Increased Rate of Hospitalization for Diabetes and Residential Proximity of Hazardous Waste Sites

BACKGROUND: Epidemiologic studies suggest that there may be an association between environmental exposure to persistent organic pollutants (POPs) and diabetes. OBJECTIVE: The aim of this study was to test the hypothesis that residential proximity to POP-contaminated waste sites result in increased rates of hospitalization for diabetes. METHODS: We determined the number of hospitalized patients 25–74 years of age diagnosed with diabetes in New York State exclusive of New York City for the years 1993–2000. Descriptive statistics and negative binomial regression were used to compare diabetes hospitalization rates in individuals who resided in ZIP codes containing or abutting hazardous waste sites containing POPs (“POP” sites); ZIP codes containing hazardous waste sites but with wastes other than POPs (“other” sites); and ZIP codes without any identified hazardous waste sites (“clean” sites). RESULTS: Compared with the hospitalization rates for diabetes in clean sites, the rate ratios for diabetes discharges for people residing in POP sites and “other” sites, after adjustment for potential confounders were 1.23 [95% confidence interval (CI), 1.15–1.32] and 1.25 (95% CI, 1.16–1.34), respectively. In a subset of POP sites along the Hudson River, where there is higher income, less smoking, better diet, and more exercise, the rate ratio was 1.36 (95% CI, 1.26–1.47) compared to clean sites. CONCLUSIONS: After controlling for major confounders, we found a statistically significant increase in the rate of hospitalization for diabetes among the population residing in the ZIP codes containing toxic waste sites

WW domain-mediated interaction with Wbp2 is important for the oncogenic property of TAZ

The transcriptional co-activators YAP and TAZ are downstream targets inhibited by the Hippo tumor suppressor pathway. YAP and TAZ both possess WW domains, which are important protein–protein interaction modules that mediate interaction with proline-rich motifs, most commonly PPXY. The WW domains of YAP have complex regulatory roles as exemplified by recent reports showing that they can positively or negatively influence YAP activity in a cell and context-specific manner. In this study, we show that the WW domain of TAZ is important for it to transform both MCF10A and NIH3T3 cells and to activate transcription of ITGB2 but not CTGF, as introducing point mutations into the WW domain of TAZ (WWm) abolished its transforming and transcription-promoting ability. Using a proteomic approach, we discovered potential regulatory proteins that interact with TAZ WW domain and identified Wbp2. The interaction of Wbp2 with TAZ is dependent on the WW domain of TAZ and the PPXY-containing C-terminal region of Wbp2. Knockdown of endogenous Wbp2 suppresses, whereas overexpression of Wbp2 enhances, TAZ-driven transformation. Forced interaction of WWm with Wbp2 by direct C-terminal fusion of full-length Wbp2 or its TAZ-interacting C-terminal domain restored the transforming and transcription-promoting ability of TAZ. These results suggest that the WW domain-mediated interaction with Wbp2 promotes the transforming ability of TAZ

Update on the Risk of Hepatocellular Carcinoma in Chronic Hepatitis B Virus Infection

Chronic hepatitis B virus infection is an important cause of liver-related morbidity and mortality, with hepatocellular carcinoma being the most life-threatening complication. Because of the highly variable clinical course of the disease, enormous research efforts have been made with the aim of revealing the factors in the natural history that are relevant to hepatocarcinogenesis. These include epidemiological studies of predisposing risk groups, viral studies of mutations within the hepatitis B viral genome, and clinical correlation of these risk factors in predicting the likelihood of development of hepatocellular cancer in susceptible hosts. This update addresses these risks, with emphasis on the latest research relevant to hepatocarcinogenesis

FastTagger: an efficient algorithm for genome-wide tag SNP selection using multi-marker linkage disequilibrium

<p>Abstract</p> <p>Background</p> <p>Human genome contains millions of common single nucleotide polymorphisms (SNPs) and these SNPs play an important role in understanding the association between genetic variations and human diseases. Many SNPs show correlated genotypes, or linkage disequilibrium (LD), thus it is not necessary to genotype all SNPs for association study. Many algorithms have been developed to find a small subset of SNPs called tag SNPs that are sufficient to infer all the other SNPs. Algorithms based on the <it>r</it>²LD statistic have gained popularity because <it>r</it>²is directly related to statistical power to detect disease associations. Most of existing <it>r</it>²based algorithms use pairwise LD. Recent studies show that multi-marker LD can help further reduce the number of tag SNPs. However, existing tag SNP selection algorithms based on multi-marker LD are both time-consuming and memory-consuming. They cannot work on chromosomes containing more than 100 k SNPs using length-3 tagging rules.</p> <p>Results</p> <p>We propose an efficient algorithm called FastTagger to calculate multi-marker tagging rules and select tag SNPs based on multi-marker LD. FastTagger uses several techniques to reduce running time and memory consumption. Our experiment results show that FastTagger is several times faster than existing multi-marker based tag SNP selection algorithms, and it consumes much less memory at the same time. As a result, FastTagger can work on chromosomes containing more than 100 k SNPs using length-3 tagging rules.</p> <p>FastTagger also produces smaller sets of tag SNPs than existing multi-marker based algorithms, and the reduction ratio ranges from 3%-9% when length-3 tagging rules are used. The generated tagging rules can also be used for genotype imputation. We studied the prediction accuracy of individual rules, and the average accuracy is above 96% when <it>r</it>²≥ 0.9.</p> <p>Conclusions</p> <p>Generating multi-marker tagging rules is a computation intensive task, and it is the bottleneck of existing multi-marker based tag SNP selection methods. FastTagger is a practical and scalable algorithm to solve this problem.</p

