The interplay of customer experience and commitment

Purpose This research aims to better understand customer experience, as it relates to customer commitment and provides a framework for future research into the intersection of these emerging streams of research. Design/methodology/approach This research contributes to theoretical and practical perspectives on customer experience and its measurement by integrating extant literature with customer commitment and customer satisfaction literature. Findings The breadth of the domains that encompass customer experience – cognitive, emotional, physical, sensorial and social – makes simplistic metrics impossible for gauging the entirety of customers’ experiences. These findings provide strong support of the need for new research into customer experience and customer commitment. Practical implications Given the complexity of customer experience, managers are unlikely to track and manage all relevant elements of the concept. This research provides a framework identifying empirically the most salient attributes of customer experience with particular emphasis on those elements that enhance commitment. This offers insight into service design to correspond with specific commitment and experience dimensions. Originality/value This research is the first to examine the customer experience as it relates to customer commitment – a key factor in customer loyalty, positive word of mouth and other desired outcomes for managers and marketers. This paper provides a framework for future research into these emerging topics. </jats:sec

Mesoscale modeling and simulation of microstructure evolution during dynamic recrystallization of a Ni-based superalloy

Microstructural evolution and plastic flow characteristics of a Ni-based superalloy were investigated using a simulative model that couples the basic metallurgical principle of dynamic recrystallization (DRX) with the twodimensional (2D) cellular automaton (CA). Variation of dislocation density with local strain of deformation is considered for accurate determination of the microstructural evolution during DRX. The grain topography, the grain size and the recrystallized fraction can be well predicted by using the developed CA model, which enables to the establishment of the relationship between the flow stress, dislocation density, recrystallized fraction volume, recrystallized grain size and the thermomechanical parameters

CSN-mediated deneddylation differentially modulates Ci155 proteolysis to promote Hedgehog signalling responses

The Hedgehog (Hh) morphogen directs distinct cell responses according to its distinct signalling levels. Hh signalling stabilizes transcription factor cubitus interruptus (Ci) by prohibiting SCFSlimb-dependent ubiquitylation and proteolysis of Ci. How graded Hh signalling confers differential SCFSlimb-mediated Ci proteolysis in responding cells remains unclear. Here, we show that in COP9 signalosome (CSN) mutants, in which deneddylation of SCFSlimb is inactivated, Ci is destabilized in low-to-intermediate Hh signalling cells. As a consequence, expression of the low-threshold Hh target gene dpp is disrupted, highlighting the critical role of CSN deneddylation on low-to-intermediate Hh signalling response. The status of Ci phosphorylation and the level of E1 ubiquitin-activating enzyme are tightly coupled to this CSN regulation. We propose that the affinity of substrate–E3 interaction, ligase activity and E1 activity are three major determinants for substrate ubiquitylation and thereby substrate degradation in vivo

Citalopram reduces aggregation of ATXN3 in a YAC transgenic mouse model of Machado-Joseph disease

