Although performance pressure has desirable consequences, there is evidence that it can produce unintended outcomes as employees tend to engage in dysfunctional and unethical behaviors to meet performance goals. Thus, the process through which employees think and behave unethically under performance pressure deserves more research attention. This study goes beyond the stress-appraisal perspective and investigates whether and when performance pressure influences individual work mindsets and behaviors from a moral reasoning perspective. Specifically, we contend that performance pressure is related to employee (...) expediency through moral decoupling. We further hypothesize dialectical thinking and moral identity to be the boundary conditions of the proposed relationships. Analyses of data from a field study in three waves provide support for most of the hypotheses. In particular, we find that moral decoupling accounts for additional variance after we control for the stress-appraisal effect of performance pressure on employee expediency. The study offers several contributions to the literature on performance pressure and unethical behavior. (shrink)

Cyclin-dependent kinase 5 has been implicated in Alzheimer's disease pathogenesis. Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A p25/cdk5 responsive region containing multiple sites for signal transducer and activator of transcription was identified in the BACE1 promoter. STAT3 interacts with the BACE1 promoter, and p25-overexpressing mice had elevated levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels. Furthermore, mice with a (...) targeted mutation in the STAT3 cdk5 responsive site had lower levels of BACE1. Increased BACE levels in p25 overexpressing mice correlated with enhanced amyloidogenic processing that could be reversed by a cdk5 inhibitor. These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis. (shrink)

OBJECTIVE: To report and analyse the pattern of end-of-life decision making for terminal Chinese cancer patients. DESIGN: Retrospective descriptive study. SETTING: A cancer clinical trials unit in a large teaching hospital. PATIENTS: From April 1992 to August 1997, 177 consecutive deaths of cancer clinical trial patients were studied. MAIN MEASUREMENT: Basic demographic data, patient status at the time of signing a DNR consent, or at the moment of returning home to die are documented, and circumstances surrounding these events evaluated. RESULTS: (...) DNR orders were written for 64.4% of patients. Patients in pain (odds ratio 0.45, 95% CI 0.22-0.89), especially if requiring opioid analgesia (odds ratio 0.40, 95% CI 0.21-0.77), were factors associated with a higher probability of such an order. Thirty-five patients were taken home to die, a more likely occurrence if the patient was over 75 years (odds ratio 0.12, 95% CI 0.04-0.34), had children (odds ratio 0.14, 95% CI 0.02-0.79), had Taiwanese as a first language (odds ratio 6.74, 95% CI 3.04-14.93), or was unable to intake orally (odds ratio 2.73, 95% CI 1.26-5.92). CPR was performed in 30 patients, none survived to discharge. CONCLUSIONS: DNR orders are instituted in a large proportion of dying Chinese cancer patients in a cancer centre, however, the order is seldom signed by the patient personally. This study also illustrates that as many as 20% of dying patients are taken home to die, in accordance with local custom. (shrink)

In this study, we examine the association between the ownership structure of Chinese listed firms and their audit choices among the Big 4, Second-tier, and Other firms between 2007 and 2012. The market share of the Big 4 firms in China was relatively low, while that of the Second-tier firms increasing during the sample period. Although there is little evidence to indicate that the audit quality of the Second-tier firms is not comparable to that of the Big 4 firms in (...) China, we find that large shareholders and boards of directors do not perceive the financial reporting credibility associated with the Second-tier firms to be the same as that of the Big 4 firms. We further find that the largest shareholders of Chinese listed firms prefer low-quality auditors when they have a low level of ownership but prefer high-quality auditors when they have a high level of ownership. The empirical evidence presented in this study should be of interest to regulators and academics. (shrink)

Objectives: To study the attitudes of both medical and non-medical students towards the do-not-resuscitate decision in a university in Hong Kong, and the factors affecting their attitudes.Methods: A questionnaire-based survey conducted in the campus of a university in Hong Kong. Preferences and priorities of participants on cardiopulmonary resuscitation in various situations and case scenarios, experience of death and dying, prior knowledge of DNR and basic demographic data were evaluated.Results: A total of 766 students participated in the study. There were statistically (...) significant differences in their DNR decisions in various situations between medical and non-medical students, clinical and preclinical students, and between students who had previously experienced death and dying and those who had not. A prior knowledge of DNR significantly affected DNR decision, although 66.4% of non-medical students and 18.7% of medical students had never heard of DNR. 74% of participants from both medical and non-medical fields considered the patient’s own wish as the most important factor that the healthcare team should consider when making DNR decisions. Family wishes might not be decisive on the choice of DNR.Conclusions: Students in medical and non-medical fields held different views on DNR. A majority of participants considered the patient’s own wish as most important in DNR decisions. Family wishes were considered less important than the patient’s own wishes. (shrink)

