bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prostaglandin EP3 Receptor signaling is required to prevent insulin hypersecretion and metabolic dysfunction in a non-obese mouse model of insulin resistance
Authors: Wisinski Jaclyn A. , Reuter Austin , Peter Darby C. , Schaid Michael D. , Fenske Rachel J. , Kimple Michelle E. 
Published: June 2019

AbstractWhen homozygous for theLeptinObmutation (Ob), Black-and-Tan Brachyury (BTBR) mice become morbidly obese and severely insulin resistant, and by 10 weeks of age, frankly diabetic. Previous work has shown Prostaglandin EP3 Receptor (EP3) expression and activity is up-regulated in islets from BTBR-Ob mice as compared to lean controls, actively contributing to their beta-cell dysfunction. In this work, we aimed to test the impact of beta-cell-specific EP3 loss on the BTBR-Ob phenotype by crossingPtger3floxed mice with the Rat insulin promoter (RIP)-CreHerrdriver strain. Instead, germline recombination of the floxed allele in the founder mouse – an event whose prevalence we identified as directly associated with underlying insulin resistance of the background strain – generated a full-body knockout. Full-body EP3 loss provided no diabetes protection to BTBR-Ob mice, but, unexpectedly, significantly worsened BTBR-lean insulin resistance and glucose tolerance. Thisin vivophenotype was not associated with changes in beta-cell fractional area or markers of beta-cell replicationex vivo. Instead, EP3-null BTBR-lean islets had essentially uncontrolled insulin hypersecretion. The selective up-regulation of constitutively-active EP3 splice variants in islets from young, lean BTBR mice as compared to C57BL/6J, where no phenotype of EP3 loss has been observed, provides a potential explanation for the hypersecretion phenotype. In support of this, high islet EP3 expression in Balb/c females vs. Balb/c males was fully consistent with their sexually-dimorphic metabolic phenotype after loss of EP3-coupled Gαzprotein. Taken together, our findings provide a new dimension to the understanding of EP3 as a critical brake on insulin secretion.New and NoteworthyIslet Prostaglandin EP3 receptor (EP3) signaling is well-known as up-regulated in the pathophysiological conditions of type 2 diabetes, contributing to beta-cell dysfunction. Unexpected findings in mouse models of non-obese insulin sensitivity and resistance provide a new dimension to our understanding of EP3 as a key modulator of insulin secretion. A previously-unknown relationship between mouse insulin resistance and the penetrance of Rat insulin promoter-driven germline floxed allele recombination is critical to consider when creating beta-cell-specific knockouts.For Table of Contents Use Only
Novel Quinazoline derivatives inhibited HCV Serine protease and viral replication in Huh-7 cells
Authors: Rothan Hussin A. , Faraj Fadhil Lafta , Teoh Teow Chong , Yusof Rohana 
Published: June 2019

AbstractDrugs against HCV infection are facing several drawbacks such as undesirable side effects, emerging of HCV resistant strains, and high cost of the entire course of treatment. Thus, new active and cost-effective compounds are required to develop effective drugs to combat HCV infection. This study was designed to test the antiviral activity of quinazoline derivatives against HCV infection using HCV protease assay (HCV NS3-4Apro) and cell-based HCV replicon assay. The results showed that some of quinazoline derivatives inhibited HCV NS3-4Apro with IC50 ranged from 42 µM of compound 4 to 150 µM of compound 2. In this study, compound 4 was considered as the best compound lead to developing potent anti-HCV NS3-4Apro inhibitors. The toxic dose of compound 4 was more than 80 µM for 24, 48, and 72 h. Compound 4 showed dose-dependent inhibition against HCV replication with a considerable reduction in Rluc activity at 40 µM. This finding was further investigated by immunostaining that showed the inhibitory effect of compound 4 against HCV NS3-4Apro was dose-dependent. This study identified a unique small molecule compound that could lead to the development of HCV NS3-A4pro inhibitors and would be useful to develop highly effective drugs for HCV infection based on HCV NS3-4A protease inhibition.
Foot strike pattern during running alters muscle-tendon dynamics of the gastrocnemius and the soleus
Authors: Yong Jennifer R. , Dembia Christopher L. , Silder Amy , Jackson Rachel W. , Fredericson Michael , Delp Scott L. 
Published: June 2019

