84 resultados para T-Lymphocytes, Regulatory -- immunology


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A key problem in high dimensional anomaly detection is that the time spent in constructing detectors by the means of generateand-test is tolerable. In fact, due to the high sparsity. of the data, it is ineffective to construct detectors in the whole data space. Previous investigations have shown that most essentIal patterns can be discovered in different subspaces. This inspires us to construct detectors in signIficant subspaces only for anomaly detection. We first use ENCLUS-based method to discover all significant subspaces and .then use a greedy-growth algorithm to construct detectors in each subspace. The elements used to constItute a detector are gods Instead of data points, which makes the time-consumption irrelevant to the size of the nonnal data. We test the effectiveness and efficiency of our method on both synthetic and benchmark datasets. The results reveal that our method is particularly useful in anomaly detection in high dimensional data spaces.

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Intracellular zinc homeostasis is strictly regulated by zinc binding proteins and zinc transporters. In the present study, we quantified in a first global view the expression of all characterized human zinc exporters (hZnT-1-9) in different leukocyte subsets in response to zinc supplementation and depletion and analyzed their influence on alterations in the intracellular zinc concentration. We found that hZnT-1 is the most regulated zinc exporter. Furthermore, we discovered that hZnT-4 is localized in the plasma membrane similar to hZnT-1. hZnT-4 is most highly expressed in Molt-4, up-regulated after treatment with PHA and is responsible for the measured decrease of intracellular zinc content after high zinc exposure. In addition, we found that hZnT-5, hZnT-6, and hZnT-7 in Raji as well as hZnT-6 and hZnT-7 in THP-1 are up-regulated in response to cellular zinc depletion. Those zinc exporters are all localized in the Golgi network, and this type of regulation explains the observed zinc increase in both cell types after up-regulation of their expression during zinc deficiency and, subsequently, high zinc exposure. Furthermore, we detected, for the first time, the expression of hZnT-8 in peripheral blood lymphocytes, which varied strongly between individuals. While hZnT-2 was not detectable, hZnT-3 and hZnT-9 were expressed at low levels. Further on, the amount of expression was higher in primary cells than in cell lines. These data provide insight into the regulation of intracellular zinc homeostasis in cells of the immune system and may explain the variable effects of zinc deficiency on different leukocyte subsets.

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In an earlier paper, we adopted a bi-variate BEKK–GARCH framework and employed a systematic approach to examine structural breaks in the Hang Seng Index and Index Futures market volatility. Switching dummy variables were included and tested in the variance equations to check for any structural changes in the autoregressive volatility structure due to the events that have taken place in the Hong Kong market surrounding the Asian markets crisis. In this paper, we include measures of daily trading volume from both markets in the estimation. Likelihood ratio tests indicate the switching dummy variables become insignificant and the GARCH effects diminish but remain significant. There is some evidence that the Sequential Arrival of Information Model (SIM) provides a platform to explain these market induced effects when volume of trade is accounted for.

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Although CD8+ T cells do not contribute to protection against the blood stage of Plasmodium infection, there is mounting evidence that they are principal mediators of murine experimental cerebral malaria (ECM). At present, there is no direct evidence that the CD8+ T cells mediating ECM are parasite-specific or, for that matter, whether parasite-specific CD8+ T cells are generated in response to blood-stage infection. To resolve this and to define the cellular requirements for such priming, we generated transgenic P. berghei parasites expressing model T cell epitopes. This approach was necessary as MHC class I-restricted antigens to blood-stage infection have not been defined. Here, we show that blood-stage infection leads to parasite-specific CD8+ and CD4+ T cell responses. Furthermore, we show that P. berghei-expressed antigens are cross-presented by the CD8α+ subset of dendritic cells (DC), and that this induces pathogen-specific cytotoxic T lymphocytes (CTL) capable of lysing cells presenting antigens expressed by blood-stage parasites. Finally, using three different experimental approaches, we provide evidence that CTL specific for parasite-expressed antigens contribute to ECM.

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The gene for Rhotekin 2 (RTKN2) was originally identified in a promyelocytic cell line resistant to oxysterol-induced apoptosis. It is differentially expressed in freshly isolated CD4+ T-cells compared with other hematopoietic cells and is down-regulated following activation of the T-cell receptor. However, very little is known about the function of RTKN2 other than its homology to Rho-GTPase effector, rhotekin, and the possibility that they may have similar roles. Here we show that stable expression of RTKN2 in HEK cells enhanced survival in response to intrinsic apoptotic agents; 25-hydroxy cholesterol and camptothecin, but not the extrinsic agent, TNFα. Inhibitors of NF-KappaB, but not MAPK, reversed the resistance and mitochondrial pro-apoptotic genes, Bax and Bim, were down regulated. In these cells, there was no evidence of RTKN2 binding to the GTPases, RhoA or Rac2. Consistent with the role of RTKN2 in HEK over-expressing cells, suppression of RTKN2 in primary human CD4+ T-cells reduced viability and increased sensitivity to 25-OHC. The expression of the pro-apoptotic genes, Bax and Bim were increased while BCL-2 was decreased. In both cell models RTKN2 played a role in the process of intrinsic apoptosis and this was dependent on either NF-KappaB signaling or expression of downstream BCL-2 genes. As RTKN2 is a highly expressed in CD4+ T-cells it may play a role as a key signaling switch for regulation of genes involved in T-cell survival.