Chemotherapy is an important therapeutic approach for cancer treatment. However, drug resistance is an obstacle that often impairs the successful use of chemotherapies. Therefore, overcoming drug resistance would lead to better therapeutic outcomes for cancer patients. Recently, studies by our own and other groups have demonstrated that there is an intimate correlation between the loss of the F‐box and WD repeat domain‐containing 7 (FBW7) tumor suppressor and the incurring drug resistance. While loss of FBW7 sensitizes cancer cells to certain drugs, (...) FBW7‐/‐ cells are more resistant to other types of chemotherapies. FBW7 exerts its tumor suppressor function by promoting the degradation of various oncoproteins that regulate many cellular processes, including cell cycle progression, cellular metabolism, differentiation, and apoptosis. Since loss of the FBW7 tumor suppressor is linked to drug resistance, FBW7 may represent a novel therapeutic target to increase drug sensitivity of cancer cells to conventional chemotherapeutics. This paper thus focuses on the new functional aspects of FBW7 in drug resistance. (shrink)

Variations in levels of apolipoprotein E have been tied to the risk and progression of Alzheimer's disease . Our group has previously compared and contrasted the promoters of the mouse and human ApoE gene promoter sequences and found notable similarities and significant differences that suggest the importance of the APOE promoter's role in the human disease. We examine here three specific single-nucleotide polymorphisms within the human APOE promoter region, specifically at -491 , -427 , and at -219 upstream from the (...) +1 transcription start site. The -219 and -491 polymorphic variations have significant association with instance of AD, and -491AA has significant risk even when stratified for the APOEepsilon4 allele. We also show significant effects on reporter gene expression in neuronal cell cultures, and, notably, these effects are modified by species origin of the cells. The -491 and -219 polymorphisms may have an interactive effect in addition to any independent activity. DNA-protein interactions differ between each polymorphic state. We propose SP1 and GATA as candidates for regulatory control of the -491 and -219 polymorphic sites. This work's significance lies in drawing connection among APOE promoter polymorphisms' associations with AD to functional promoter activity differences and specific changes in DNA-protein interactions in cell culture-based assays. Taken together, these results suggest that APOE expression levels are a risk factor for AD irrespective of APOEepsilon4 allele status. (shrink)

Major hallmarks of Alzheimer's disease include brain deposition of the amyloid-beta peptide , which is proteolytically cleaved from a large Abeta precursor protein by beta and gamma- secretases. A transmembrane aspartyl protease, beta-APP cleaving enzyme , has been recognized as the beta-secretase. We review the structure and function of the BACE1 protein, and of 4129 bp of the 5'-flanking region sequence of the BACE1 gene and its interaction with various transcription factors involved in cell signaling. The promoter region and 5'-untranslated (...) region contain multiple transcription factor binding sites, such as AP-1, CREB and MEF2. A 91 bp fragment is the shortest region with significant reporter gene activity and constitutes the minimal promoter element for BACE1. The BACE1 promoter contains six unique functional domains and three structural domains of increasing sequence complexity as the "ATG" start codon is approached. Notably, the BACE1 gene promoter contains basal regulatory elements, inducible features and sites for regulation by various important transcription factors. Herein, we also discuss and speculate how the interaction of these transcription factors with the BACE1 promoter can modulate synaptic plasticity, neuronal apoptosis and oxidative stress, which are pertinent to the pathogenesis and progression of AD. (shrink)