ABSTRACTRunning is thought to be an efficient gait due, in part, to the behavior of the plantar flexor muscles and the elastic energy storage in the Achilles tendon. Although plantar flexor muscle mechanics and Achilles tendon energy storage have been explored during rearfoot striking, they have not been fully characterized during forefoot striking. This study examines how plantar flexor muscle-tendon mechanics during running differ between rearfoot and forefoot striking. We used musculoskeletal simulations, driven by joint angles and electromyography recorded from runners using both rearfoot and forefoot striking running patterns, to characterize plantar flexor muscle-tendon mechanics. The simulations revealed that foot strike pattern affected the soleus and gastrocnemius differently. For the soleus, forefoot striking resulted in decreased tendon energy storage and decreased positive fiber work compared to rearfoot striking. For the gastrocnemius, forefoot striking resulted in greater activation and increased negative fiber work compared to rearfoot striking. The increased activation and negative fiber work in the gastrocnemius during forefoot striking suggest that runners planning to convert to forefoot striking would benefit from a progressive eccentric gastrocnemius strengthening program to avoid injury.
The HSV-1 immediate early protein ICP22 is a J-like protein required for Hsc70 reorganization during lytic infection
Authors: Adlakha Mitali , Livingston Christine M. , Bezsonova Irina , Weller Sandra K. 
Published: June 2019

ABSTRACTMolecular chaperones and co-chaperones are the most abundant cellular effectors of protein homeostasis, assisting protein folding and preventing aggregation of misfolded proteins. We have previously shown that HSV-1 infection results in the drastic spatial reorganization of the cellular chaperone Hsc70 into nuclear domains called VICE (VirusInducedChaperoneEnriched) domains and that this recruitment is dependent on the viral immediate early protein ICP22. In this paper, we present several lines of evidence supporting the notion that ICP22 functions as a virally encoded co-chaperone (J-protein/Hsp40) functioning together with its Hsc70 partner to recognize and manage aggregated and misfolded proteins. We show that ICP22 results in (i) nuclear sequestration of non-native proteins, (ii) reduction of cytoplasmic aggresomes in cells expressing aggregation-prone proteins and (iii) thermoprotection against heat-inactivation of firefly luciferase. (iv) Sequence homology analysis indicated that ICP22 contains an N-terminal J-domain and a C-terminal substrate binding domain, similar to type II cellular J-proteins. ICP22 may, thus, be functionally similar to J-protein/Hsp40 co-chaperones that function together with their HSP70 partners to prevent aggregation of non-native proteins. This is not the first example of a virus hijacking a function of a cellular chaperone, as SV40 T Antigen was previously shown to contain a J-domain; however, this the first known example of the acquisition of a complete J-like protein by a virus and suggests that HSV has taken advantage of the adaptable nature of J-proteins to evolve a multi-functional co-chaperone that functions with Hsc70 to promote lytic infection.IMPORTANCEViruses have evolved a variety of strategies to succeed in a hostile environment. The HSV immediate early protein ICP22 plays several roles in the virus life cycle including down-regulation of cellular gene expression, up-regulation of late viral gene expression, inhibition of apoptosis, prevention of aggregation of non-native proteins and the recruitment of a cellular heat shock protein, Hsc70, to nuclear domains. We present evidence that ICP22 resembles a cellular J-protein/HSP40 family co-chaperone, interacting specifically with Hsc70. This is the first known example of the acquisition of a complete J-like protein by a virus and suggests that HSV has evolved to manipulate the host proteostatic machinery during the establishment of lytic infection.
A new tool CovReport generates easy-to-understand sequencing coverage summary for diagnostic reports
Authors: Gorokhov Mark , Cerino Mathieu , Bartoli Marc , Krahn Martin , Gorokhova Svetlana 
Published: June 2019

AbstractIn order to properly interpret the results of a diagnostic gene panel sequencing test, gene coverage needs to be taken into consideration. If coverage is too low, an additional re-sequencing test is needed to make sure that a pathogenic variant is not missed. To facilitate the interpretation of coverage data, we designed CovReport, a novel easy-to-use visualization tool. CovReport generates a concise coverage summary that allows one-glance assessment of the sequencing test performance. Both gene-level and exon-level coverage can be immediately appreciated and taken into consideration for further medical decisions. CovReport does not require complex installation and can thus be easily implemented in any diagnostic laboratory setting. A user-friendly interface generates a graphic summary of coverage that can be directly included in the diagnostic report. In addition to a stand-alone version, we also provide a command line version of CovReport that can be integrated into any bioinformatics pipeline. This flexible tool is now part of routine sequencing analysis at the Department of Medical Genetics at La Timone Hospital (Marseille, France).Availability and implementationCovReport is available at http://jdotsoft.com/CovReport.php. It is implemented in Java and supported on Windows, Mac OS X and Linux.Abstract Figure
Systematic evaluation of the helicopter rotor blades: design variables and interactions
Authors: Shahmiri Farid , Sargolzehi Maryam , Shahi Ashtiani Mohammad Ali 
Published: June 2019

Purpose
The effects of rotor blade design variables and their mutual interactions on aerodynamic efficiency of helicopters are investigated. The aerodynamic efficiency is defined based on figure of merit (FM) and lift-to-drag responses developed for hover and forward flight, respectively.

