Miracle-dz/UniFAR-FTUs huggingface dataset:
The effects of amino acids on glucose metabolism of isolated rat skeletal muscle are independent of insulin and the mTOR / S 6 K pathway

Stadlbauer K, Brunmair B, Szöcs Z, Krebs M, Luger A, Fürnsinn C. The effects of amino acids on glucose metabolism of isolated rat skeletal muscle are independent of insulin and the mTOR/S6K pathway. Am J Physiol Endocrinol Metab 297: E785–E792, 2009. First published July 21, 2009; doi:10.1152/ajpendo.00061. 2009. —Two mechanisms have been proposed for the modulation of skeletal muscle glucose metabolism by amino acids. Whereas studies on humans and cultured cells suggested acute insulin desensitization via mammalian target of rapamycin (mTOR) and its downstream target p70 S6 kinase (S6K), investigations using native specimens of rat muscle hinted at impairment of glucose oxidation by competition for mitochondrial oxidation. To better understand these seemingly contradictory findings, we explored the effects of high concentrations of mixed amino acids on fuel metabolism and S6K activity in freshly isolated specimens of rat skeletal muscle. In this setting, increasing concentrations of amino acids dose-dependently reduced the insulin-stimulated rates of CO2 production from glucose and palmitate (decrease in glucose oxidation induced by addition of 5.5, 11, 22, and 44 mmol/l amino acids: 16 3, 25 7, 44 4, 62 4%; P 0.02 each). This effect could not be attributed to insulin desensitization, because it was not accompanied by any reduction of insulin-stimulated glucose transport [ 12 16, 17 22, 21 33, 13 12%; all nonsignificant (NS)] or glycogen synthesis ( 1 6, 5 6, 9 8, 6 5%; all NS) and because it persisted without insulin stimulation. Abrogation of S6K activity by the mTOR blocker rapamycin failed to counteract amino acid-induced inhibition of glucose and palmitate oxidation, which therefore was obviously independent of mTOR/S6K signaling (decrease in glucose oxidation by addition of 44 mmol/l amino acids: without rapamycin, 60 4%; with rapamycin, 50 13%; NS). We conclude that amino acids can directly affect muscle glucose metabolism via two mechanisms, mTOR/S6K-mediated insulin desensitization and mitochondrial substrate competition, with the latter predominating in isolated rat muscle.
The 5 year effect of bypass surgery on relief of angina and exercise performance.

The 5 year effect of medical vs surgical treatment on symptoms and exercise performance was evaluated in patients with stable angina who entered the Veterans Administration Cooperative Study from 1972 to 1974. Severity of angina was evaluated by a physician-administered angina questionnaire and physical working capacity was assessed by exercise testing. Angina was substantially relieved in surgical patients at 1 year, with 78% having mild or no angina compared with only 28% at entry. The corresponding rates in medical patients showed little change: 38% at 1 year and 32% at entry. At 5 years the percentage of surgical patients with mild or absent angina decreased from the 1 year rate of 78% to 64%, whereas the medical group exhibited a small increase from 38% to 49%. Similar results were obtained by evaluating changes in angina compared to entry. At 1 year 49% of surgical patients were markedly improved compared with only 12% of medical patients. At 5 years the percentage of surgical patients who remained markedly improved decreased to 41%, whereas the medical group with marked improvement increased slightly from 12% at 1 year to 17% at 5 years. Medication requirements were markedly reduced in surgical patients with only a slight increase in medical patients. Exclusion of nonadherers from the analysis did not change the results. Exercise testing revealed comparable changes in physical performance. At 1 year surgical patients had fewer tests stopped by angina compared with medical patients (28% vs 64%), a higher estimated oxygen consumption (26 vs 21 ml/kg/min) and treadmill exercise duration (7.3 vs 4.9 min). Other measures of exercise performance were comparably improved. (ABSTRACT TRUNCATED AT 250 WORDS)
Mentoring Online Graduate Students: Partners in Scholarship