BACKGROUND: Alzheimer's disease is intimately tied to amyloid-beta peptide. Extraneuronal brain plaques consisting primarily of Abeta aggregates are a hallmark of AD. Intraneuronal Abeta subunits are strongly implicated in disease progression. Protein sequence mutations of the Abeta precursor protein account for a small proportion of AD cases, suggesting that regulation of the associated gene may play a more important role in AD etiology. The APP promoter possesses a novel 30 nucleotide sequence, or "proximal regulatory element" , at -76/-47, from the (...) +1 transcription start site that confers cell type specificity. This PRE contains sequences that make it vulnerable to epigenetic modification and may present a viable target for drug studies. We examined PRE-nuclear protein interaction by gel electrophoretic mobility shift assay and PRE mutant EMSA. This was followed by functional studies of PRE mutant/reporter gene fusion clones. RESULTS: EMSA probed with the PRE showed DNA-protein interaction in multiple nuclear extracts and in human brain tissue nuclear extract in a tissue-type specific manner. We identified transcription factors that are likely to bind the PRE, using competition gel shift and gel supershift: Activator protein 2 , nm23 nucleoside diphosphate kinase/metastatic inhibitory protein , and specificity protein 1 . These sites crossed a known single nucleotide polymorphism . EMSA with PRE mutants and promoter/reporter clone transfection analysis further implicated PuF in cells and extracts. Functional assays of mutant/reporter clone transfections were evaluated by ELISA of reporter protein levels. EMSA and ELISA results correlated by meta-analysis. CONCLUSIONS: We propose that PuF may regulate the APP gene promoter and that AD risk may be increased by interference with PuF regulation at the PRE. PuF is targeted by calcium/calmodulin-dependent protein kinase II inhibitor 1, which also interacts with the integrins. These proteins are connected to vital cellular and neurological functions. In addition, the transcription factor PuF is a known inhibitor of metastasis and regulates cell growth during development. Given that APP is a known cell adhesion protein and ferroxidase, this suggests biochemical links among cell signaling, the cell cycle, iron metabolism in cancer, and AD in the context of overall aging. (shrink)

The apolipoprotein E gene plays an important role in the pathogenesis of Alzheimer's disease , and amyloid plaque comprised mostly of the amyloid-beta peptide ) is one of the major hallmarks of AD. However, the relationship between these two important molecules is poorly understood. We examined how A treatment affects APOE expression in cultured cells and tested the role of the transcription factor NF-B in APOE gene regulation. To delineate NF-B's role, we have characterized a 1098 nucleotide segment containing the (...) 5'-flanking region of the human APOE gene . Sequence analysis of this region suggests the presence of two potential NF-B elements. To demonstrate promoter activity, the region was cloned upstream of a promoterless luciferase gene. This segment was able to drive expression of luciferase in transient transfections of human fetal glial cells. Promoter activity was stimulated twofold by A treatment. Pretreatment with double-stranded DNA decoy oligonucleotides against NF-B reduced A stimulation. Deletion and mutagenetic analyses demonstrated that the distal NF-B element was functional and showed a strong DNA-protein complex band in gel shift analysis, similar to that from control NF-B consensus element. An anti-inflammatory and anti-NF-B drug, sodium salicylate, significantly blocked A-induced APOE promoter function. Our data provide evidence that upregulation of APOE by A in astroglial cells is mediated by an NF-B-element present in the 5'-flanking region of the APOE gene. (shrink)

Amyloid-beta peptide plaque in the brain is the primary diagnostic criterion of Alzheimer's disease . The physiological role of Abeta are poorly understood. We have previously determined an Abeta interacting domain in the promoters of AD-associated genes . This AbetaID interacts in a DNA sequence-specific manner with Abeta. We now demonstrate novel Abeta activity as a possible transcription factor. Herein, we detected Abeta-chromatin interaction in cell culture by ChIP assay. We observed that human neuroblastoma cells treated with FITC conjugated Abeta1-40 (...) localized Abeta to the nucleus in the presence of H2O2-mediated oxidative stress. Furthermore, primary rat fetal cerebrocortical cultures were transfected with APP and BACE1 promoter-luciferase fusions, and rat PC12 cultures were transfected with polymorphic APP promoter-CAT fusion clones. Transfected cells were treated with different Abeta peptides and/or H2O2. Abeta treatment of cell cultures produced a DNA sequence-specific response in cells transfected with polymorphic APP clones. Our results suggest the Abeta peptide may regulate its own production through feedback on its precursor protein and BACE1, leading to amyloidogenesis in AD. (shrink)

Employees perceive illegitimate tasks as inappropriate assignments because such tasks are beyond what they expect to do in any given job position. Extant literature indicates that, in addition to creating psychological strain and reducing well-being, illegitimate task assignments can result in counterproductive work behavior. This study extends the literature by examining whether illegitimate tasks may lead to two specific forms of CWB targeting organizations: destructive voice and time theft. To understand how and when this happens, we investigate the mediating role (...) of moral disengagement and the moderating role of psychological entitlement. Survey results based on 258 supervisor–subordinate dyads in China reveal that illegitimate tasks are positively related to destructive voice and time theft through moral disengagement. Furthermore, psychological entitlement strengthens the positive relationship between illegitimate tasks and moral disengagement and the indirect effect of illegitimate tasks on destructive voice and time theft. Overall, the findings provide insightful theoretical and managerial implications for research related to illegitimate tasks and CWB. (shrink)

Recent debates within the autism advocacy community have raised difficult questions about who can credibly act as a representative of a particular population and what responsibilities that...