Synthesis of Heterogeneous Li4Ti5O12 Nanostructured Anodes with Long-Term Cycle Stability

The 0D-1D Lithium titanate (Li4Ti5O12) heterogeneous nanostructures were synthesized through the solvothermal reaction using lithium hydroxide monohydrate (Li(OH)·H2O) and protonated trititanate (H2Ti3O7) nanowires as the templates in an ethanol/water mixed solvent with subsequent heat treatment. A scanning electron microscope (SEM) and a high resolution transmission electron microscope (HRTEM) were used to reveal that the Li4Ti5O12 powders had 0D-1D heterogeneous nanostructures with nanoparticles (0D) on the surface of wires (1D). The composition of the mixed solvents and the volume ratio of ethanol modulated the primary particle size of the Li4Ti5O12 nanoparticles. The Li4Ti5O12 heterogeneous nanostructures exhibited good capacity retention of 125 mAh/g after 500 cycles at 1C and a superior high-rate performance of 114 mAh/g at 20C

Exogenous interleukin-6, interleukin-13, and interferon-gamma provoke pulmonary abnormality with mild edema in enterovirus 71-infected mice

<p>Abstract</p> <p>Background</p> <p>Neonatal mice developed neurological disease and pulmonary dysfunction after an infection with a mouse-adapted human Enterovirus 71 (EV71) strain MP4. However, the hallmark of severe human EV71 infection, pulmonary edema (PE), was not evident.</p> <p>Methods</p> <p>To test whether EV71-induced PE required a proinflammatory cytokine response, exogenous pro-inflammatory cytokines were administered to EV71-infected mice during the late stage of infection.</p> <p>Results</p> <p>After intracranial infection of EV71/MP4, 7-day-old mice developed hind-limb paralysis, pulmonary dysfunction, and emphysema. A transient increase was observed in serum IL-6, IL-10, IL-13, and IFN-γ, but not noradrenaline. At day 3 post infection, treatment with IL-6, IL-13, and IFN-γ provoked mild PE and severe emphysema that were accompanied by pulmonary dysfunction in EV71-infected, but not herpes simplex virus-1 (HSV-1)-infected control mice. Adult mice did not develop PE after an intracerebral microinjection of EV71 into the nucleus tractus solitarii (NTS). While viral antigen accumulated in the ventral medulla and the NTS of intracerebrally injected mice, neuronal loss was observed in the ventral medulla only.</p> <p>Conclusions</p> <p>Exogenous IL-6, IL-13, and IFN-γ treatment could induce mild PE and exacerbate pulmonary abnormality of EV71-infected mice. However, other factors such as over-activation of the sympathetic nervous system may also be required for the development of classic PE symptoms.</p

Characteristics of pncA mutations in multidrug-resistant tuberculosis in Taiwan

<p>Abstract</p> <p>Background</p> <p>Pyrazinamide (PZA) is an important first-line drug in multidrug-resistant tuberculosis (MDRTB) treatment. However, the unreliable results obtained from traditional susceptibility testing limits its usefulness in clinical settings. The detection of <it>pncA </it>gene mutations is a potential surrogate of PZA susceptibility testing, especially in MDRTB isolates. The impact of genotypes of <it>M. tuberculosis </it>in <it>pncA </it>gene mutations also remains to be clarified.</p> <p>Methods</p> <p>MDRTB isolates were collected from six hospitals in Taiwan from January 2007 to December 2009. <it>pncA </it>gene sequencing, pyrazinamidase activity testing, and spoligotyping were performed on all of the isolates. PZA susceptibility was determined by the BACTEC MGIT 960 PZA method. The sensitivity and specificity of <it>pncA </it>gene analysis were estimated based on the results of PZA susceptibility testing.</p> <p>Results</p> <p>A total of 66 MDRTB isolates, including 37 Beijing and 29 non-Beijing strains, were included for analysis. Among these isolates, 36 (54.5%) were PZA-resistant and 30 (45.5%) were PZA-susceptible. The PZA-resistant isolates were more likely to have concomitant resistance to ethambutol and streptomycin. Thirty-seven mutation types out of 30 isolates were identified in the <it>pncA </it>gene, and most of them were point mutations. The sensitivities of <it>pncA </it>gene sequencing for PZA susceptibility in overall isolates, Beijing and non-Beijing strains were 80.6%, 76.2%, and 86.7% respectively, and the specificities were 96.7%, 93.8%, and 100% respectively.</p> <p>Conclusions</p> <p>More than half of the MDRTB isolates in this study are PZA-resistant. Analysis of <it>pncA </it>gene mutations helped to identify PZA-susceptible MDRTB isolates, especially in non-Beijing strains.</p

