1,841 research outputs found

    Претензионная работа по топливу для предприятий энергетики

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    Background and aims: CREB (cAMP response element binding protein) transcription factors are key regulators of homeostatic functions in the liver, and CRE binding is increased in hepatic inflammation. During chronic hepatitis B virus (HBV) infection, mutations or deletions in the pre-S region are frequently observed. These mutations can affect the pre-S2/S promoter controlling HBV envelope protein expression (hepatitis B surface antigen (HBsAg)) and have been associated with worsened clinical outcome. We aimed to test if CREB activation impacts on HBsAg expression. Methods: The effect of the CREB inducer protein kinase A (PKA) was tested by coexpression with HBV wild-type vector in vitro. Luciferase reporter gene constructs were cloned to identify novel regulatory regions for the HBV pre-S2/S promoter. Electrophoretic mobility shift assay (EMSA) gelshift and supershift experiments were conducted to confirm DNA transcription factor binding. Results: Coexpression of HBV and PKA resulted in HBV-S mRNA induction and enhanced small envelope protein expression. We identified a CREB binding motif in the transcribed part of the pre-S2 region, contributing to basal S promoter activity via binding of activating transcription factor 2 (ATF2). A second CREB motif closely linked to the S-ATG showed a similar binding pattern involving ATF2 and CREB1, without appearing essential for basal promoter activity. Moreover, a sequence in the pre-S2 region is responsible for further transcriptional induction via CREB activators such as PKA and forskolin. EMSA experiments indicate that CREB1 and ATF4 are involved in complex formation conferring PKA dependent promoter activation. Conclusions: Our data suggest a novel mechanism by which HBV may utilise CREB/PKA signal transduction pathways of hepatocytes to enhance its HBsAg expression during homeostasis and hepatic inflammation

    Patient and allograft survival of Indo Asian and East Asian dialysis patients treated in Canada

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    Kidney failure is relatively common among Canadians of Asian origin. However, little is known about the health outcomes after initiation of renal replacement therapy in this population. Our study evaluates differences in the likelihood of renal transplantation and graft loss among Asian and white patients. We studied 21 523 adults of East Asian, Indo Asian or white ethnicity who had initiated dialysis in Canada from 1990–2000. Subjects were followed until death, loss to follow-up or end of study (2004). The proportion of the eligible subjects who were East Asian, Indo Asian, or white was 6, 3, and 91%, respectively. Compared to white patients, East Asian and Indo Asian patients were significantly less likely to receive a renal transplant after adjusting for potential confounding factors. This disparity is greater for transplants from living donors as compared to those from deceased donors. The adjusted death censored graft loss in transplant recipients was not significantly different between ethnic groups. The adjusted risk of death following transplantation, however, was significantly lower in Indo Asian than in white patients. Our findings show that in a Canadian population, patients of East Asian or Indo Asian origin had lower rates of renal transplantation than white patients, especially for living donor transplantation. These findings warrant further study, especially given the good graft outcomes in these individuals

    Optogenetic Stimulation of the Basolateral Amygdala Increased Theta-Modulated Gamma Oscillations in the Hippocampus

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    The amygdala can modulate declarative memory. For example, previous research in rats and humans showed that brief electrical stimulation to the basolateral complex of the amygdala (BLA) prioritized specific objects to be consolidated into long term memory in the absence of emotional stimuli and without awareness of stimulation. The capacity of the BLA to influence memory depends on its substantial projections to many other brain regions, including the hippocampus. Nevertheless, how activation of the BLA influences ongoing neuronal activity in other regions is poorly understood. The current study used optogenetic stimulation of putative glutamatergic neurons in the BLA of freely exploring rats to determine whether brief activation of the BLA could increase in the hippocampus gamma oscillations for which the amplitude was modulated by the phase of theta oscillations, an oscillatory state previously reported to correlate with good memory. BLA neurons were stimulated in 1-s bouts with pulse frequencies that included the theta range (8 Hz), the gamma range (50 Hz), or a combination of both ranges (eight 50-Hz bursts). Local field potentials were recorded in the BLA and in the pyramidal layer of CA1 in the intermediate hippocampus. A key question was whether BLA stimulation at either theta or gamma frequencies could combine with ongoing hippocampal oscillations to result in theta-modulated gamma or whether BLA stimulation that included both theta and gamma frequencies would be necessary to increase theta–gamma comodulation in the hippocampus. All stimulation conditions elicited robust responses in BLA and CA1, but theta-modulated gamma oscillations increased in CA1 only when BLA stimulation included both theta and gamma frequencies. Longer bouts (5-s) of BLA stimulation resulted in hippocampal activity that evolved away from the initial oscillatory states and toward those characterized more by prominent low-frequency oscillations. The current results indicated that one mechanism by which the amygdala might influence declarative memory is by eliciting neuronal oscillatory states in the hippocampus that benefit memory

    Prediction of residual stresses in girth welded pipes using an artificial neural network approach

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    Management of operating nuclear power plants greatly relies on structural integrity assessments for safety critical pressure vessels and piping components. In the present work, residual stress profiles of girth welded austenitic stainless steel pipes are characterised using an artificial neural network approach. The network has been trained using residual stress data acquired from experimental measurements found in literature. The neural network predictions are validated using experimental measurements undertaken using neutron diffraction and the contour method. The approach can be used to predict through-wall distribution of residual stresses over a wide range of pipe geometries and welding parameters thereby finding potential applications in structural integrity assessment of austenitic stainless steel girth welds

    Identifying factors associated with sedentary time after stroke. Secondary analysis of pooled data from nine primary studies.

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    <p><b>Background</b>: High levels of sedentary time increases the risk of cardiovascular disease, including recurrent stroke.</p> <p><b>Objective</b>: This study aimed to identify factors associated with high sedentary time in community-dwelling people with stroke.</p> <p><b>Methods</b>: For this data pooling study, authors of published and ongoing trials that collected sedentary time data, using the activPAL monitor, in community-dwelling people with stroke were invited to contribute their raw data. The data was reprocessed, algorithms were created to identify sleep-wake time and determine the percentage of waking hours spent sedentary. We explored demographic and stroke-related factors associated with total sedentary time and time in uninterrupted sedentary bouts using unique, both univariable and multivariable, regression analyses.</p> <p><b>Results</b>: The 274 included participants were from Australia, Canada, and the United Kingdom, and spent, on average, 69% (SD 12.4) of their waking hours sedentary. Of the demographic and stroke-related factors, slower walking speeds were significantly and independently associated with a higher percentage of waking hours spent sedentary (p = 0.001) and uninterrupted sedentary bouts of <i>>30</i> and <i>>60 min</i> (p = 0.001 and p = 0.004, respectively). Regression models explained 11–19% of the variance in total sedentary time and time in prolonged sedentary bouts.</p> <p><b>Conclusion</b>: We found that variability in sedentary time of people with stroke was largely unaccounted for by demographic and stroke-related variables. Behavioral and environmental factors are likely to play an important role in sedentary behavior after stroke. Further work is required to develop and test effective interventions to address sedentary behavior after stroke.</p
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