Recognized as a simple communicative behavior, referential pointing is cognitively complex because it invites a communicator to consider an addressee's knowledge. Although we know referential pointing is affected by addressees’ physical location, it remains unclear whether and how communicators’ inferences about addressees’ mental representation of the interaction space influence sensorimotor control of referential pointing. The communicative perspective-taking task requires a communicator to point at one out of multiple referents either to instruct an addressee which one should be selected (communicative, COM) (...) or to predict which one the addressee will select (non-communicative, NCOM), based on either which referents can be seen (Level-1 perspective-taking, PT1) or how the referents were perceived (Level-2 perspective-taking, PT2) by the addressee. Communicators took longer to initiate the movements in PT2 than PT1 trials, and they held their pointing fingers for longer at the referent in COM than NCOM trials. The novel findings of this study pertain to trajectory control of the pointing movements. Increasing both communicative and perspective-taking demands led to longer pointing trajectories, with an under-additive interaction between those two experimental factors. This finding suggests that participants generate communicative behaviors that are as informative as required rather than overly exaggerated displays, by integrating communicative and perspective-taking information hierarchically during sensorimotor control. This observation has consequences for models of human communication. It implies that the format of communicative and perspective-taking knowledge needs to be commensurate with the movement dynamics controlled by the sensorimotor system. (shrink)

Joining the ongoing academic debates around medical students’ alternative career choices, this research examines the role of family in medical school attendees’ entrepreneurial intention. Specifically, this study decomposes the multidimensionality of family embeddedness and highlights the mediated nature of the family–EI relationship. The empirical analysis relied on data from graduation year medical students from diverse geographical locations and from different institution types in China. These data were collected from a total of 687 questionnaires covering the basic information of individual, parents, (...) and family composition, as well as the measuring scale of EI. Examining medical students’ EI and its antecedents provide a dual-missing-link in the extant knowledge, i.e., it adds the medical school piece to the overall picture of university students’ EI, and equally important, it de-trivializes entrepreneurship from the extant theorizations of medical students’ career choices. This study also bears implications for educators, practitioners, and policymakers interested in better understanding EI of medical school attendees and family embeddedness. (shrink)

Research shows that the effects of creative personality on moral disengagement and unethical behaviors are mixed. To reconcile the disparate findings, we draw on interdependence theory to unravel how and when creative personality is related to moral disengagement through countervailing pathways. Specifically, we propose competitive motivation and prosocial motivation as two distinct mechanisms that explain the double-edged effects of creative personality on moral disengagement and subsequent unethical behaviors. Furthermore, we hypothesize a cross-level moderating effect of competitive climate on the relationships (...) between competitive/prosocial motivation and moral disengagement. Results based on three-wave data from 753 employees showed that creative personality increased moral disengagement and subsequent unethical behaviors through competitive motivation but decreased moral disengagement and subsequent unethical behaviors through prosocial motivation. In addition, competitive climate weakened the negative relationship between prosocial motivation and moral disengagement and the negative indirect relationship between creative personality and unethical behaviors via prosocial motivation and moral disengagement. (shrink)

In the present study, we use a training design in two experiments to examine whether bilingual language switching facilitates two components of cognitive control, namely monitoring and inhibitory control. The results of Experiment 1 showed that training in language switching reduced mixing costs and the anti-saccade effect among bilinguals. In Experiment 2, the findings revealed a greater decrease of mixing costs and a smaller decrease of the anti-saccade effect from pre- to post-training for the language switching training group compared to (...) the L2 training group. Overall, the results suggest that extensive exercise in monitoring and inhibitory control among languages in an experimental setting may enhance the corresponding components of cognitive control. We discuss these findings in the context of the relationship between bilingual language control and executive control. (shrink)