bluuebunny/crossref_metadata_2025_split huggingface dataset:
Duo-activation of PKA and PKG by PDE1 inhibition facilitates proteasomal degradation of misfolded proteins and protects against proteinopathy
Authors: Zhang Hanming , Pan Bo , Rekhter Mark D. , Goldberg Alfred L. , Wang Xuejun 
Published: February 2019

AbstractNo current treatment is intended to target cardiac proteotoxicity or can reduce mortality of heart failure with preserved ejection fraction (HFpEF), a prevalent form of heart failure (HF). Selective degradation of misfolded proteins by the ubiquitin-proteasome system (UPS) is vital to the cell. Proteasome impairment is recently implicated in HF genesis. Activation of the cGMP-protein kinase G (PKG) or the cAMP-protein kinase A (PKA) pathways facilitates proteasome functioning. Phosphodiesterase 1 (PDE1) hydrolyzes both cyclic nucleotides and accounts for the majority of PDE activities in human myocardium. Here we report the preclinical therapeutic efficacy and a new mechanism of action of PDE1 inhibition (IC86430) for cardiac proteinopathy caused by Arg120Gly missense mutant αB-crystallin (CryABR120G). In mice expressing GFPdgn, an inverse reporter of UPS proteolytic activity, IC86430 treatment increased myocardial 26S proteasome activities and substantially decreased GFPdgn protein levels. Myocardial PDE1A expression was highly upregulated in CryABR120Gmice. HFpEF was detected in CryABR120Gmice at 4 months; IC86430 treatment initiated at this stage markedly attenuated HFpEF, substantially delayed mouse premature death, increased myocardial levels of Ser14-phosphorylated Rpn6, and reduced the steady state level of the misfolded CryAB species in these mice. In cultured cardiomyocytes, IC86430 treatment increased proteasome activities and accelerated proteasomal degradation of GFPu and CryABR120Gin a PKA- and PKG- dependent manner. We conclude that PDE1 inhibition induces PKA- and PKG-mediated promotion of proteasomal degradation of misfolded proteins in cardiomyocytes and effectively treats HFpEF caused by CryABR120G; hence, PDE1 inhibition represents a potentially new therapeutic strategy for HFpEF and heart disease with increased proteotoxic stress.One Sentence SummaryPDE1 inhibition enhances proteasomal degradation of misfolded proteins in a PKA and PKG dependent manner and protects against cardiac proteinopathy and heart failure with preserved ejection fraction.
Integrative analysis of Hydra head regeneration reveals activation of distal enhancer-like elements
Authors: Murad Rabi , Macias-Muñoz Aide , Wong Ashley , Ma Xinyi , Mortazavi Ali 
Published: February 2019

AbstractThe cnidarian model organism Hydra has long been studied for its remarkable ability to regenerate its head, which is controlled by a head organizer located near the hypostome. Cnidarians and bilaterians diverged about 600 millions years ago but the gene contents of species of both phyla are surprisingly similar despite divergent morphologies and functions. While little is known about the role ofcis-regulatory elements in cnidarians, understanding gene regulatory mechanisms in cnidarians can potentially shed light on metazoan evolution. The canonical Wnt pathway plays a central role in head organizer function during regeneration and during bud formation, which is the asexual mode of reproduction in Hydra. However, it is unclear how shared the developmental programs of head organizer genesis are in budding and regeneration. Time-series analysis of gene expression changes during head regeneration and budding revealed a set of 298 differentially expressed genes during the 48-hour head regeneration and 72-hour budding time-courses. In order to understand the regulatory elements controlling hydra head regeneration, we first identified 27,137 open-chromatin elements that are open in one or more sections of organism. We used histone modification ChIP-seq to identify 9998 candidate proximal promoter and 3018 candidate enhancer-like regions respectively. We show that a subset of these regulatory elements is dynamically remodeled during head regeneration and identify a set of transcription factor motifs that are enriched in the enhancer regions activated during head regeneration. Our results show that Hydra displays complex gene regulatory structures of developmentally dynamic enhancers, which suggests that the evolution of complex developmental enhancers predates the split of cnidarians and bilaterians.
Pathogenic potential of Hic1 expressing cardiac stromal progenitors
Authors: Soliman H , Paylor B , Scott W , Lemos DR , Chang CK , Arostegui M , Low M , Lee C , Fiore D , Braghetta P , Pospichalova V , Barkauskas CE , Korinek V , Rampazzo A , MacLeod K , Underhill TM , Rossi FM 
Published: February 2019

