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)

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)

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)

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)

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)

The X-ray and bulk densities of PdIn alloys have been determined at ambient temperature on samples annealed at 1273 and 1373 K and quenched in water-ice mixtures. From these measurements the vacancy concentrations in this intermetallic phase have been obtained as a function of In concentration at these two temperatures. In addition, a generalized thermodynamic model is presented which considers the existence of antisite and vacancy defects on both sublattices without any dilute solution approximations. This model uses three energy parameters, (...) whose values have been obtained for PdIn using the measured vacancy concentrations and the chemical potentials of In. This model is able to describe all the available vacancy data and is suitable for calculating these values at compositions and temperatures when such data are not available. In addition, the model permits the calculation of the concentrations of the minority point defects. It is shown that dilute-solution approximations, which have invariably been used in this kind of modelling, are unsatisfactory. The present results and their analysis confirm that PdIn is a near-triple-defect type of intermetallic and not a near-Schottky type, as has been claimed recently. (shrink)

Peter Abelard (1079–1142 ce) was the most wide‐ranging philosopher of the twelfth century. He quickly established himself as a leading teacher of logic in and near Paris shortly after 1100. After his affair with Heloise, and his subsequent castration, Abelard became a monk, but he returned to teaching in the Paris schools until 1140, when his work was condemned by a Church Council at Sens. His logical writings were based around discussion of the “Old Logic”: Porphyry's Isagoge, aristotle'S Categories and (...) On Interpretation and boethius'S textbook on topical inference. They comprise a freestanding Dialectica (“Logic”; probably c.1116), a set of commentaries (known as the Logica [Ingredientibus], c. 1119) and a later (c. 1125) commentary on the Isagoge (Logica Nostrorum Petititoni Sociorum or Glossulae). In a work Abelard called his Theologia, issued in three main versions (between 1120 and c.1134), he attempted a logical analysis of trinitarian relations and explored the philosophical problems surrounding God's claims to omnipotence and omniscience. The Collationes (“Debates,” also known as “Dialogue between a Christian, a Philosopher and a Jew”; probably c.1130) present a rational investigation into the nature of the highest good, in which the Christian and the Philosopher (who seems to be modeled on a philosopher of pagan antiquity) are remarkably in agreement. The unfinished Scito teipsum (“Know thyself,” also known as the “Ethics”; c.1138) analyses moral action. (shrink)

Let ≤r and ≤sbe two binary relations on 2ℕ which are meant as reducibilities. Let both relations be closed under finite variation and consider the uniform distribution on 2ℕ, which is obtained by choosing elements of 2ℕ by independent tosses of a fair coin.Then we might ask for the probability that the lower ≤r-cone of a randomly chosen set X, that is, the class of all sets A with A ≤rX, differs from the lower ≤s-cone of X. By c osure (...) under finite variation, the Kolmogorov 0-1 aw yields immediately that this probability is either 0 or 1; in case it is 1, the relations are said to be separable by random oracles.Again by closure under finite variation, for every given set A, the probability that a randomly chosen set X is in the upper ≤r-cone of A is either 0 or 1; let Almostr be the class of sets for which the upper ≤r-cone has measure 1. In the following, results about separations by random oracles and about Almost classes are obtained in the context of generalized reducibilities, that is, for binary relations on 2ℕ which can be defined by a countable set of total continuous functionals on 2ℕ in the same way as the usual resource-bounded reducibilities are defined by an enumeration of appropriate oracle Turing machines. The concept of generalized reducibility comprises a natura resource-bounded reducibilities, but is more general; in particular, it does not involve any kind of specific machine model or even effectivity. The results on generalized reducibilities yield corollaries about specific resource-bounded reducibilities, including several results which have been shown previously in the setting of time or space bounded Turing machine computations. (shrink)

Although the same environmental regulations apply to all regions in China, legal enforcement can be different due to local economic development priorities. There is still a lack of knowledge about how regional disparities affect the operating performance results of the implementation of corporate environmental management practices, thus providing little information for foreign companies when they invest and develop their production base in China. To fill this research gap, this paper collects data from the Fortune 500 Chinese firms to investigate the (...) moderating role of regional disparities in affecting the performance results of corporate environmental management efforts based on the institutional theory. The disclosed corporate environmental responsibility practices serve as proxy to represent corporate environmental management practices. Content analysis approach was applied to collect and analyze CER practices published in the corporate reports of Chinese manufacturers. The results show that CER has a positive impact on operating income, while regional disparities influence the relationship between CER and corporate operating income. Specifically, CER and operating income are positively related in Eastern China; on the contrary, they are negatively related in Western China. This paper adds to the body of knowledge about environmental discrepancies in the same emerging economy, and provides insights for systematic consideration in terms of the issues of government environmental regulations and corporate environmental strategies. (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)

ABSTRACTThe rapid expansion of primary education in Ethiopia has enabled most children to attend primary education—or at least to start schooling. This expansion, however, is largely “symbolic” rat...

Mitigating response distortion in answers to sensitive questions is an important issue for business ethics researchers. Sensitive questions may be asked in surveys related to business ethics, and respondents may intend to avoid exposing sensitive aspects of their character by answering such questions dishonestly, resulting in response distortion. Previous studies have provided evidence that a surveying procedure called the randomized response technique is useful for mitigating such distortion. However, previous studies have mainly applied the RRT to individual dichotomous questions in (...) face-to-face survey settings. In this study, we focus on behavioral research examining the relationships between latent variables, which are unobserved variables measured by multiple items on Likert or bipolar scales. To demonstrate how the RRT can be applied to obtain valid answers from respondents answering a self-administered online questionnaire with Likert and bipolar scales, we build a behavioral model to study the effect of punishment severity on employees’ attitudes toward misuse of information systems resources in the workplace, which in turn influence misuse behavior. The survey findings meet our expectations. The respondents are generally more willing to disclose sensitive data about their attitudes and actual behavior related to misuse when the RRT is implemented. The RRT’s implications for causal modeling and the advantages and challenges of its use in online environments are also discussed. (shrink)