Mentoring graduate students toward scholarly research and writing activities has become an important area of focus for faculty at the Centre for Nursing and Health Studies at Athabasca University in Alberta, Canada. With an emphasis on teaching excellence, instructors seek out and create experiences to involve graduate students in their own programme of research and publication. However, despite a plethora of literature available on the concept of mentoring, few definitive guidelines exist to illustrate what the process might look like within Masters programmes offered exclusively through a WebCT online environment. This paper describes an approach to mentoring two graduate students in the Master of Health Studies programme that was perceived as positive and mutually beneficial for the prote´ge´s as well as the mentor. Insights are revealed into the experiences that these students found both engaging and difficult as they developed skills in analysing qualitative research and submitting manuscripts for publication. The students’ stories are discussed to describe significant features of the experience of ‘partnering in scholarship’ with their teacher. Suggestions and practical strategies for mentoring online graduate students are offered.
Down-regulation of BRCA 1-BARD 1 Ubiquitin Ligase by CDK 2

BRCA1, a breast and ovarian tumor suppressor, is a phosphoprotein whose cellular expression level is regulated in a cell cycle–dependent manner. BRCA1 interacts with BARD1 to generate significant ubiquitin ligase activity which catalyzes nontraditional Lys-6-linked polyubiquitin chains. However, it is not clear how the activity is regulated and how this affects BRCA1’s multiple cellular functions. Here we show that the ubiquitin ligase activity of BRCA1-BARD1 is down-regulated by CDK2. During the cell cycle, BARD1 expression can largely be categorized into three patterns: moderately expressed in a predominantly unphosphorylated form in early G1 phase, expressed at low levels in both phosphorylated and unphosphorylated forms during late G1 and S phases, and highly expressed in its phosphorylated form during mitosis coinciding with BRCA1 expression. CDK2-cyclin A1/E1 and CDK1cyclin B1 phosphorylate BARD1 on its NH2 terminus in vivo and in vitro . Intriguingly, the BRCA1-BARD1–mediated in vivo ubiquitination of nucleophosmin/B23 (NPM) and autoubiquitination of BRCA1 are dramatically disrupted by coexpression of CDK2-cyclin A1/E1, but not by CDK1-cyclin B1. The inhibition of ubiquitin ligase activity is not due to the direct effect of the kinases on BARD1 because an unphosphorylatable mutant of BARD1, S148A/S251A/S288A/T299A, is still inhibited by CDK2-cyclin E1. Alternatively, BRCA1 and BARD1 are likely exported to the cytoplasm and their expressions are remarkably reduced by CDK2-cyclin E1 coexpression. Recognizing the importance of cyclin E1 overexpression in breast cancer development, these results suggest a CDK2-BRCA1-NPM pathway that coordinately functions in cell growth and tumor progression pathways. (Cancer Res 2005; 65(1): 6-10)
Dependence of Voltage and Size on Write Error Rates in Spin-Transfer Torque Magnetic Random-Access Memory

The dependence of the write-error rate (WER) on the applied write voltage, write pulse width, and device size was examined in individual devices of a spin-transfer torque (STT) magnetic random-access memory (MRAM) 4 kbit chip. We present 10 ns switching data at the 10-6 error level for 655 devices, ranging in diameter from 50 nm to 11 nm, to make a statistically significant demonstration that a specific magnetic tunnel junction stack with perpendicular magnetic anisotropy is capable of delivering good write performance in junction diameters range from 50 to 11 nm. Furthermore, write-error-rate data on one 11 nm device down to an error rate of 7×10-10 was demonstrated at 10 ns with a write current of 7.5 μA, corresponding to a record low switching energy below 100 fJ.
Peritoneal dialysis in children under two years of age.