AbstractThe cardiac stroma contains multipotent mesenchymal progenitors. However, lineage relationships within cardiac stromal cells are still poorly understood. Here, we identify heart-resident PDGFRa+Sca-1+cells as cardiac Fibro/Adipogenic Progenitors (cFAPs) and show that they respond to ischemic damage by generating fibrogenic cells. Pharmacological blockade of this differentiation step with an anti-fibrotic tyrosine kinase inhibitor decreases post-myocardial infarction (MI) remodeling and leads to improvements in heart function. In the undamaged heart, activation of cFAPs through lineage-specific deletion of the quiescence factor Hic1 reveals additional pathogenic potential, causing fibro-fatty infiltration of the myocardium and driving major pathological features of Arrhythmogenic Cardiomyopathy (AC).HighlightsA subpopulation of PDGFRa+, Sca-1+cells, previously considered to be a sub-type of cardiac fibroblasts, are multipotent mesenchymal progenitors,Cardiac damage triggers the differentiation of PDGFRa+Sca-1+cells into Sca-1-cells expressing a fibrogenic transcriptional programme,Blockade of the cFAP-to-fibroblast transition by Nilotinib ameliorated cardiac dysfunction post-MI and modulated cardiac remodelling.Studies performed on a model of experimentally-induced AC confirmed that cFAPs are a source of both cardiac fibroblasts and adipocytesin vivo.Conversely, in the undamaged heart, activation of cFAPs by means of lineage-specific deletion of transcription factor Hic1, resulted in fibro/fatty cardiac degeneration and pathological alterations reminiscent of AC. Collectively, our findings show that a proportion of what are commonly termed “fibroblasts” are actually multipotent mesenchymal progenitors that contribute to different forms of cardiac degeneration depending on the damage setting.
A critical appraisal of the international factors in “One Country, Two Systems” and democratization in Hong Kong
Authors: Chan Kenneth Ka Lok , Chong King Man Eric 
Published: February 2019

Purpose
The purpose of this paper is to present an analytical framework to examine the impact of international factors on “One Country, Two Systems” in general and Hong Kong’s democratization in particular.

Design/methodology/approach
The paper has adopted a behavioral approach to identify the agents, mechanisms and observable facets of external–internal interactions.

Findings
The need for international recognition on the performance of the Hong Kong Special Administrative Region (HKSAR) under Chinese sovereignty has provided external actors with the necessary leverage. Though the impact of the international community has been indirect and limited, the authors have identified two mechanisms – lesson drawing and socialization – whereby the impact of international actors and their actions towards Hong Kong may be subtly felt. Moreover, there are at least three observable facets of external actions which are pertinent to the democracy issue. At the end of day, the external impacts will be determined not by the international actors per se but the balance of power between the domestic actors in Hong Kong.

Originality/value
There is a scholarly consensus that international factors matter to Hong Kong. But there has been a lack of serious investigation as to why and how they matter. The observable facets of external–internal interactions and the mechanisms identified in this work have not only enriched our understanding of the relevance of external factors in Hong Kong affairs, but also provided a sound foundation for future research.
The ties that bind: mutuality of political destiny between Hong Kong and Taiwan
Authors: Wong Wai Kwok Benson 
Published: February 2019

Purpose
The purpose of this paper is to explain how post-1997 Hong Kong has been perceived in Taiwan and to critically evaluate the demonstration effects of Hong Kong under the “One Country, Two Systems” policy on cross-strait relations.