Design/methodology/approach
The approach is to couple a general flight dynamic simulation code, previously validated in the time domain, with design of experiment (DOE) required for the response surface development. DOE includes I-optimality criteria to preselect the data and improve data acquisition process. Desirability approach is also implemented for a better understanding of the optimum rotor blade planform in both hover and forward flight.

Findings
The resulting system provides a systematic manner to examine the rotor blade design variables and their interactions, thus reducing the time and cost of designing rotor blades. The obtained results show that the blade taper ratio of 0.3, the point of taper initiation of about 0.64 R within a SC1095R8 airfoil satisfy the maximum FM of 0.73 and the maximum lift-to-drag ratio of about 5.5 in hover and forward flight.

Practical implications
The work shows the practical possibility to implement the proposed optimization process that can be used for the advanced rotor blade design.

Originality/value
The work presents the rapid and reliable optimization process efficiently used for designing advanced rotor blades in hover and forward flight.
Miniature as a way of representation in design studio: a case study
Authors: Zeybekoglu Senem , Sadri Hossein 
Published: June 2019

Purpose
Learning from traditional miniature painting and from recent studies on their modern and creative applications, the purpose of this paper is to identify the key qualifications of miniature and possible ways for using miniature in urban design studios. Following discussions on the pedagogical and professional effects of using miniature in a design studio, the paper introduces De-Urban Design Studio’s philosophy and its experience in employing miniature as a way of representation as the case study.

Design/methodology/approach
Different from the urban design’s professional role which materialized in conventional architectural presentation, miniature appears as a representation way in the search for the appropriate media for the de-urban design’s activist model.

Findings
Expressing the philosophy of transition design and de-urbanization, and studying some of the miniatures produced in the De-Urban Design studio, this paper sheds light on the possibilities created by the usage of miniature in urban design studio as a communication medium in making the processes of design more inclusiveness, participatory and democratic.

Originality/value
The term miniatecture is used for the first time as a representation technique developed in the De-Urban Design Studio co-instructed by the authors of this paper.
An improved immune clonal selection algorithm for bi-objective robotic assemble line balancing problems considering time and space constraints
Authors: Zhou Binghai , Wu Qiong 
Published: June 2019

Purpose
The extensive applications of the industrial robots have made the optimization of assembly lines more complicated. The purpose of this paper is to develop a balancing method of both workstation time and station area to improve the efficiency and productivity of the robotic assembly lines. A tradeoff was made between two conflicting objective functions, minimizing the number of workstations and minimizing the area of each workstation.

Design/methodology/approach
This research proposes an optimal method for balancing robotic assembly lines with space consideration and reducing robot changeover and area for tools and fixtures to further minimize assembly line area and cycle time. Due to the NP-hard nature of the considered problem, an improved multi-objective immune clonal selection algorithm is proposed to solve this constrained multi-objective optimization problem, and a special coding scheme is designed for the problem. To enhance the performance of the algorithm, several strategies including elite strategy and global search are introduced.

Findings
A set of instances of different problem scales are optimized and the results are compared with two other high-performing multi-objective algorithms to evaluate the efficiency and superiority of the proposed algorithm. It is found that the proposed method can efficiently solve the real-world size case of time and space robotic assembly line balancing problems.

Originality/value
For the first time in the robotic assembly line balancing problems, an assignment-based tool area and a sequence-based changeover time are took into consideration. Furthermore, a mathematical model with bi-objective functions of minimizing the number of workstations and area of each station was developed. To solve the proposed problem, an improved multi-objective immune clonal selection algorithm was proposed and a special coding scheme is designed.
Pedagogical strategies for developing interpretive language about images
Authors: Ravelli Louise 
Published: June 2019

Purpose
The purpose of this paper is to reflect on pedagogical strategies which support the teaching of critical analysis of visual and multimodal texts in a tertiary-level course for Arts students.

Design/methodology/approach
The paper describes strategies which focus on developing students’ abilities to express interpretive critique, as opposed to mere description. These strategies give students strong scaffolding towards success in their interpretive writing. The course in question is a tertiary-level Arts course which teaches Kress and van Leeuwen’s (2006) approach to “reading images” in relation to contemporary media texts. The basic structure of the course is described, along with the macro steps which underpin the pedagogy. Examples of highly successful and less successful student writing are compared to reveal the key components of effective interpretive answers.

Findings
In addition to the normal expectations regarding essay structure and style, and in addition to mastery of the technicality of the course, successful and less successful student writing depends on their mastery of a specific set of moves within the essay. These moves integrate textual observations with clear explanations and a strong relation to interpretation.