BACKGROUND Although results of peritoneal dialysis (PD) in small children have improved during recent years, the youngest children have poorer growth, more infections and higher mortality than do older children. METHODS In this retrospective study, we analysed patient records of all children under age 2 treated with continuous peritoneal dialysis (CPD) between 1995 and 2000 in Finland. Diagnoses leading to renal failure in these 23 children were congenital nephrotic syndrome of the Finnish type (13), polycystic kidney disease (4), a urethral valve (3), renal insufficiency due to neonatal asphyxia (2) and Prune-Belly syndrome (1). Of these 23, 17 (74%) were anuric. RESULTS The mean age at the onset of PD was 0.4 years and the mean time on dialysis 1.4 years. Hernias were diagnosed in 57%. The peritonitis rate was 1:14.5 patient-months, and 30% were peritonitis-free. Hypertension was common, and 70% had at least one period on antihypertensive medication. None of the patients had pulmonary oedema or dialysis-related seizures. The mean height standard deviation score (hSDS) at the start of PD (n = 16) was -2.0 and after 9 months -1.6. Catch-up growth was documented in 64% of the patients during dialysis. Hospitalization time was 124 days/patient-year. Two patients (9%) died. CONCLUSIONS Our results are reassuring. Mortality was low, laboratory parameters were acceptable and growth was good. Peritonitis rate was comparable to that in older children. Correction of inguinal hernia should be routinely performed; high blood pressure is still a problem.
Improved cycling time-trial performance after ingestion of a caffeine energy drink.

CONTEXT Not all athletic competitions lend themselves to supplementation during the actual event, underscoring the importance of preexercise supplementation to extend endurance and improve exercise performance. Energy drinks are composed of ingredients that have been found to increase endurance and improve physical performance. PURPOSE The purpose of the study was to investigate the effects of a commercially available energy drink, ingested before exercise, on endurance performance. METHODS The study was a double-blind, randomized, crossover design. After a 12-hr fast, 6 male and 6 female trained cyclists (mean age 27.3 +/- 1.7 yr, mass 68.9 +/- 3.2 kg, and VO2 54.9 +/- 2.3 ml x kg-1 x min-1) consumed 500 ml of either flavored placebo or Red Bull Energy Drink (ED; 2.0 g taurine, 1.2 g glucuronolactone, 160 mg caffeine, 54 g carbohydrate, 40 mg niacin, 10 mg pantothenic acid, 10 mg vitamin B6, and 10 microg vitamin B12) 40 min before a simulated cycling time trial. Performance was measured as time to complete a standardized amount of work equal to 1 hr of cycling at 70% Wmax. RESULTS Performance improved with ED compared with placebo (3,690 +/- 64 s vs. 3,874 +/- 93 s, p < .01), but there was no difference in rating of perceived exertion between treatments. b-Endorphin levels increased during exercise, with the increase for ED approaching significance over placebo (p = .10). Substrate utilization, as measured by open-circuit spirometry, did not differ between treatments. CONCLUSION These results demonstrate that consuming a commercially available ED before exercise can improve endurance performance and that this improvement might be in part the result of increased effort without a concomitant increase in perceived exertion.
Title Resource Planning in Disaster Response – Decision Support Models and Methodologies Subtitle None Abstract Managing the response to natural, man-made and technical disasters becomes increasingly important in the light of climate change, globalization, urbanization and growing conflicts. Sudden 

Managing the response to natural, man-made and technical disasters becomes increasingly important in the light of climate change, globalization, urbanization and growing conflicts. Sudden onset disasters are typically characterized by high stakes, time pressure and uncertain, conflicting or lacking information. Since the planning and management of response is a complex task, decision makers of aid organizations can thus benefit from decision support methods and tools. A key task is the joint allocation of rescue units and the scheduling of incidents under different conditions of collaboration. We present an approach to support decision makers, who coordinate response units, by (a) suggesting mathematical formulations of decision models, (b) providing heuristic solution procedures and (c) evaluating the heuristics against both current best practice behavior and optimal solutions. Our computational experiments show that, for the generated problem instances, (1) current best practice behavior can be improved substantially by our heuristics, (2) the gap between heuristic and optimal solutions is very low for instances without collaboration and (3) our heuristics are capable of providing solutions for all generated instances in less than a second on a state-of-the-art PC.
Slow-binding inhibition of Escherichia coli cystathionine beta-lyase by L-aminoethoxyvinylglycine: a kinetic and X-ray study.