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Why is it that some people respond in a more negative way to procedural injustice than do others, and why is it that some people go on to defy authority while others in the same situation do not? Personality theorists suggest that the psychological effect of a situation depends on how a person interprets the situation and that such differences in interpretation can vary as a function of individual difference factors. For example, affect intensity—one’s predisposition to react more or less emotionally to an event—is one such individual difference factor that has been shown to influence people’s reactions to events. Cross-sectional survey data collected from (a) 652 tax offenders who have been through a serious law enforcement experience (Study 1), and (b) 672 citizens with recent personal contact with a police officer (Study 2), showed that individual differences in ‘affect intensity’ moderate the effect of procedural justice on both affective reactions and compliance behavior. Specifically, perceptions of procedural justice had a greater effect in reducing anger and reports of non-compliance among those lower in affect intensity than those higher in affect intensity. Both methodological and theoretical explanations are offered to explain the results, including the suggestion that emotions of shame may play a role in the observed interaction.

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Procedural justice generally enhances an authority's legitimacy and encourages people to comply with an authority's decisions and rules. We argue, however, that previous research on procedural justice and legitimacy has examined legitimacy in a limited way by focusing solely on the perceived legitimacy of authorities and ignoring how people may perceive the legitimacy of the laws and rules they enforce. In addition, no research to date has examined how such perceptions of legitimacy may moderate the effect of procedural justice on compliance behavior. Using survey data collected across three different regulatory contexts – taxation (Study 1), social security (Study 2), and law enforcement (Study 3) – the findings suggest that one's perceptions of the legitimacy of the law moderates the effect of procedural justice on compliance behaviors; procedural justice is more important for shaping compliance behaviors when people question the legitimacy of the laws than when they accept them as legitimate. An explanation of these findings using a social distancing framework is offered, along with a discussion of the implications the findings have on enforcement.

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The building project development approval proces is increasingly complex and farught with conflict due to the rise of the sustainable urban development movement and inclusive decision making.  Coupled with this, government decision-making decentralisation has resulted in a fragmented and over-regulated compliance sytem.  Problems arising from the process include wated resources, excessive time delays, increased holding and litigation costs, inadequate planning coorindation, high lelves of advocacy costs and a divisive a politicised approval prcess.

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The purpose of this commentary is to consider the extent to which food regulatory systems protect public health, and how a better job could be done. There are fundamental questions about the role of food regulations in responding to changes in food systems and to food-related public health issues. What is meant by the objective ‘to protect public health and safety’ in the context of food regulation? Are current systems well balanced between promoting trade and protecting health? What is the role of nutrition in food regulation? Should food regulation be used to promote as well as to protect public health? Should laws and regulations be used to intervene in the formulation and marketing of foods, or should ‘the market’ merely provide more choices and information for shoppers and consumers to select healthy diets?

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Why do some entrepreneurs succeed while others fail in international competition? Perhaps it is better to turn the question around and ask, why is it that a particular country or economy becomes the home base for competitive globally-oriented entrepreneurs? What makes Australia a global leader in wine exports? How did New Zealand make it to global ranks in the creative industries? Why does Singapore have the most businessfriendly environment for entrepreneurs? Why is it “location, location, location”? One of the most powerful factors is the regulatory environment.

Asia-Pacific country-specific and region-specific regulations are diverse, and they seriously affect the climate for start-up entrepreneurs. They range from best-in-the world (e.g. Australia, New Zealand and Singapore) to the dreadful (Indonesia), according to the World Bank. Costs and profits can be affected as much by a government regulation as by a management decision. Fundamental entrepreneurial decisions--such as which lines of business to go into, which products and services to produce and introduce, which investments to finance, how and where to make goods and how to market them, and what prices to charge--are increasingly subject to governmental control.

In this short paper, we examine World Bank and Transparency International data on Asia-Pacific regulatory environments and make statements about how the economies compare to best practice. While I use data collected by other sources, I believe the added value comes through comparing and contrast the regulatory environments of our region in a justifiable and easily understood manner.