Design/methodology/approach
“Today’s Hong Kong, Tomorrow’s Taiwan” has become a dominant discourse in cross-strait relations in recent years. The paper has adopted discourse analysis of selected texts during and after the 2014 Sunflower Movement to elucidate the disapproval of the developments of post-handover Hong Kong and the construction of the Movement’s self-identity.

Findings
It has observed the following arguments which shaped the prevailing perceptions among critics of the “One Country, Two Systems” policy: political infiltration of China in Hong Kong could be extended to Taiwan in the sense that the Beijing authorities would adopt the identical approach to manipulate Taiwan through the cross-strait trading agreements; negative perceptions and images of China and Chinese capitals as a collective aggressor and a threat, raising fear and worries in both Hong Kong and Taiwan; and Kuomintang, as a ruling party at that time under the leadership of President Ma Ying-jeoh, was dismissed by protesters as an incompetent gatekeeper and defender of Taiwan’s interests.

Originality/value
The pervasive sentiments and perceptions about post-1997 Hong Kong has been articulated discursively by the young activists in Taiwan and Hong Kong into a statement – “Today’s Hong Kong, Tomorrow’s Taiwan” – which has brought about a somewhat unexpected bonding effect between Hong Kong and Taiwan through a strong disapproval of “One Country, Two Systems” and the China factor, which has be reproduced, delivered and circulated in both societies since 2014.
Collaboration quality assessment for sustainable supply chains: benchmarking
Authors: Dania Wike Agustin Prima , Xing Ke , Amer Yousef 
Published: February 2019

PurposeThe purpose of this paper is to propose an instrument to evaluate the collaboration quality of sustainable supply chains by considering collaboration behaviour and sustainability factors.Design/methodology/approachThe proposed model integrates Quality Function Deployment (QFD), Fuzzy Analytical Network Process (FANP) and Data Envelopment Analysis (DEA) to assess the efficiency score of each stakeholder involved. A case of a sugar company in Indonesia was analysed as the illustration of the application of the model.FindingsThe integrated QFD-FANP-DEA method enables to incorporate collaboration behaviour and sustainability factors in a single assessment model. The results of the case study showed the benchmarking results associated with the performance variance of stakeholders and the number of samples.Research limitations/implicationsFuture research could consider other DEA approaches, extend the research by simulating a different number of scenarios and evaluating the improvement/deterioration, and expand the scope of collaboration.Practical implicationsEach stakeholder will be able to obtain the collaboration assessment results, and the improvements suggested by the model.Social implicationsSmallholders and farmers will be able to increase their benefits by using the existing resources.Originality/valueThis paper provides a methodological contribution by introducing new collaboration quality assessment methods that can accommodate any variance in multi-stakeholders, involve qualitative and quantitative measurements, and benefit all stakeholders.
Green Agrevolution Pvt Ltd: delivering 360° “seed-to-market” solution
Authors: Sinha Aditya , Jha Suresh , Amritesh Amritesh 
Published: February 2019

Learning outcomes
The purpose of this paper is to introduce learners to a successful Agri-start-up where they can explore the existing challenges and critical strategic decisions for the firm’s growth.

Case overview/synopsis
Shashank, the CEO and co-founder of an agriculture-based Indian start-up Green Agrevolution Pvt Ltd (GAPL), is planning to reach out to more than one million farmers by 2021-2022, which is more than 20 times of the present volume. His team is presently serving around 42,000 farmers with a home-grown technological platform DeHaat which provides end–to-end services right from seed to the market. Micro-entrepreneurs are selected and groomed to act as local touchpoints for farmers in the respective catchment areas ranging from 3 to 5 km. Shashank has been a recipient of multiple accolades and recognition and is now firmly seated to drive his start-up to the next level of growth and pan-India market penetration. The venture also requires an understanding of segment-specific needs, cropping pattern, using local resources and channelizing the advisory services to occupy a central role in the value chain. There are other impending issues such as low smartphone adoption, low internet access and lack of entrepreneurial mindset among the rural youth. Similar issues were relatively backward states of India with little or no provision of app-based services. Will he be successful to expand on such a high pace in other States with the existing resources and capabilities?

