23 research outputs found

    Highly chlorinated PCBs inhibit the human xenobiotic response mediated by the steroid and xenobiotic receptor (SXR).

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    Polychlorinated biphenyls (PCBs) are a family of persistent organic contaminants suspected to cause adverse effects in wildlife and humans. In rodents, PCBs bind to the aryl hydrocarbon (AhR) and pregnane X receptors (PXR) inducing the expression of catabolic cytochrome p450 enzymes of the CYP1A and 3A families. We found that certain highly chlorinated PCBs are potent activators of rodent PXR but antagonize its human ortholog, the steroid and xenobiotic receptor (SXR), inhibiting target gene induction. Thus, exposure to PCBs may blunt the human xenobiotic response, inhibiting the detoxification of steroids, bioactive dietary compounds, and xenobiotics normally mediated by SXR. The antagonistic PCBs are among the most stable and abundant in human tissues. These findings have important implications for understanding the biologic effects of PCB exposure and the use of animal models to predict the attendant risk

    The steroid and xenobiotic receptor (SXR), beyond xenobiotic metabolism

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    The steroid and xenobiotic receptor (SXR) (also known as pregnane X receptor or PXR) is a nuclear hormone receptor activated by a diverse array of endogenous hormones, dietary steroids, pharmaceutical agents, and xenobiotic compounds. SXR has an enlarged, flexible, hydrophobic ligand binding domain (LBD) which is remarkably divergent across mammalian species and SXR exhibits considerable differences in its pharmacology among mammals. The broad response profile of SXR has led to the development of "the steroid and xenobiotic sensor hypothesis". SXR has been established as a xenobiotic sensor that coordinately regulates xenobiotic clearance in the liver and intestine via induction of genes involved in drug and xenobiotic metabolism. In the past few years, research has revealed new and mostly unsuspected roles for SXR in modulating inflammation, bone homeostasis, vitamin D metabolism, lipid homeostasis, energy homeostasis and cancer. The identification of SXR as a xenobiotic sensor has provided an important tool for studying new mechanisms through which diet, chemical exposure, and environment ultimately impact health and disease. The discovery and pharmacological development of new PXR modulators might represent an interesting and innovative therapeutic approach to combat various diseases

    A ROBUST PCT METHOD BASED ON COMPLEX LEAST SQUARES ADJUSTMENT METHOD

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    Polarization Coherence Tomography (PCT) method has the good performance in deriving the vegetation vertical structure. However, Errors caused by temporal decorrelation and vegetation height and ground phase always propagate to the data analysis and contaminate the results. In order to overcome this disadvantage, we exploit Complex Least Squares Adjustment Method to compute vegetation height and ground phase based on Random Volume over Ground and Volume Temporal Decorrelation (RVoG + VTD) model. By the fusion of different polarimetric InSAR data, we can use more observations to obtain more robust estimations of temporal decorrelation and vegetation height, and then, we introduce them into PCT to acquire more accurate vegetation vertical structure. Finally the new approach is validated on E-SAR data of Oberpfaffenhofen, Germany. The results demonstrate that the robust method can greatly improve accusation of vegetation vertical structure

    NoPSM: A Concurrent MAC Protocol over Low-Data-Rate Low-Power Wireless Channel without PRR-SINR Model

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    Concurrent MAC protocols can improve channel usage of wireless sensor networks (WSNs), and provide a high-performance infrastructure for data intensive applications. Most of the existing concurrent MAC protocols are based on proactively constructed physical interference models, i.e., PRR-SINR models (PSM). However, it incurs relatively high bandwidth and energy overheads to construct PSM for WSNs. In this paper, we propose NoPSM, which does not take PSM as base to determine transmission concurrency. Instead, the base of NoPSM is reactively constructed interference relationships by passively analyzing overlapping relationships among time logs of block data transmissions and corresponding reception status of each packet in blocks. In this way, NoPSM has two salient features. First, NoPSM is able to construct interference relationships among nodes quickly and accurately along with block data transmissions without needs of network downtime. Second, based on the constructed interference relationships, NoPSM can make decisions of transmission concurrency with a comprehensive criterion, which not only estimates quality of any active links after initiating a new link, but also estimates throughput improvement gained from concurrent transmissions. NoPSM has been implemented in Tinyos-2.1 and extensively evaluated in TOSSIM. Experimental results show that NoPSM improves system throughput by up to 60 percent compared with a traditional CSMA protocol, which cannot exploit potential transmission concurrency. Moreover, NoPSM can gain up to 55 percent throughput improvement as compared to an existing reactive concurrent MAC
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