981 research outputs found
Reduced glycogen availability is associated with increased AMPKα2 activity, nuclear AMPKα2 protein abundance, and GLUT4 mRNA expression in contracting human skeletal muscle
Glycogen availability can influence glucose transporter 4 (GLUT4) expression in skeletal muscle through unknown mechanisms. The multisubstrate enzyme AMP-activated protein kinase (AMPK) has also been shown to play an important role in the regulation of GLUT4 expression in skeletal muscle. During contraction, AMPK [alpha]2 translocates to the nucleus and the activity of this AMPK isoform is enhanced when skeletal muscle glycogen is low. In this study, we investigated if decreased pre-exercise muscle glycogen levels and increased AMPK [alpha]2 activity reduced the association of AMPK with glycogen and increased AMPK [alpha]2 translocation to the nucleus and GLUT4 mRNA expression following exercise. Seven males performed 60 min of exercise at ~70% [VO.sub.2] peak on 2 occasions: either with normal (control) or low (LG) carbohydrate pre-exercise muscle glycogen content. Muscle samples were obtained by needle biopsy before and after exercise. Low muscle glycogen was associated with elevated AMPK [alpha]2 activity and acetyl-CoA carboxylase [beta] phosphorylation, increased translocation of AMPK [alpha]2 to the nucleus, and increased GLUT4 mRNA. Transfection of primary human myotubes with a constitutively active AMPK adenovirus also stimulated GLUT4 mRNA, providing direct evidence of a role of AMPK in regulating GLUT4 expression. We suggest that increased activation of AMPK [alpha]2 under conditions of low muscle glycogen enhances AMPK [alpha]2 nuclear translocation and increases GLUT4 mRNA expression in response to exercise in human skeletal muscle. <br /
Heliostat-field soiling predictions and cleaning resource optimization for solar tower plants
This paper presents a novel methodology for characterizing soiling losses
through experimental measurements. Soiling predictions were obtained by
calibrating a soiling model based on field measurements from a 50 MW modular
solar tower project in Mount Isa, Australia. The study found that the mean
predicted soiling rate for horizontally fixed mirrors was 0.12 percentage
points per day (pp/d) during low dust seasons and 0.22 pp/d during high
seasons. Autoregressive time series models were employed to extend two years of
onsite meteorological measurements to a 10-year period, enabling the prediction
of heliostat-field soiling rates. A fixed-frequency cleaning heuristic was
applied to optimise the cleaning resources for various operational policies by
balancing direct cleaning resource costs against the expected lost production,
which was computed by averaging multiple simulated soiling loss trajectories.
Analysis of resource usage showed that the cost of fuel and operator salaries
contributed 42 % and 35 % respectively towards the cleaning cost. In addition,
stowing heliostats in the horizontal position at night increased daily soiling
rates by 114 % and the total cleaning costs by 51 % relative to vertically
stowed heliostat-field. Under a simplified night-time-only power production
configuration, the oversized solar field effectively charged the thermal
storage during the day, despite reduced mirror reflectance due to soiling.