Complexity academic level
Senior undergraduate and Master's level business students

Supplementary materials
Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code
CSS 11: Strategy
Corporate social responsibility in tourism as a tool for sustainable development
Authors: Hatipoglu Burcin , Ertuna Bengi , Salman Duygu 
Published: February 2019

PurposeThis study aims to analyze corporate social responsibility (CSR) programs in tourism as a tool for sustainable development in the CSR program of a multinational enterprise in Turkey.Design/methodology/approachThis study includes qualitative research on a single company, content analysis of company-originated documents, participant observations, questionnaires for tourism project coordinators and follow-up interviews with company directors and project managers.FindingsThe paper identifies immediate context variables, program management, the complementary nature of interests and the diverse capabilities of the partners and an ongoing evaluation process as the determining factors for creating shared value for CSR programs in tourism.Research limitations/implicationsDespite the challenges of impact assessment and measurement of long-term effects, the study proposes a systematic framework for evaluating shared value creation generated by CSR activity.Practical implicationsThe evaluation methodology introduced in this research will be of use to CSR program developers in interpreting and reporting on the anticipated outcomes and impacts of their interventions in sustainable tourism development.Social implicationsA lack of outcome evaluation and impact assessment may affect accountability and, hence, the legitimacy of CSR programs. This study attempts to mitigate that limitation by introducing a novel methodology.Originality/valueThe value of CSR in tourism is a highly contested issue, despite its high potential for contributing to sustainable development. This longitudinal research goes beyond presenting immediate outputs of a CSR program in sustainable tourism; it discusses intermediate outcomes in the form of capitals, community well-being and shared value for society at large.
Investigating the influence of performance measurement on learning, entrepreneurial orientation and performance in turbulent markets
Authors: Taheri Babak , Bititci Umit , Gannon Martin Joseph , Cordina Renzo 
Published: February 2019

PurposeThis study aims to examine how comprehensive performance measurement systems (CPMS) influence entrepreneurial orientation, market-focussed learning (MFL) and employees’ perceptions of firm performance within a service-provision context. It also considers the moderating effect of low and high levels of perceived market-turbulence (low-turbulence environments [LMT] vs highly turbulent environments [HMT]) on the relationships between these concepts.Design/methodology/approachPLS-SEM was used to test the hypothesised relationships using survey responses from 198 employees of a leading multi-branch travel agency in Iran.FindingsThe findings demonstrate that CPMS positively influence MFL and, in doing so, have a positive effect on perceptions of firm performance. However, the findings also suggest that CPMS negatively influence entrepreneurial orientation, and therefore can also negatively influence perceptions of firm performance. Further, the relationships between CPMS, entrepreneurial orientation, MFL and firm performance are stronger for HMT when compared to LMT for all relationships.Practical implicationsIndustry managers should adapt their CPMS to include measures specific to intra-organisational entrepreneurship and innovation and should pursue greater understanding of changing customer preferences.Originality/valueThis study highlights the importance of MFL as a means of avoiding the negative impact of underdeveloped market research on performance in the turbulent Iranian context. Contrary to previous literature, it provides an example of how CPMS can negatively influence entrepreneurial orientation in such environments.
Unethical consumer behavior: the role of institutional and socio-cultural factors
Authors: Agnihotri Arpita , Bhattacharya Saurabh 
Published: February 2019