Practical implications
While the course and strategies discussed are for tertiary-level students, the strategies described are adaptable to primary and secondary levels also. Multimodal texts are an integral part of the English curriculum, and all teachers need to explore strategies for enabling their students’ critical engagement with such texts.

Originality/value
Visual and multimodal texts are an exciting and also challenging part of English curricula, and new analytical frameworks and pedagogical strategies are needed to tackle these texts. In particular, the gap between simply describing visual resources (applying the tools) and critical analysis (using the tools) is vast, and specific pedagogical strategies are needed to help students develop the necessary interpretive language.
Consumer behaviour towards pharmaceutical products: a model development
Authors: Ting Chuo Yew , Ismail Mazlan Bin , Ting Hiram , Bahri Salmah Binti , Sidek Affarizan Bin , Idris Siti Fatimah Bt , Tan Robin Tiow Heng , Abu Seman Sareh Safwan Bin , Sethiaram Mogan Ram A_L , Md Ghazali Mohd Hazwan Bin , Lim Qin Hui , Mohd Zaki Mohamad Soliheen Bin , Sohot Mohammad Shamil Bin 
Published: June 2019

Purpose
Despite the extant literature on purchasing behaviour, little is known about why and how consumers purchase and use pharmaceutical products in Malaysia. This paper aims to develop a holistic model that articulates the factors underlying pharmaceutical product purchase and use and their relationships.

Design/methodology/approach
Drawing upon the grounded theory approach, in-depth interviews and analysis on the basis of theoretical saturation were conducted. Enumerators, trained to perform interviews, the transcription and content analysis, sampled 120 Malaysian consumers in the first phase and 40 in the second. ATLAS.ti was used to assist the coding and analytical process.

Findings
The findings largely support extant literature on purchasing decisions. Particularly, the evaluation of product attributes was found to be an immediate determinant of purchase and use. The effect, in turn, was moderated by personal factors and facilitating conditions. The need for healthcare products and the knowledge about them were constructed as antecedents in the model. The study also highlights that consumers’ purchase and use of pharmaceutical products could be better understood and managed with a holistic view of the decision-making process.

Originality/value
This study proposes the conbe-hepro model to explicate the antecedents and determinants of consumers’ purchase and use of pharmaceutical products in the Malaysian context. It provides a theoretical grounding that enriches our knowledge of the changing behaviour of consumers in healthcare literature. It also yields practical insights to the government bodies and the healthcare providers in Malaysia and other developing countries.
Non-clinical rounds in hospital settings: a scoping review
Authors: Angelopoulou Paraskevi , Panagopoulou Efharis 
Published: June 2019

PurposeThe purpose of this paper is to systematically describe the types of non-clinical rounds implemented in hospital settings.Design/methodology/approachThis scoping review was conducted and reported in accordance with the PRISMA. The review followed the four stages of conducting scoping review as defined by Arskey and O’Malley (2005).FindingsInitially, 978 articles were identified through database search from which only 24 studies were considered relevant and included in the final review. Overall, eight types of non-clinical rounds were identified (death rounds, grand rounds, morbidity and mortality conferences, multidisciplinary rounds, patient safety rounds, patient safety huddles, walkarounds and Schwartz rounds) that independently of their format, goal, participants and type of outcomes aimed to enhance patient safety and improve quality of healthcare delivery in hospital settings, either by focusing on physician, patient or organizational system.Originality/valueTo the authors’ knowledge this is the first review that aims to provide a comprehensive summary to the types of non-clinical rounds that has been applied in clinical settings.
Competencies for effective public middle managers
Authors: Sudirman Iman , Siswanto Joko , Monang Joe , Aisha Atya Nur 
Published: June 2019

Purpose
The purpose of this paper is to investigate a set of competencies that characterizes effective public middle managers.

Design/methodology/approach
A total of 20 middle managers from several public agencies were interviewed in person using the behavioral event interview technique. In all, 80 stories were deductively coded based on the existing National Civil Service Agency’s managerial competency dictionary and inductively examined through a thematic analysis to discover new themes.

Findings
This study’s findings suggest that communication, organizing, information seeking, analytical thinking and planning competencies are common competencies, but essential for effective public middle managers. Conversely, achievement orientation, leadership, directiveness, persuasiveness and innovation are competencies that characterize effective public middle managers and distinguish them from average performers. In addition, some other new competencies inductively obtained using a thematic analysis are also important for effective public managers: adherence to laws and regulations, multi-stakeholder collaboration, and technical competencies (technology management, human resource management and financial management).

Research limitations/implications
The research was undertaken using 20 samples divided into superior and average performers; thus, it is limited to developing competency levels to new competencies.

Originality/value
This study identifies the competencies necessary for effective middle managers within the public sector context. Conducting behavioral event interviews with two distinct groups provides empirically unique behavioral evidence of competencies that characterize effective public middle managers and enables to discover new competencies.