Differential effects of kynurenine and tryptophan treatment on quinolinate immunoreactivity in rat lymphoid and non-lymphoid organs

Quinolinate is a tryptophan metabolite and an intermediary in nicotinamide adenine dinucleotide (NAD+) synthesis in hepatocytes. Kynurenine is an upstream metabolite in the same biochemical pathway. Under normal physiological conditions, kynurenine is thought to be produced primarily in the liver as an NAD+ precursor. However, during immune stimulation or inflammation, numerous extrahepatic tissues convert systemic tryptophan to kynurenine, and its concentration subsequently rises dramatically in blood. The fate and role of extrahepatic kynurenine are uncertain. In order to begin addressing this question, the present study was performed to determine which cell types can produce quinolinate from either systemic tryptophan or kynurenine. By using highly specific antibodies to protein-coupled quinolinate, we found that intraperitoneal injections of tryptophan led to increased quinolinate immunoreactivity primarily in hepatocytes, with moderate increases in tissue macrophages and splenic follicles. In contrast, intraperitoneal injections of kynurenine did not result in any significant increase in hepatocyte quinolinate immunoreactivity, but rather led to dramatic increases in immunoreactivity in tissue macrophages, splenic white pulp, and thymic medulla. These findings suggest that hepatocytes do not make significant use of extracellular kynurenine for quinolinate or NAD+ synthesis, and that, instead, extrahepatic kynurenine is preferentially metabolized by immune cells throughout the body. The possible significance of the preferential metabolism of kynurenine by immune cells during an immune response is discussed.     

Experimental designs in which each subject is used repeatedly.

Illustrates the fact that in many fields of research, the investigator makes use of experiments in which the same experimental unit (s) is used repeatedly. 1 of the main problems such experiments pose for the researcher is that the observations may not be all statistically independent. In the recent literature, reviewed in this article, several particular forms of statistical dependence between successive observations on the same s have been conceptualized, and the appropriate designs and modes of analysis have been derived. (28 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Object and Action Classification with Latent Window Parameters

In this paper we propose a generic framework to incorporate unobserved auxiliary information for classifying objects and actions. This framework allows us to automatically select a bounding box and its quadrants from which best to extract features. These spatial subdivisions are learnt as latent variables. The paper is an extended version of our earlier work Bilen et al. (Proceedings of The British Machine Vision Conference, 2011), complemented with additional ideas, experiments and analysis. We approach the classification problem in a discriminative setting, as learning a max-margin classifier that infers the class label along with the latent variables. Through this paper we make the following contributions: (a) we provide a method for incorporating latent variables into object and action classification; (b) these variables determine the relative focus on foreground versus background information that is taken account of; (c) we design an objective function to more effectively learn in unbalanced data sets; (d) we learn a better classifier by iterative expansion of the latent parameter space. We demonstrate the performance of our approach through experimental evaluation on a number of standard object and action recognition data sets.     

Lovastatin and phenylacetate inhibit the induction of nitric oxide synthase and cytokines in rat primary astrocytes, microglia, and macrophages

This study explores the role of mevalonate inhibitors in the activation of NF-kbeta and the induction of inducible nitric oxide synthase (iNOS) and cytokines (TNF-alpha, IL-1beta, and IL-6) in rat primary astrocytes, microglia, and macrophages. Lovastatin and sodium phenylacetate (NaPA) were found to inhibit LPS- and cytokine-mediated production of NO and expression of iNOS in rat primary astrocytes; this inhibition was not due to depletion of end products of mevalonate pathway (e.g., cholesterol and ubiquinone). Reversal of the inhibitory effect of lovastatin on LPS-induced iNOS expression by mevalonate and farnesyl pyrophosphate and reversal of the inhibitory effect of NaPA on LPS-induced iNOS expression by farnesyl pyrophosphate, however, suggests a role of farnesylation in the LPS-mediated induction of iNOS. The inhibition of LPS-mediated induction of iNOS by FPT inhibitor II, an inhibitor of Ras farnesyl protein transferase, suggests that farnesylation of p21(ras) or other proteins regulates the induction of iNOS. Inhibition of LPS-mediated activation of NF-kbeta by lovastatin, NaPA, and FPT inhibitor II in astrocytes indicates that the observed inhibition of iNOS expression is mediated via inhibition of NF-kbeta activation. In addition to iNOS, lovastatin and NaPA also inhibited LPS-induced expression of TNF-alpha, IL-1beta, and IL-6 in rat primary astrocytes, microglia, and macrophages. This study delineates a novel role of the mevalonate pathway in controlling the expression of iNOS and different cytokines in rat astrocytes, microglia, and macrophages that may be important in developing therapeutics against cytokine- and NO-mediated neurodegenerative diseases.     

New Method for Measuring the Safety Risk of Construction Activities: Task Demand Assessment

The task demand assessment (TDA) is a new technique for measuring the safety risk of construction activities and analyzing how changes in operation parameters can affect the potential for accidents. TDA is similar to observational ergonomic methods—it does not produce estimates of probabilities of incidents, but it quantifies the “task demand” of actual operations based on characteristics of the activity and independent of the workers’ capabilities. The task demand reflects the difficulty to perform the activity safely. It is based on (1) the exposure to a hazard and (2) the presence and level of observable task demand factors—that is, risk factors that can increase the potential for an accident. The paper presents the findings from the initial implementation of TDA and demonstrates its feasibility and applicability on two different operations: a roofing activity and a concrete paving operation. Furthermore, the paving case illustrates how the TDA method can compare different production scenarios and measure the effect of production variables on the accident potential. The findings indicate that the method can be applied on activities of varying complexity and can account for several risks and task demand factors as required by the user. The selection of task demand factors is a key issue for the validity of the method and requires input from the crew and safety management. The limitations of the methodology and the need for further research are discussed. Overall, TDA provides a tool that can assist researchers and practitioners in the analysis and design of construction operations.     

The lithium—thionyl chloride battery — a review

The lithium—thionyl chloride nonaqueous cell system is a recent development. Low atomic weight and high electrode potential make lithium unique as an anode in energy devices. Preparation of the anode, cathode, and the electrolyte is reviewed. The construction of the cell, its performance characteristics, uses, etc., are also surveyed.     

Cognitive Approach to Construction Safety: Task Demand-Capability Model

In the evolution of safety research, the literature identifies three paradigms: normative, error-based, and cognitive engineering. Traditionally, strategies to improve construction safety have been based on the normative paradigm—compliance with prescribed safety rules. However, the normative approach ignores how the characteristics of the production system and team processes influence the work behaviors and the possibility of errors and accidents. These factors are the focus of the cognitive engineering perspective. This study develops a cognitive model of construction safety, which conceptualizes safety as an emergent property of the production system. The model proposes that during a task, the task demands and the applied capabilities determine the potential for errors and accidents. It also proposes that the production practices and the teamwork processes of the crew shape the work situations that the workers face—that is, the task demands and the applied capability. Empirical evidence from recent case studies is discussed. The cognitive perspective shifts the focus of accident prevention from conformance with rules to the issues of task demands and applied capabilities, and the factors affecting them—such as work design, workload, resource allocation, and team processes.