PurposeThe purpose of this study is to explore how institutional trust, frugality and materialism motivate consumers’ unethical behavior.Design/methodology/approachThe authors conducted the study in two phases – qualitative and quantitative. In the qualitative phase through a content analysis of semi-structured interviews, a list of unethical activities was obtained. In the quantitative phase, a questionnaire was developed, which had questions related to the unethical activities. Data collection for the quantitative phase was achieved through mall intercept surveys. The collected data were subjected to exploratory factor analysis, confirmatory factor analysis and multivariate regression analysis.FindingsPoor institutional environment, frugal attitude and materialistic values motivate consumers from an emerging economy to indulge in unethical acts some of which were not explored before such as booking a cab but not boarding or stealing electricity.Originality/valueResearch evidence on unethical consumer behavior is lacking from emerging markets. Furthermore, extant studies have used mainly national culture models to explore unethical behavior, and finally, the role of institutional trust and frugality has not been explored in previous studies. The present study tries to fill these gaps by considering these elements as the cornerstone of this study.
A study on behaviour of bullwhip effect in (R, S) inventory control system considering DWT-MGGP demand forecasting model
Authors: Jaipuria Sanjita , Mahapatra Siba Sankar 
Published: February 2019

Purpose
The purpose of this paper is to propose a forecasting model to predict the demand under uncertain environment to control the bullwhip effect (BWE) considering review-period order-up-to level ((R, S)) inventory control policy and its different variants such as (R, βS) (R, γO) and (R, γO, βS) proposed by Jakšič and Rusjan, (2008) and Bandyopadhyay and Bhattacharya (2013).

Design/methodology/approach
A hybrid forecasting model has been developed by combining the feature of discrete wavelet transformation (DWT) and an intelligence technique, multi-gene genetic programming (MGGP), denoted as DWT-MGGP. Performance of DWT-MGGP model has been verified under (R, S) inventory control policy considering demand from three different manufacturing companies.

Findings
A comparison between DWT-MGGP model and autoregressive integrated moving average forecasting model has been done by estimating forecast error and BWE. Further, this study has been extended with analysing the behaviour of BWE considering different variants of (R, S) policy such as (R,βS) (R, γO) and (R,γO,βS) and found that BWE can be moderated by controlling the inventory smoothing (β) and order smoothing parameters (γ).

Research limitations/implications
This study is limited to different variants of (R, S) inventory control policy. However, this study can be further extended to continuous review policy.

Practical implications
The proposed DWT-MGGP model can be used as a suitable demand forecasting model to control the BWE when (R, S), (R,βS) (R,γO) and (R,γO,βS)inventory control policies are followed for replenishment.

Originality/value
This study analyses the behavior of BWE through controlling the inventory smoothing (β) and order smoothing parameters (γ) when demand is predicted using DWT-MGGP forecasting model and order is estimated using (R, S), (R,βS) (R,γO) and (R,γO,βS) inventory control policies.
Design of a bi-manual haptic interface for skill acquisition in surface mount device soldering
Authors: James Jose , Rao R. Bhavani , Neamtu Gabriel 
Published: February 2019

Purpose
Offering unskilled people training in engineering and vocational skills helps to decrease unemployment rate. The purpose of this paper is to augment actual hands-on conventional vocational training methods with virtual haptic simulations as part of computer-based vocational education and training.

Design/methodology/approach
This paper discusses the design of a bi-manual virtual multi-modal training interface for learning basic skills in surface mount device hand soldering. This research aims to analyze human hand dexterity of novices and experts at micro level skill knowledge capture by simulating and tracking the users’ actions in the manual soldering process through a multi-modal user interface.

Findings
Haptic feedback can enhance the experience of a virtual training environment for the end user and can provide a supplementary modality for imparting tangible principles to increase effectiveness. This will improve the teaching and learning of engineering and vocational skills with touch-based haptics technology, targeted toward teachers and students of various disciplines in engineering. Compared with the traditional training methods for learning soldering skills, the proposed method shows more efficiency in faster skill acquisition and skill learning.

Originality/value
In this study, the authors proposed a novel bi-manual virtual training simulator model for teaching soldering skills for surface mount technology and inspection. This research aims to investigate the acquisition of soldering skills through virtual environment, with and without haptic feedback. This acts as a basic-level training simulator that provides introductory training in soldering skills and can help initially unskilled people find educational opportunities and job offers in the electronics industry.