1,881 research outputs found

    Load cell protection device Patent

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    Load cell protection device using spring-loaded breakaway mechanis

    The Senate’s torture report shows how hamstrung Congressional oversight of the intelligence community really is

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    On December 9th, the U.S. Senate Select Committee on Intelligence released the executive summary of its longer report into the Central Intelligence Agency’s (CIA) use of ‘enhanced interrogation methods’ after 9/11. Jennifer Kibbe writes that the report is replete with examples of the CIA’s inaccurate representations concerning its programs, and its lack of cooperation with the committee’s investigation. She argues that the report illustrates the difficulties that Congress faces in holding highly secretive agencies such as the CIA to account

    Adenovirus-mediated gene transfer to liver grafts: An improved method to maximize infectivity

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    Background. Adenoviral gene therapy in liver transplantation has many potential applications, but current vector delivery methods to grafts lack efficiency and require high titers. In this study, we attempted to improve gene delivery efficacy using three different delivery methods to liver grafts with adenoviral vector encoding the LacZ marker gene (AdLacZ). Methods. AdLacZ was delivered to cold preserved rat liver grafts by: (1) continuous perfusion via the portal vein (portal perfusion), (2) continuous perfusion via both the portal vein and hepatic artery (dual perfusion), and (3) trapping viral perfusate in the liver vasculature by clamping outflow (clamp technique). Results. Using 1x109 plaque-forming units of Ad-LacZ (multiplicity of infection of 0.4), transduction rate in 3-hr preserved liver grafts, determined by 5-bromo-4-chromo-3-indolyl-β-D-galactopyranoside staining and β-galactosidase assay 48 hr after transplantation, was best with clamp technique (21.5±2.7% 5-bromo-4-chromo-3-indolyl-β-D- galactopyranoside-positive cells and 81.1±3.6 U/g β-galactosidase), followed by dual perfusion (18.5±1.8%, 66.6±19.4 U/g) and portal perfusion (8.8±2.5%, 19.7±15.4 U/g). Further studies using clamp technique demonstrated a near-maximal gene transfer rate of 30% at multiplicity of infection of 0.4 with prolonged cold ischemia to 18 hr. Transgene expression was stable for 2 weeks and slowly declined to 7.8±12.1% at day 28. Lack of inflammatory response was confirmed by histopathological examination and liver enzymes. Transduction was selectively induced in hepatocytes with nearly no extrahepatic transgene expression in the lung and spleen. Conclusions. The clamp technique provides a highly efficient viral gene delivery method to cold preserved liver grafts. This method offers maximal infectivity of adenoviral vector with minimal technical manipulation

    Intra-islet GLP-1, but not CCK, is necessary for β-cell function in mouse and human islets

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    Glucagon-like peptide 1 (GLP-1) and cholecystokinin (CCK) are gut-derived peptide hormones known to play important roles in the regulation of gastrointestinal motility and secretion, appetite, and food intake. We have previously demonstrated that both GLP-1 and CCK are produced in the endocrine pancreas of obese mice. Interestingly, while GLP-1 is well known to stimulate insulin secretion by the pancreatic β-cells, direct evidence of CCK promoting insulin release in human islets remains to be determined. Here, we tested whether islet-derived GLP-1 or CCK is necessary for the full stimulation of insulin secretion. We confirm that mouse pancreatic islets secrete GLP-1 and CCK, but only GLP-1 acts locally within the islet to promote insulin release ex vivo. GLP-1 is exclusively produced in approximately 50% of α-cells in lean mouse islets and 70% of α-cells in human islets, suggesting a paracrine α to β-cell signaling through the β-cell GLP-1 receptor. Additionally, we provide evidence that islet CCK expression is regulated by glucose, but its receptor signaling is not required during glucose-stimulated insulin secretion (GSIS). We also see no increase in GSIS in response to CCK peptides. Importantly, all these findings were confirmed in islets from non-diabetic human donors. In summary, our data suggest no direct role for CCK in stimulating insulin secretion and highlight the critical role of intra-islet GLP-1 signaling in the regulation of human β-cell function

    Association of 6-Minute Walk Performance and Physical Activity With Incident Ischemic Heart Disease Events and Stroke in Peripheral Artery Disease.

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    BackgroundWe determined whether poorer 6-minute walk performance and lower physical activity levels are associated with higher rates of ischemic heart disease (IHD) events in people with lower extremity peripheral artery disease (PAD).Methods and resultsFive hundred ten PAD participants were identified from Chicago-area medical centers and followed prospectively for 19.0±9.5 months. At baseline, participants completed the 6-minute walk and reported number of blocks walked during the past week (physical activity). IHD events were systematically adjudicated and consisted of new myocardial infarction, unstable angina, and cardiac death. For 6-minute walk, IHD event rates were 25/170 (14.7%) for the third (poorest) tertile, 10/171 (5.8%%) for the second tertile, and 6/169 (3.5%) for the first (best) tertile (P=0.003). For physical activity, IHD event rates were 21/154 (13.6%) for the third (poorest) tertile, 15/174 (8.6%) for the second tertile, and 5/182 (2.7%) for the first (best) tertile (P=0.001). Adjusting for age, sex, race, smoking, body mass index, comorbidities, and physical activity, participants in the poorest 6-minute walk tertile had a 3.28-fold (95% CI 1.17 to 9.17, P=0.024) higher hazard for IHD events, compared with those in the best tertile. Adjusting for confounders including 6-minute walk, participants in the poorest physical activity tertile had a 3.72-fold (95% CI 1.24 to 11.19, P=0.019) higher hazard for IHD events, compared with the highest tertile.ConclusionsSix-minute walk and physical activity predict IHD event rates in PAD. Further study is needed to determine whether interventions that improve 6-minute walk, physical activity, or both can reduce IHD events in PAD
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