Junctional complexes and cell polarity in the urinary tubule

In this review, we demonstrate how differentiated membrane domains can be detected in epithelial cells using conventional light and electron microscopy, freeze-fracture electron microscopy and the immunoand cytochemical detection of membrane components. Using specific examples from the kidney, we show how the polarized insertion of these components into either apical or basolateral plasma membrane regions on either side of the tight junction barrier is related to specific functions of principal and intercalated cells in the collecting duct. In addition, distinct basal and lateral membrane domains have been revealed in some cells that are maintained in the absence of a tight junctional barrier in the plane of the membrane. This suggests that other factors, possibly related to cytoskeletal elements, may be involved in the functional segregation of these membrane areas. We propose that epithelial cell plasma membranes should be subdivided into apical, lateral and basal regions, and that the term “basolateral” may be an oversimplification.     

The perceived effect of breakdown and repair on the performance of multiprocessor systems

It is argued that classical measures of computer system performance, for example mean response time, are inadequate in the context of fault-tolerant system design. Alternative, perception-based measures are proposed and theorems established describing their properties. Focus is directed upon the homogeneous M/M/m system in which total processor power is constrained by budget and processors are subject to failure and repair. A numerical technique for extracting both classical and perception-based measures from the associated two-dimensional Markov process is offered, along with bounds on time and space required for its execution. It is seen that the perception-based approach to system design can call for twice as many processors as the classical approach.     

Evidence for Oxidative Pathways in the Pathogenesis of PD: Are Antioxidants Candidate Drugs to Ameliorate Disease Progression?

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that arises due to a complex and variable interplay between elements including age, genetic, and environmental risk factors that manifest as the loss of dopaminergic neurons. Contemporary treatments for PD do not prevent or reverse the extent of neurodegeneration that is characteristic of this disorder and accordingly, there is a strong need to develop new approaches which address the underlying disease process and provide benefit to patients with this debilitating disorder. Mitochondrial dysfunction, oxidative damage, and inflammation have been implicated as pathophysiological mechanisms underlying the selective loss of dopaminergic neurons seen in PD. However, results of studies aiming to inhibit these pathways have shown variable success, and outcomes from large-scale clinical trials are not available or report varying success for the interventions studied. Overall, the available data suggest that further development and testing of novel therapies are required to identify new potential therapies for combating PD. Herein, this review reports on the most recent development of antioxidant and anti-inflammatory approaches that have shown positive benefit in cell and animal models of disease with a focus on supplementation with natural product therapies and selected synthetic drugs.     

A Study of Web Services Projects in the Financial Services Industry

This study examines the significance of technological, methodological, and business factors in contributing to the success of initial Web Services projects. Focusing on four case studies from the financial services sector, the authors' findings suggest that a strong focus on business factors is associated with successful Web Services strategies.     

A multi-institutional, multinational study of programming concepts using card sort data

Abstract: This paper presents a case study of the use of a repeated single‐criterion card sort with an unusually large, diverse participant group. The study, whose goal was to elicit novice programmers' knowledge of programming concepts, involved over 20 researchers from four continents and 276 participants drawn from 20 different institutions. In this paper we present the design of the study and the unexpected result that there were few discernible systematic differences in the population. The study was one of the activities of the National Science Foundation funded Bootstrapping Research in Computer Science Education project (2003).     

LXRα Regulates oxLDL-Induced Trained Immunity in Macrophages

Reprogramming of metabolic pathways in monocytes and macrophages can induce a proatherosclerotic inflammatory memory called trained innate immunity. Here, we have analyzed the role of the Liver X receptor (LXR), a crucial regulator of metabolism and inflammation, in oxidized low-density lipoprotein (oxLDL)-induced trained innate immunity. Human monocytes were incubated with LXR agonists, antagonists, and oxLDL for 24 h. After five days of resting time, cells were restimulated with the TLR-2 agonist Pam3cys. OxLDL priming induced the expression of LXRα but not LXRβ. Pharmacologic LXR activation was enhanced, while LXR inhibition prevented the oxLDL-induced inflammatory response. Furthermore, LXR inhibition blocked the metabolic changes necessary for epigenetic reprogramming associated with trained immunity. In fact, enrichment of activating histone marks at the IL-6 and TNFα promotor was reduced following LXR inhibition. Based on the differential expression of the LXR isoforms, we inhibited LXRα and LXRβ genes using siRNA in THP1 cells. As expected, siRNA-mediated knock-down of LXRα blocked the oxLDL-induced inflammatory response, while knock-down of LXRβ had no effect. We demonstrate a specific and novel role of the LXRα isoform in the regulation of oxLDL-induced trained immunity. Our data reveal important aspects of LXR signaling in innate immunity with relevance to atherosclerosis formation.     

