Development of a Remotely Operated NDE System for Inspection of Hanford's Double Shell Waste Tank Knuckle Regions

This report documents work performed at the PNNL in FY01 to support development of a Remotely Operated NDE (RONDE) system capable of inspecting the knuckle region of Hanford's DSTs. The development effort utilized commercial off-the-shelf (COTS) technology wherever possible and provided a transport and scanning device for implementing the SAFT and T-SAFT techniques

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Background: Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods: In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings: The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p<0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p<0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation: In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding: Novo Nordisk, Denmark

Evaluation of SAFT/T-SAFT Technology for the Inspection of Hanford's Double Shell Waste Tank Knuckle Regions

Results of the examinations conducted at Pacific Northwest National Laboratory provided a firm engineering basis for establishing the proof-of-principle effectiveness for utilizing a combination of pulse-echo Synthetic Aperture Focusing Technique (SAFT) and tandem-SAFT (T-SAFT) inspection methodologies as applied to the problem of flaw detection, localization, and sizing in Hanford's double shell waste tank knuckle region and beyond

IGF-1 Controls GLUT3 Expression in Muscle via the Transcriptional Factor Sp1

Glucose transporter 3 (GLUT3), while first found in human fetal muscle, is predominantly expressed in brain and neural tissue. By several independent techniques we have previously shown that GLUT3 is expressed in human skeletal muscle cells. The structure of the human GLUT3 gene has not been previously reported nor has there been any evaluation of the 5′-untranslated region (UTR). To this end, we have cloned and sequenced the human GLUT3 gene. Insulin-like growth factor-1 (IGF-1) increased endogenous Glut3 protein in cultured L6 myotubes, and similarly stimulated luciferase activity in a construct of the human GLUT3 5′-UTR linked to a luciferase reporter gene. Actinomycin D, an inhibitor of mRNA synthesis, prevented IGF-1 stimulation of Glut3 protein. Transfection of L6 cells with Sp1 increased Glut3 and augmented IGF-1 stimulation of Glut3 expression. Knockdown of Glut3 expression in cultured L6 muscle cells using small interference RNA (siRNA) specific for Glut3 significantly reduced myocyte glucose uptake. DNAse footprinting and gel shift assays showed Sp1 specifically bound to the human GLUT3 5′-UTR. Substitution mutants of the human GLUT3 5′-UTR luciferase construct indicated that only one of three Sp1 site clusters was involved in IGF-1 action. These data, using both a human GLUT3 5′-UTR construct and L6 cells\u27 endogenous promoter, suggest that IGF-1 plays a role in maintaining muscle GLUT3 expression and basal glucose uptake via the transcriptional factor Sp1

Development of a Remotely Operated NDE System for Inspection of Hanford's Double Shell Waste Tank Knuckle Regions

This report documents work performed at the PNNL in FY01 to support development of a Remotely Operated NDE (RONDE) system capable of inspecting the knuckle region of Hanford's DSTs. The development effort utilized commercial off-the-shelf (COTS) technology wherever possible and provided a transport and scanning device for implementing the SAFT and T-SAFT techniques

Role of Retrograde Trafficking in Stress Response, Host Cell Interactions, and Virulence of Candida albicans

In Saccharomyces cerevisiae, the vacuolar protein sorting complexes Vps51/52/53/54 and Vps15/30/34/38 are essential for efficient endosome-to-Golgi complex retrograde transport. Here we investigated the function of Vps15 and Vps51, representative members of these complexes, in the stress resistance, host cell interactions, and virulence of Candida albicans. We found that C. albicans vps15Δ/Δ and vps51Δ/Δ mutants had abnormal vacuolar morphology, impaired retrograde protein trafficking, and dramatically increased susceptibility to a variety of stressors. These mutants also had reduced capacity to invade and damage oral epithelial cells in vitro and attenuated virulence in the mouse model of oropharyngeal candidiasis. Proteomic analysis of the cell wall of the vps51Δ/Δ mutant revealed increased levels of the Crh11 and Utr2 transglycosylases, which are targets of the calcineurin signaling pathway. The transcript levels of the calcineurin pathway members CHR11, UTR2, CRZ1, CNA1, and CNA2 were elevated in the vps15Δ/Δ and vps51Δ/Δ mutants. Furthermore, these strains were highly sensitive to the calcineurin-specific inhibitor FK506. Also, deletion of CHR11 and UTR2 further increased the stress susceptibility of these mutants. In contrast, overexpression of CRH11 and UTR2 partially rescued their defects in stress resistance, but not host cell interactions. Therefore, intact retrograde trafficking in C. albicans is essential for stress resistance, host cell interactions, and virulence. Aberrant retrograde trafficking stimulates the calcineurin signaling pathway, leading to the increased expression of Chr11 and Utr2, which enables C. albicans to withstand environmental stress

Femtosecond x-ray diffraction reveals a liquid–liquid phase transition in phase-change materials

In phase-change memory devices, a material is cycled between glassy and crystalline states. The highly temperature-dependent kinetics of its crystallization process enables application in memory technology, but the transition has not been resolved on an atomic scale. Using femtosecond x-ray diffraction and ab initio computer simulations, we determined the time-dependent pair-correlation function of phase-change materials throughout the melt-quenching and crystallization process. We found a liquid–liquid phase transition in the phase-change materials Ag4In3Sb67Te26 and Ge15Sb85 at 660 and 610 kelvin, respectively. The transition is predominantly caused by the onset of Peierls distortions, the amplitude of which correlates with an increase of the apparent activation energy of diffusivity. This reveals a relationship between atomic structure and kinetics, enabling a systematic optimization of the memory-switching kinetics

African American Church Participation and Health Care Practices

BACKGROUND: While religious involvement is associated with improvements in health, little is known about the relationship between church participation and health care practices. OBJECTIVES: To determine 1) the prevalence of church participation; 2) whether church participation influences positive health care practices; and 3) whether gender, age, insurance status, and levels of comorbidity modified these relationships. DESIGN: A cross-sectional analysis using survey data from 2196 residents of a low-income, African-American neighborhood. MEASUREMENTS: Our independent variable measured the frequency of church attendance. Dependent variables were: 1) Pap smear; 2) mammogram; and 3) dental visit—all taking place within 2 years; 4) blood pressure measurement within 1 year, 5) having a regular source of care, and 6) no perceived delays in care in the previous year. We controlled for socioeconomic factors and the number of comorbid conditions and also tested for interactions. RESULTS: Thirty-seven percent of community members went to church at least monthly. Church attendance was associated with increased likelihood of positive health care practices by 20% to 80%. In multivariate analyses, church attendance was related to dental visits (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.3 to 1.9) and blood pressure measurements (OR, 1.6; 95% CI, 1.2 to 2.1). Insurance status and number of comorbid conditions modified the relationship between church attendance and Pap smear, with increased practices noted for the uninsured (OR, 2.3; 95% CI, 1.2 to 4.1) and for women with 2 or more comorbid conditions (OR, 1.9; 95% CI, 1.1 to 3.5). CONCLUSION: Church attendance is an important correlate of positive health care practices, especially for the most vulnerable subgroups, the uninsured and chronically ill. Community- and faith-based organizations present additional opportunities to improve the health of low-income and minority populations