These findings suggest that the plant can maintain efficient operation even
with a reduced cleaning rate. Finally, it was observed that performing cleaning
operations during the day led to a 7 % increase in the total cleaning cost
compared to a night-time cleaning policy. This was primarily attributed to the
need to park operational heliostats for cleaning
High intensity interval training improves liver and adipose tissue insulin sensitivity
Objective: Endurance exercise training reduces insulin resistance, adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD), an effect often associated with modest weight loss. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose in individuals with type 2 diabetes independently of weight loss; however, the organs affected and mechanisms mediating the glucose lowering effects are not known. Intense exercise increases phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) by AMP-activated protein kinase (AMPK) in muscle, adipose tissue and liver. AMPK and ACC are key enzymes regulating fatty acid metabolism, liver fat content, adipose tissue inflammation and insulin sensitivity but the importance of this pathway in regulating insulin sensitivity with HIIT is unknown. Methods: In the current study, the effects of 6 weeks of HIIT were examined using obese mice with serineâalanine knock-in mutations on the AMPK phosphorylation sites of ACC1 and ACC2 (AccDKI) or wild-type (WT) controls. Results: HIIT lowered blood glucose and increased exercise capacity, food intake, basal activity levels, carbohydrate oxidation and liver and adipose tissue insulin sensitivity in HFD-fed WT and AccDKI mice. These changes occurred independently of weight loss or reductions in adiposity, inflammation and liver lipid content. Conclusions: These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC
Atrial fibrillation after minimally invasive direct coronary artery bypass surgery
AbstractOBJECTIVESThe study compared the adjusted risk for developing atrial fibrillation (AF) after minimally invasive direct coronary artery bypass surgery (MIDCAB) and coronary artery bypass graft surgery (CABG).BACKGROUNDAtrial fibrillation results in increased morbidity and delays hospital discharge after CABG. Recently, MIDCAB has been explored as an alternative to CABG. Because of differences in surgical approach between the two procedures, the incidence of AF may differ.METHODSRandomly selected patients undergoing CABG and MIDCAB were examined. Baseline variables and postoperative course were recorded through review of medical record data.RESULTSThe MIDCAB patients were younger than CABG patients (64 ± 12 vs. 67 ± 10, p < 0.04) and had less extensive coronary artery disease (53% of MIDCAB vs. 3% of CABG had single-vessel disease, while 15% of MIDCAB vs. 69% of CABG had triple-vessel disease, p < 0.001 for overall group comparisons). No other differences in clinical or treatment data were noted. Postoperative AF occurred less often after MIDCAB (23% vs 39%, p = 0.02). Other significant factors associated with postoperative AF included age (p = 0.0024), prior AF (p = 0.0007), left main disease (p = 0.01), number of vessels bypassed (p = 0.009), absence of postoperative beta-blocker therapy (p = 0.0001), and a serious postoperative complication (p = 0.0018). Because of differences between CABG and MIDCAB patients, multivariate logistic analysis was performed to determine independent predictors of postoperative AF. The type of surgery (CABG vs. MIDCAB) was no longer a significant predictor of postoperative AF (estimated relative risk for AF in CABG vs. MIDCAB patients: 1.57, 95% confidence interval (0.82â2.52).CONCLUSIONSAlthough AF appears to be less common after MIDCAB than after CABG, the lower incidence is due to different clinical characteristics of patients undergoing these procedures
Skeletal muscle AMPK is essential for the maintenance of FNDC5 expression
Fibronectin type III domainâcontaining protein 5 (FNDC5) expression is controlled by the transcriptional coâactivator, peroxisome proliferatorâactivated receptor gamma, coactivator 1 alpha (PGC1α). FNDC5 expression has been shown to be increased in muscle in response to endurance exercise in some but not all studies, therefore a greater understanding of the mechanisms controlling this process are needed. The AMPâactivated protein kinase (AMPK) is activated by exercise in an intensity dependent manner and is an important regulator of PGC1α activity; therefore, we explored the role of AMPK in the regulation of FNDC5 using AMPK ÎČ1ÎČ2 double muscleânull mice (AMPK DMKO), which lack skeletal muscle AMPK activity. We found that FNDC5 expression is dramatically reduced in resting muscles of AMPK DMKO mice compared to wildâtype littermates. In wildâtype mice, activating phosphorylation of AMPK was elevated immediately post contraction and was abolished in muscle from AMPK DMKO mice. In contrast, PGC1α was increased in both wildâtype and AMPK DMKO mice 3 h post contraction but FNDC5 protein expression was not altered. Lastly, acute or chronic activation of AMPK with the pharmacological AMPK activator AICAR did not increase PGC1α or FNDC5 expression in muscle. These data indicate that skeletal muscle AMPK is required for the maintenance of basal FNDC5 expression
A phase 2, multicenter, openâlabel study of sepantronium bromide (YM155) plus docetaxel in patients with stage III (unresectable) or stage IV melanoma