Flexible electronics: Prediction of substrate deformation during different steps of the lithography process

A numerical model was developed to simulate the micro-deformations of a polymeric substrate due to lithographic processing of different layers of a transistor-like structure. The results of the model were validated with the results from experiments. The model, a mechanical-thermal-hygroscopic model, takes into account the dimensional effects of temperature, moisture and stresses. It also includes the temperature dependent visco-elastic behaviour of the polymer substrate. The model can be used to predict overlay accuracies between different functional layers introduced by the lithographic process. It can also be used to understand the underlying processes such that it provides a tool to improve the overlay accuracy during actual processing.     

Moderating effects of a craving intervention on the relation between negative mood and heavy drinking following treatment for alcohol dependence.

Objective: Negative affect is a significant predictor of alcohol relapse, and the relation between negative affect and drinking has been shown to be strongly mediated by alcohol craving. Thus, targeting craving during treatment could potentially attenuate the relation between negative affect and drinking. Method: The current study is a secondary analysis of data from the COMBINE study, a randomized clinical trial that combined pharmacotherapy with behavioral intervention in the treatment of alcohol dependence. Our goal in the current study was to examine whether a treatment module that targeted craving would predict changes in negative mood during the 16-week combined behavioral intervention (n = 776) and the relation among changes in mood, craving, and changes in heavy drinking during treatment and 1 year posttreatment. Results: Changes in negative mood were significantly associated with changes in heavy drinking during treatment (f2 = 0.78). Participants (n = 432) who received the craving module had significantly fewer heavy drinking days during treatment (d = 0.31), and receiving the module moderated the relation between negative mood and heavy drinking during treatment (f2 = 0.92) and 1 year posttreatment (f2 = 0.03). Moderating effects of the craving module were mediated by changes in craving during treatment. Within-subject analyses indicated significant pre- to postmodule reductions in negative mood. Additionally, postmodule craving significantly mediated the association between negative mood and heavy drinking during treatment and at posttreatment. Conclusions: The craving module of the combined behavioral intervention may weaken the relation between negative affect and heavy drinking by fostering greater decreases in craving during treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Consideration of the BDNF gene in relation to two phenotypes: Hoarding and obesity.

The gene coding for the brain derived neurotrophic factor (BDNF) has emerged as an interesting candidate for multiple brain and brain disorder-related phenomena. The primary aim of the present investigation was to consider the relationship between the BDNF Val66Met variant and two phenotypes: compulsive hoarding as a symptom dimension of obsessive–compulsive disorder (OCD), and body mass index (BMI). We examined the BDNF gene in a large (N = 301) clinical sample of probands with OCD. Participants were classified as hoarding or nonhoarding using a strict, multimeasure grouping approach. Results revealed that the Val/Val genotype was linked with hoarding classification and more severe hoarding behaviors, as well as greater BMI levels. Hoarding status was also associated with greater BMI scores, with individuals in the hoarding group being far more likely to be classified as obese compared with the nonhoarding group. Our findings may provide a distinct avenue through which hoarding and BMI could be linked. These findings are suggestive of a complex gene, body weight, and psychopathology relationship wherein a primitive, survival “thrifty gene” strategy may be conserved and represented in a subgroup of humans manifesting severe hoarding symptoms. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Testing the robustness of the dysphoria factor of the Simms et al. (2002) model of posttraumatic stress disorder.

The Simms et al. (2002) four-factor structure of posttraumatic stress disorder (PTSD) has been supported in many factor analytic studies, and the specificity of the dysphoria factor has been questioned because of its strong associations with measures of depression and anxiety. This study addressed this issue by conducting a confirmatory factor analysis while controlling for the symptoms of major depression (MD) and generalized anxiety disorder (GAD). Data from individuals who satisfied Criterion A of the diagnostic criteria for a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM–IV) diagnosis of PTSD (n = 12,467) in the 2004–2005 National Epidemiologic Study on Alcohol and Related Conditions (NESARC) were used in the analysis. The results showed that after controlling for MD and GAD, the factor loadings for dysphoria items were significantly attenuated, although they remained relatively high and statistically significant. The present findings contribute to the debate regarding how PTSD should be conceptualized and assessed in future issues of the DSM. (PsycINFO Database Record (c) 2011 APA, all rights reserved)