Machado-Joseph disease, also known as spinocerebellar ataxia type 3, is a fatal polyglutamine disease with no disease-modifying treatment. The selective serotonin reuptake inhibitor citalopram was shown in nematode and mouse models to be a compelling repurposing candidate for Machado-Joseph disease therapeutics. We sought to confirm the efficacy of citalopram to decrease ATXN3 aggregation in an unrelated mouse model of Machado-Joseph disease. Four-week-old YACMJD84.2 mice and non-transgenic littermates were given citalopram 8 mg/kg in drinking water or water for 10 weeks. At the end of treatment, brains were collected for biochemical and pathological analyses. Brains of citalopram-treated YACMJD84.2 mice showed an approximate 50% decrease in the percentage of cells containing ATXN3-positive inclusions in the substantia nigra and three examined brainstem nuclei compared to controls. No differences in ATXN3 inclusion load were observed in deep cerebellar nuclei of mice. Citalopram effect on ATXN3 aggregate burden was corroborated by immunoblotting analysis. While lysates from the brainstem and cervical spinal cord of citalopram-treated mice showed a decrease in all soluble forms of ATXN3 and a trend toward reduction of insoluble ATXN3, no differences in ATXN3 levels were found between cerebella of citalopram-treated and vehicle-treated mice. Citalopram treatment altered levels of select components of the cellular protein homeostatic machinery that may be expected to enhance the capacity to refold and/or degrade mutant ATXN3. The results here obtained in a second independent mouse model of Machado-Joseph disease further support citalopram as a potential drug to be repurposed for this fatal disorder.This work was funded by Becky Babcox Research Fund/pilot research award G015617, University of Michigan to M.C.C. and NINDS/NIH R01NS038712 to H.L.P. The work performed at the University of Minho was funded by the European Regional Development Funds (FEDER), through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038. This article was developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Program (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the FEDER. This work was also supported by FCT and COMPETE through the projects [PTDC/SAU-GMG/112617/2009] (to P.M.) and [EXPL/BIM-MEC/ 0239/2012] (to A.T.C.); by FCT through the project [POCI-01-0145- FEDER-016818 (PTDC/NEU-NMC/3648/2014)] (to P.M.); by National Ataxia Foundation (to P.M. and to A.T.C.); and by Ataxia UK (to P.M.). S.D.S. and A.T.C. were supported by fellowships from FCT, SFRH/BD/ 78388/2011 and SFRH/BPD/102317/2014, respectively. FCT fellowships are co-financed by POPH, QREN, Governo da República Portuguesa and EU/FSE

Coping Mediates the Association Between Type D Personality and Perceived Health in Chinese Patients with Coronary Heart Disease

Background: Increasing evidence show that Type D personality is a risk factor for morbidity, mortality, and quality of life of patients with coronary vascular disease. Few studies examined coping as a potential behavioral mechanism to explain the harmful effect of Type D personality. Purpose: This study examined the association between Type D personality, coping, and perceived health among Chinese patients with coronary heart disease (CHD). Methods: One hundred seventeen CHD patients completed the assessments on Type D personality, coping, perceived severity of CHD, and morale. Results: There was no difference on severity of coronary artery stenosis between Type D and non-Type D patients. Compared to the non-Type D patients, the Type D patients perceived higher severity of CHD (5.31±2.41 versus 4.45±2.17, p<0.05) and lower morale (12.67±4.71 versus 15.00±4.43, p<0.05), and used less confrontation (16.90±5.39 versus 20.88±4.95, p<0.001) and more acceptance-resignation coping (10.16±3.50 versus 8.35±3.48, p<0.05). Mediation analyses showed that confrontation coping mediated the association between Type D personality and perceived severity of disease, and acceptance-resignation coping mediated the association between Type D personality and morale after controlling for age, gender, and clinical variables. Conclusion: The Type D patients used maladaptive coping in response to disease. These coping strategies fully mediated the association between Type D personality and perceived health. Implications for integrating coping training into the intervention for patients with a Type D personality are discussed. © 2010 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201

Impact of vitamin D metabolism on clinical epigenetics

The bioactive vitamin D (VD) metabolite, 1,25-dihydroxyvitamin D3 regulates essential pathways of cellular metabolism and differentiation via its nuclear receptor (VDR). Molecular mechanisms which are known to play key roles in aging and cancer are mediated by complex processes involving epigenetic mechanisms contributing to efficiency of VD-activating CYP27A1 and CYP27B1 or inactivating CYP24 enzymes as well as VDR which binds to specific genomic sequences (VD response elements or VDREs). Activity of VDR can be modulated epigenetically by histone acetylation. It co-operates with other nuclear receptors which are influenced by histone acetyl transferases (HATs) as well as several types of histone deacetylases (HDACs). HDAC inhibitors (HDACi) and/or demethylating drugs may contribute to normalization of VD metabolism. Studies link VD signaling through the VDR directly to distinct molecular mechanisms of both HAT activity and the sirtuin class of HDACs (SIRT1) as well as the forkhead transcription factors thus contributing to elucidate complex epigenetic mechanisms for cancer preventive actions of VD