Survivin is a microtubuleâassociated protein believed to be involved in preserving cell viability and regulating tumor cell mitosis, and it is overexpressed in many primary tumor types, including melanoma. YM155 is a firstâinâclass survivin suppressant. The purpose of this Phase 2 study was to evaluate the 6âmonth progressionâfree survival (PFS) rate in patients with unresectable Stage III or IV melanoma receiving a combination of YM155 plus docetaxel. The study had two parts: Part 1 established the dose of docetaxel that was tolerable in combination with YM155, and Part 2 evaluated the tolerable docetaxel dose (75 mg/m2) in combination with YM155 (5 mg/m2 per day continuous infusion over 168 h every 3 weeks). The primary endpoint was 6âmonth PFS rate. Secondary endpoints were objective response rate (ORR), 1âyear overall survival (OS) rate, time from first response to progression, clinical benefit rate (CBR), and safety. Sixtyâfour patients with metastatic melanoma were treated with docetaxel and YM155. Eight patients received an initial docetaxel dose of 100 mg/m2 and 56 patients received 75 mg/m2 of docetaxel. Sixâmonth PFS rate per Independent Review Committee (IRC) was 34.8% (n = 64; 95% CI, 21.3â48.6%), and per Investigator was 31.3% (n = 64; 95% CI, 19.5â43.9%). The best ORR (complete response [CR] + partial response [PR]) per IRC was 12.5% (8/64). The stable disease (SD) rate was 51.6% (33/64), leading to a CBR (CR + PR + SD) of 64.1% (41/64). Estimated probability of 1âyear survival was 56.3%. YM155 is a novel agent showing modest activity when combined with docetaxel for treating patients with melanoma. YM155 was generally well tolerated, but the predetermined primary efficacy endpoint (i.e., 6âmonth PFS rate â„20%) was not achieved.YM155 is a firstâinâclass agent that suppresses surviving. Though YM155 combined with docetaxel was generally wellâtolerated in this study, it showed limited efficacy in the treatment of metastatic melanoma.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111757/1/cam4363.pd
Comparison Of The Genesis Solar Wind Regime Algorithm Results With Solar Wind Composition Observed By ACE
Launched on 8 August 2001, the NASA Genesis mission is now collecting samples of the solar wind in various materials, and will return those samples to Earth in 2004 for analysis. A primary science goal of Genesis is the determination of the isotopic and elemental composition of the solar atmosphere from the solar wind material returned. In particular, Genesis will provide measurements of those species that are not provided by solar and in situ observations. We know from in situ measurements that the solar wind exhibits compositional variations across different types of solar wind flows. Therefore, Genesis exposes different collectors to solar wind originating from three flow types: coronal hole, coronal mass ejection (CME), and interstream flows. Flow types are identified using in situ measurements of solar wind protons, alphas, and electrons from electrostatic analyzers carried by Genesis. The flow regime selection algorithm and subsequent collector deployment on Genesis act autonomously. We present an assessment of composition variations of O, He, and Mg ions observed by ACE/SWICS concurrent with Genesis observations, and compare these to the Genesis algorithm decisions. Not only does this serve as a test of the algorithm, the compilation of composition vs. regime will be important for comparison to the abundances determined from sample analysis at the end of the mission. © 2003 American Institute of PhysicsPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87657/2/632_1.pd
Blood spots as an alternative to whole blood collection and the effect of a small monetary incentive to increase participation in genetic association studies
<p>Abstract</p> <p>Background</p> <p>Collection of buccal cells from saliva for DNA extraction offers a less invasive and convenient alternative to venipuncture blood collection that may increase participation in genetic epidemiologic studies. However, dried blood spot collection, which is also a convenient method, offers a means of collecting peripheral blood samples from which analytes in addition to DNA can be obtained.</p> <p>Methods</p> <p>To determine if offering blood spot collection would increase participation in genetic epidemiologic studies, we conducted a study of collecting dried blood spot cards by mail from a sample of female cancer cases (n = 134) and controls (n = 256) who were previously selected for a breast cancer genetics study and declined to provide a venipuncture blood sample. Participants were also randomized to receive either a 2.00 incentive vs. 26% for no incentive, p = 0.6), it was significantly associated with participation among the breast cancer cases (48% vs. 27%, respectively, p = 0.01). There did not appear to be any bias in response since no differences between cases and controls and incentive groups were observed when examining several demographic, work history and radiation exposure variables.</p> <p>Conclusion</p> <p>This study demonstrates that collection of dried blood spot cards in addition to venipuncture blood samples may be a feasible method to increase participation in genetic case-control studies.</p
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