CCM and by offering insights about the role of the CCM dimensions, which help managers to more successfully incorporate the CCM dimension into the corporate management strategy. This paper also examines the concept of CCM and confirms its dimensionality, which helps in developing the CCM measurement for further quantitative research.
Mathematical modelling and analysis of voltage super-lift power dc-dc converter for enhanced dynamic characteristics in CCM
Authors: R. Durga Devi , S. Nageswari 
Published: March 2019

Purpose
The purpose of this paper is to propose a mathematical model for voltage super-lift dc-dc power converter in continuous conduction mode (CCM). Using the presented mathematical model, the analysis of dynamics of power stage for voltage super-lift dc-dc power converter can be performed.

Design/methodology/approach
The proposed method is based on the average state space model using the state equations of the dc-dc power converter. In the proposed method, the converter is represented as a set of differential equations derived for each switching state of the power switch in terms of inductor current and capacitor voltage. The proposed method describes the dynamic behaviour of the system. The controller is designed to meet performance requirement of the system such as to maintain the dynamics such as stability, steady-state accuracy and the speed of response of the system. Using the obtained model, the analysis of dynamic response of the voltage super-lift dc-dc power converter can be performed.

Findings
The converter is modelled and verified using conventional circuit analysis method employing state-space averaging technique, and their corresponding transfer function is also derived. The dynamics of the converter is investigated using frequency response characteristics obtained using MATLAB programming environment. In addition, to improve the stability of the converter, proportional-integral controller is designed using Ziegler–Nichols tuning rules, and the effect of the compensator in the plant is also investigated.

Originality/value
The proposed method can be used for analysing the dynamics of power stage for voltage super-lift DC-DC power converter.
User centric facility maintenance model for public housing
Authors: S. Gopikrishnan , Kumar Virendra 
Published: March 2019

Purpose
The purpose of this study is to develop a user-centric facility maintenance model through user satisfaction index linked intervention strategies for public housing.

Design/methodology/approach
User requirements are standardized by ISO 6241-1984(E), building performance attributes (BPAs) influencing those user requirements are identified. Selected BPAs are amplified as sub attributes characterizing BPAs. Grouping of BPAs are done to suit established hierarchy of government facility maintenance (FM) agencies. Post validation of BPAs/sub attributes for adequacy, they are ranked and weights assigned through expert survey. Questionnaire designed to garner user feedback based on BPAs and sub attributes to develop a user satisfaction index (USI) that can enable quantification of user feedback. A theoretical framework for interventions is designed which can be enmeshed in existing hierarchy of FM agencies.

Findings
84 per cent of expert survey group comprising architects/planners/engineers/facility managers/consultants agreed on adequacy of attributes and 78 per cent endorsed necessity for amplification of BPAs through sub attributes. USI shall facilitate comparison of pre- and post-implementation of interventions. A theoretical framework for FM agencies is developed for interventions.

Research limitations/implications
The FM model presently is limited to application only in public housing. For wider application to other built facilities, choice of BPAs need to made accordingly. As the implementation of interventions and its comparison is likely to take at least a financial year, the theoretical framework can be validated subsequently as a future scope of research.

Practical implications
The biggest implication of this FM model is that the most important stakeholder, that is, end user/occupant gets to register feedback on building performance. This model establishes accountability of government FM agencies and also validates the methods and processes adopted for maintenance of built facilities.

Social implications
A section of the feedback comprises issues not directly related building envelope but societal issues. This feedback in the long run can become a repertoire of data for administrative agencies to map changing aspirations of government employees with respect to authorization/entitlements.

Originality/value
Quantification of user satisfaction is an inevitable necessity in spite of being a qualitative aspect. This study makes a unique attempt to provide a framework to establish accountability of government FM agencies which is presently non-existent.