Noroviruses are major agents of viral gastroenteritis worldwide. The infectivity of Norwalk virus, the prototype norovirus, has been studied in susceptible human volunteers. A new variant of the hit theory model of microbial infection was developed to estimate the variation in Norwalk virus infectivity, as well as the degree of virus aggregation, consistent with independent (electron microscopic) observations. Explicit modeling of viral aggregation allows us to express virus infectivity per single infectious unit (particle). Comparison of a primary and a secondary inoculum showed that passage through a human host does not change Norwalk virus infectivity. We estimate the average probability of infection for a single Norwalk virus particle to be close to 0.5, exceeding that reported for any other virus studied to date. Infected subjects had a dose-dependent probability of becoming ill, ranging from 0.1 (at a dose of 10(3) NV genomes) to 0.7 (at 10(8) virus genomes). A norovirus dose response model is important for understanding its transmission and essential for development of a quantitative risk model. Norwalk virus is a valuable model system to study virulence because genetic factors are known for both complete and partial protection; the latter can be quantitatively described as heterogeneity in dose response models.

Prostate cancer is the most commonly diagnosed noncutaneous neoplasm and second most common cause of cancerrelated mortality in western men. To investigate the mechanisms of prostate cancer development and progression, we did expression profiling of human prostate cancer and benign tissues. We show that the SOX4 is overexpressed in prostate tumor samples compared with benign tissues by microarray analysis, real-time PCR, and immunohistochemistry. We also show that SOX4 expression is highly correlated with Gleason score at the mRNA and protein level using tissue microarrays. Genes affected by SOX4 expression were also identified, including BCL10, CSF1, and NcoA4/ARA70. TLE-1 and BBC3/PUMA were identified as direct targets of SOX4. Silencing of SOX4 by small interfering RNA transfection induced apoptosis of prostate cancer cells, suggesting that SOX4 could be a therapeutic target for prostate cancer. Stable transfection of SOX4 into nontransformed prostate cells enabled colony formation in soft agar, suggesting that, in the proper cellular context, SOX4 can be a transforming oncogene. (Cancer Res 2006; 66(8): 4011-9)

Disinfection is an essential measure for interrupting human norovirus (HuNoV) transmission, but it is difficult to evaluate the efficacy of disinfectants due to the absence of a practicable cell culture system for these viruses. The purpose of this study was to screen sodium hypochlorite and ethanol for efficacy against Norwalk virus (NV) and expand the studies to evaluate the efficacy of antibacterial liquid soap and alcohol-based hand sanitizer for the inactivation of NV on human finger pads. Samples were tested by real-time reverse transcription-quantitative PCR (RT-qPCR) both with and without a prior RNase treatment. In suspension assay, sodium hypochlorite concentrations of >160 ppm effectively eliminated RT-qPCR detection signal, while ethanol, regardless of concentration, was relatively ineffective, giving at most a 0.5 log 10 reduction in genomic copies of NV cDNA. Using the American Society for Testing and Materials (ASTM) standard finger pad method and a modification thereof (with rubbing), we observed the greatest reduction in genomic copies of NV cDNA with the antibacterial liquid soap treatment (0.67 to 1.20 log 10 reduction) and water rinse only (0.58 to 1.58 log 10 reduction). The alcohol-based hand sanitizer was relatively ineffective, reducing the genomic copies of NV cDNA by only 0.14 to 0.34 log 10 compared to baseline. Although the concentrations of genomic copies of NV cDNA were consistently lower on finger pad eluates pretreated with RNase compared to those without prior RNase treatment, these differences were not statistically significant. Despite the promise of alcohol-based sanitizers for the control of pathogen transmission, they may be relatively ineffective against the HuNoV, reinforcing the need to develop and evaluate new products against this important group of viruses.Human noroviruses (HuNoV) are the leading cause of acute nonbacterial gastroenteritis (11, 21). The U.S. Centers for Disease Control and Prevention estimate that approximately 23 million people suffer from HuNoV gastroenteritis each year. Indeed, 81% of outbreaks of nonbacterial gastroenteritis are caused by this agent (7,8). These viruses may contaminate food, water, hands, and inanimate surfaces and are readily transmitted by contact with contaminated objects, by consumption of fecally contaminated food or water, or between people. In particular, hands are thought to be a principal vehicle for HuNoV transmission. Although many different hand hygiene agents are available, these generally do not have specific virucidal claims against the HuNoV. Two widely used types of hand hygiene products are antibacterial liquid soaps and alcohol-based hand sanitizers.Little is known about the effectiveness of hand hygiene agents in reducing HuNoV on contaminated hands. One reason for this is that the HuNoV cannot be routinely cultured in vitro, a factor that complicates evaluation of the efficacy of disinfection strategies. As an alternative, investigators have used cultivable surrogates such as feline calicivirus (FCV) and murin...

Background: Essential hypertension is a common, polygenic, complex disorder resulting from interaction of several genes with each other and with environmental factors such as obesity, dietary salt intake, and alcohol consumption. Since the underlying genetic pathways remain elusive, currently most studies focus on the genes coding for proteins that regulate blood pressure as their physiological role makes them prime suspects.

We have performed whole genome expression profiling of 28 patient prostate tumor samples and 12 normal prostate samples and identified 55 upregulated and 60 downregulated genes significantly changed in prostate tumor samples compared to normal prostate tissues. Among the members of the upregulated gene set was the developmental transcription factor Homeobox C6 (HOXC6). Silencing of HOXC6 expression using small-interfering RNA (siRNA) resulted in decreased proliferation rates for both androgen-dependent LnCaP cells and the LnCaPderived androgen-independent C4-2 cell line. Flow cytometry and immunoblotting for the caspase-cleaved form of poly-ADP ribose polymerase (PARP) determined that the decrease in cell numbers was due to increased apoptosis. To validate the specificity of the siRNA-induced apoptosis, LnCaP cells were cotransfected with siRNA specific to the HOXC6 3 0 UTR and a mammalian expression vector containing the HOXC6 open reading frame, but lacking the 3 0 UTR. Overexpression of HOXC6 rescued the LnCaP cells from HOXC6 siRNA-induced apoptosis, and increased growth of control GFP siRNA-transfected cells. Expression profiling of HOXC6 siRNA transfections and HOXC6 overexpression identified neutral endopeptidase (NEP) and insulin-like growth factor binding protein-3 (IGFBP-3) as potential proapoptotic repression targets of HOXC6. Our data suggest that HOXC6 may be a novel potential therapeutic target for prostate cancer.

The estimated histories of migration and population growth indicated that patterns of HCV transmission differ among countries and viral subtypes.

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Silicone rubber foam was prepared through crosslinking with electron beam irradiation and foaming by the decomposing of blowing agent azobisformamide (AC) in hot air. The crosslinking and foaming of silicone rubber was carried out separately, which was different from the conventional method of chemical crosslinking and foaming. After foaming, the silicone rubber foam was irradiated again to stabilize the foam structure and further improve its mechanical properties. The effects of irradiation dose before and after foaming, and the amount of blowing agents on the structure and properties of silicone rubber foam were studied. The experimental results show that with the increase of AC content, the average cell diameter of silicone rubber foam increases a little, the foam density decreases to a minimum value when AC content is 10 phr. With the increase of irradiation dose before foaming from 10 to 17.5 kGy, the cell nucleation density of silicone rubber foam increases, the average cell diameter decreases, and the foam density increases. With the increase of irradiation before foaming, the tensile strength, tensile modulus, and the elongation at break of the silicone rubber foam increase. Through irradiation crosslinking again after foaming, the foam density is decreased and the mechanical properties of silicone foam are further improved.