The pyridoxal 5'-phosphate (PLP)-dependent cystathionine beta-lyase (CBL) was previously found to be inhibited by the natural toxins rhizobitoxine and l-aminoethoxyvinylglycine (AVG). The present study characterizes the interaction of Escherichia coli CBL with AVG and methoxyvinylglycine (MVG) by a combination of kinetic methods and X-ray crystallography. Upon AVG treatment, time-dependent, slow-binding inhibition [Morrison, J. F. (1982) Trends Biochem. Sci. 7, 102-105] was observed due to the generation of a long-lived, slowly dissociating enzyme-inhibitor complex. Kinetic analysis revealed a one-step inhibition mechanism (CBL + AVG --> CBLAVG, Ki = 1.1 +/- 0.3 microM) with an association rate constant (k1) of 336 +/- 40 M-1 s-1. This value is several orders of magnitude lower than typical bimolecular rate constants of ES formation, suggesting that additional steps occur before formation of the first detectable CBLAVG complex. Loss of activity is paralleled by the conversion of the pyridoxaldimine 426 nm chromophore to a 341 nm-absorbing species. On the basis of the recently solved structure of native CBL [Clausen, T. , et al. (1996) J. Mol. Biol. 262, 202-224], it was possible to elucidate the X-ray structure of the CBLAVG complex and to refine it to an R-factor of 16.4% at 2.2 A resolution. The refined structure reveals the geometry of the bound inhibitor and its interactions with residues in the active site of CBL. Both the X-ray structure and the absorbance spectrum of the CBLAVG complex are compatible with a ketimine as the reaction product. Thus, the inhibitor seems to bind in a similar way to CBL as the substrate, but after alpha-proton abstraction, the reaction proceeds in a CBL nontypical manner, i.e. protonation of PLP-C4', resulting in the "dead-end" ketimine PLP derivative. The CBLAVG structure furthermore suggests a binding mode for rhizobitoxine and explains the failure of MVG to inhibit CBL.
Influence of prior fasciotomy on infection after open reduction and internal fixation of tibial plateau fractures.

BACKGROUND High-energy tibial plateau fractures may present with an acute or impending compartment syndrome requiring emergent fasciotomy. There is little information regarding the optimal management of the fasciotomy wound with respect to the subsequent definitive internal fixation of the tibial plateau fracture. The purpose of this study was to compare the rate of infection complication after internal fixation of tibial plateau fractures in patients requiring fasciotomy for compartment syndrome with patients in whom a fasciotomy was not required. METHODS We retrospectively reviewed all tibial plateau fractures presenting over a 55-month period. Fourteen patients who presented with an associated compartment syndrome requiring fasciotomy and 128 patients in whom a fasciotomy was not performed met inclusion criteria. Patients age, sex, mechanism of injury, management of their fasciotomy, operative treatment of their plateau fracture, follow-up surgical procedures, follow-up complications, and length of follow-up were reviewed. Infection complications were defined as cellulitis requiring treatment with intravenous or oral antibiotics, patients requiring operative debridement after definitive fixation, and documentation of osteomyelitis. RESULTS In the fasciotomy group, two patients developed cellulitis that was treated with a short course on oral antibiotics. There were no documented deep infections. In the no fasciotomy group, eight patients (6.25%) had a documented culture-positive deep infection. Additionally, six patients had documented occurrences of cellulitis managed with oral or intravenous antibiotics. CONCLUSIONS Definitive internal fixation of tibial plateau fractures in the presence of open fasciotomy wounds does not seem to be associated with an increased infection risk.
Covariance of Isometric and Dynamic Arm Contractions: Multivariate Genetic Analysis

Abstract The purpose of the present study was to examine genetic and environmental contributions to individual differences in maximal isometric, concentric and eccentric muscle strength and muscle cross-sectional area (MCSA) of the elbow flexors. A generality versus specificity hypothesis was explored to test whether the 4 strength variables share a genetic component or common factors in the environment or whether the genetic/environmental factors are specific for each strength variable. The 4 variables under study were measured in 25 monozygotic and 16 dizygotic male Caucasian twin pairs (22.4 ± 3.7 years). The multivariate genetic analyses showed that all 4 variables shared a genetic and environmental component, which accounted for 43% and 6% in MCSA (h2 = 81%), 47% and 20% in eccentric (h2 = 65%), 58% and 4% in isometric (h2 = 70%) and 32% and 1% in concentric strength (h2 = 32%) respectively. The remaining variation was accounted for by contraction type specific and muscle cross-sectional area specific genetic and environmental effects, which accounted for 38% and 14% in MCSA, 18% and 15% in eccentric, 12% and 26% in isometric and 0% and 67% in concentric strength respectively. This exploratory multivariate study suggests shared pleiotropic gene action for MCSA, eccentric, isometric and concentric strength, with a moderate to high genetic contribution to the variability of these characteristics.
Measles-mumps-rubella Vaccination and Egg Allergy