A Long Baseline Neutrino Oscillation Experiment Using J-PARC Neutrino Beam and Hyper-Kamiokande

Document submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresDocument submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresDocument submitted to 18th J-PARC PAC meeting in May 2014. 50 pages, 41 figuresHyper-Kamiokande will be a next generation underground water Cherenkov detector with a total (fiducial) mass of 0.99 (0.56) million metric tons, approximately 20 (25) times larger than that of Super-Kamiokande. One of the main goals of Hyper-Kamiokande is the study of $CP$ asymmetry in the lepton sector using accelerator neutrino and anti-neutrino beams. In this document, the physics potential of a long baseline neutrino experiment using the Hyper-Kamiokande detector and a neutrino beam from the J-PARC proton synchrotron is presented. The analysis has been updated from the previous Letter of Intent [K. Abe et al., arXiv:1109.3262 [hep-ex]], based on the experience gained from the ongoing T2K experiment. With a total exposure of 7.5 MW $\times$ 10$^7$ sec integrated proton beam power (corresponding to $1.56\times10^{22}$ protons on target with a 30 GeV proton beam) to a $2.5$-degree off-axis neutrino beam produced by the J-PARC proton synchrotron, it is expected that the $CP$ phase $\delta_{CP}$ can be determined to better than 19 degrees for all possible values of $\delta_{CP}$, and $CP$ violation can be established with a statistical significance of more than $3\,\sigma$ ($5\,\sigma$) for $76$ ($58$) of the $\delta_{CP}$ parameter space

Hollow Sodium Tungsten Bronze (Na0.15WO3) Nanospheres: Preparation, Characterization, and Their Adsorption Properties

We report herein a facile method for the preparation of sodium tungsten bronzes hollow nanospheres using hydrogen gas bubbles as reactant for chemical reduction of tungstate to tungsten and as template for the formation of hollow nanospheres at the same time. The chemical composition and the crystalline state of the as-prepared hollow Na0.15WO3nanospheres were characterized complementarily, and the hollow structure formation mechanism was proposed. The hollow Na0.15WO3nanospheres showed large Brunauer–Emment–Teller specific area (33.8 m2 g−1), strong resistance to acids, and excellent ability to remove organic molecules such as dye and proteins from aqueous solutions. These illustrate that the hollow nanospheres of Na0.15WO3should be a useful adsorbent

Fifteen-Year Population Attributable Fractions and Causal Pies of Risk Factors for Newly Developed Hepatocellular Carcinomas in 11,801 Men in Taiwan

Development of hepatocellular carcinoma (HCC) is a multi-factorial process. Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are important risk factors of HCC. Host factors, such as alcohol drinking, may also play a role. This study aims to provide a synthesis view on the development of HCC by examining multiple risk factors jointly and collectively. Causal-pie modeling technique was applied to analyze a cohort of 11,801 male residents (followed up for 15 years) in Taiwan, during which a total of 298 incident HCC cases were ascertained. The rate ratios adjusted by age were further modeled by an additive Poisson regression. Population attributable fractions (PAFs) and causal-pie weights (CPWs) were calculated. A PAF indicates the magnitude of case-load reduction under a particular intervention scenario, whereas a CPW for a particular class of causal pies represents the proportion of HCC cases attributable to that class. Using PAF we observed a chance to reduce around 60% HCC risk moving from no HBV-related intervention to the total elimination of the virus. An additional ∼15% (or ∼5%) reduction can be expected, if the HBV-related intervention is coupled with an HCV-related intervention (or an anti-drinking campaign). Eight classes of causal pies were found to be significant, including four dose-response classes of HBV (total CPW=52.7%), one independent-effect class of HCV (CPW=14.4%), one HBV-alcohol interaction class (CPW=4.2%), one HBV-HCV interaction class (CPW=1.7%), and one all-unknown class (CPW=27.0%). Causal-pie modeling for HCC helps clarify the relative importance of each viral and host factor, as well as their interactions