There has been long standing concern about the safety of measles-mumps-rubella vaccine in children with history of egg allergy. We review our experience in vaccinating such children in our hospital over a four- year period. Clinical evidences on the risk of anaphylactic reaction after measles-mumps-rubella vaccination is reviewed. A revised recommendation for the vaccination of children with history of egg allergy is proposed.
Evaluation of Sanofi Diagnostics Pasteur Chlamydia Microplate EIA shortened assay and comparison with cell culture and Syva Chlamydia MicroTrak II EIA in high- and low-risk populations

Seven hundred thirty-two female urogenital samples were collected for Chlamydia trachomatis testing by both the Sanofi Diagnostics Pasteur (Chaska, Minn.) Chlamydia Microplate EIA by the shortened protocol and the Syva (San Jose, Calif.) MicroTrak II EIA, and the results were compared with those obtained by cell culture. For the analysis of samples from female patients, the patients were divided into high- and low-risk categories. An additional 121 male urethral samples were collected and tested by the Sanofi Microplate EIA and cell culture; for the analysis of samples from male patients, the patients were divided into asymptomatic and symptomatic categories. All specimens positive by enzyme immunoassay (EIA) were confirmed by a blocking assay following the respective manufacturer's instructions. Specimens negative by EIA that fell within a gray zone 30% below the cutoff and negative cultures with one or more corresponding positive EIA results were tested further by cytocentrifugation and direct immunofluorescent assay. The overall sensitivity, specificity, positive predictive value, and negative predictive value for Syva versus culture were 94, 98.8, 85.5 and 99.6%, respectively. After resolution, the results were 94.5, 99.6, 94.5, and 99.6%, respectively. The parallel results for the Sanofi Microplate EIA versus culture were 94.0, 98.7, and 83.9, and 99.6%, respectively, and after being resolved, the results were 94.9, 100, 100, and 99.6%, respectively. In the small male population tested, the resolved results of the Sanofi Microplate EIA versus culture demonstrated sensitivity, specificity, positive predictive value, and negative predictive value of 100, 100, 100, and 100%, respectively. The present study demonstrated that the Sanofi Microplate EIA shortened protocol is highly sensitive and specific in comparison with cell culture and the Syva MicroTrak II EIA.
Pharmacokinetics of FCE 22891, a new oral penem

FCE 22891 is the oral prodrug of FCE 22101, a new broad-spectrum penem. The pharmacokinetics of FCE 22891 after single-dose administration, its absolute bioavailability, and the effect of food intake on its absorption were investigated in three different randomized crossover studies in healthy volunteers. Drug levels in blood and urine were measured by high-pressure liquid chromatography and bioassay. For optimal comparison of the results of all studies, and since there was good agreement of both methods, only the high-pressure liquid chromatography results are included. The pharmacokinetics of the penem were linear, and its bioavailability after oral administration was 42 +/- 11%. Food intake increased the total area under the curve from 0 h to infinity from 11.9 +/- 3.5 to 14.1 +/- 2.4 mg.h/liter. A specific side effect, i.e., bladder complaints, was registered in some volunteers taking FCE 22891 at doses greater than or equal to 1.0 g.
Soft-x-ray-absorption studies of the location of extra charges induced by substitution in controlled-valence materials.

We present high-resolution 2p x-ray-absorption spectra from 3d transition metals M in three series of pseudobinary and pseudoternary oxides. We show how the detailed shape of the multiplet within the spectra can be used to determine the valence of the M ions. The spectra of the early-transition-metal compounds show dramatic changes as a function of substitution due to changes in the M 3d occupancy, indicating that the extra holes or electrons are located predominantly at the 3d-metal sites. This contrasts strongly with the behavior of the spectra of late-transition-metal compounds, for which the extra charges induced by substitution go to oxygen states.