Marker selection for the transmission/disequilibrium test, in recently admixed populations

Various analytical, iterative and rebinning algorithms have been proposed for 3D reconstruction in positron emission tomography. This paper examines execution times of five analytical and rebinning algorithms. Meaningful comparisons are obtained by using similar software modules in all implementations. Reconstruction times are shown to differ by vast amounts: the Favor algorithm of Defrise et al is more than twice as fast as the widely used reprojection algorithm of Kinahan and Rogers; the Fourier rebinning algorithm (Fore) recently developed by Defrise is more than 15 times faster than the reprojection algorithm.     

Overexpression of human superoxide dismutase inhibits oxidation of low-density lipoprotein by endothelial cells

Oxidation of LDL in the subendothelial space has been proposed to play a key role in atherosclerosis. Endothelial cells produce superoxide anions (O2.-) and oxidize LDL in vitro; however, the role of O2.- in endothelial cell-induced LDL oxidation is unclear. Incubation of human LDL (200 microg/mL) with bovine aortic endothelial cells (BAECs) for 18 hours resulted in a 4-fold increase in LDL oxidation compared with cell-free incubation (22.5+/-1.1 versus 6.3+/-0.2 [mean+/-SEM] nmol malondialdehyde/mg LDL protein, respectively; P<0.05). Under similar conditions, incubation of LDL with porcine aortic endothelial cells resulted in a 5-fold increase in LDL oxidation. Inclusion of exogenous copper/zinc superoxide dismutase (Cu/ZnSOD, 100 microg/mL) in the medium reduced BAEC-induced LDL oxidation by 79%. To determine whether the intracellular SOD content can have a similar protective effect, BAECs were infected with adenoviral vectors containing cDNA for human Cu/ZnSOD (AdCu/ZnSOD) or manganese SOD (AdMnSOD). Adenoviral infection increased the content and activity of either Cu/ZnSOD or MnSOD in the cells and reduced cellular O2.- release by two thirds. When cells infected with AdCu/ZnSOD or AdMnSOD were incubated with LDL, formation of malondialdehyde was decreased by 77% and 32%, respectively. Two other indices of LDL oxidation, formation of conjugated dienes and increased LDL electrophoretic mobility, were similarly reduced by SOD transduction. These data suggest that production of O2.- contributes to endothelial cell-induced oxidation of LDL in vitro. Furthermore, adenovirus-mediated transfer of cDNA for human SOD, particularly Cu/ZnSOD, effectively reduces oxidation of LDL by endothelial cells.     

Recombinant modified vaccinia virus Ankara-simian immunodeficiency virus gag pol elicits cytotoxic T lymphocytes in rhesus monkeys detected by a major histocompatibility complex class I/peptide tetramer

The utility of modified vaccinia virus Ankara (MVA) as a vector for eliciting AIDS virus-specific cytotoxic T lymphocytes (CTL) was explored in the simian immunodeficiency virus (SIV)/rhesus monkey model. After two intramuscular immunizations with recombinant MVA-SIVSM gag pol, the monkeys developed a Gag epitope-specific CTL response readily detected in peripheral blood lymphocytes by using a functional killing assay. Moreover, those immunizations also elicited a population of CD8+ T lymphocytes in the peripheral blood that bound a specific major histocompatibility complex class I/peptide tetramer. These Gag epitope-specific CD8+ T lymphocytes also were demonstrated by using both functional and tetramer-binding assays in lymph nodes of the immunized monkeys. These observations suggest that MVA may prove a useful vector for an HIV-1 vaccine. They also suggest that tetramer staining may be a useful technology for monitoring CTL generation in vaccine trials in nonhuman primates and in humans.     

Role of orlistat in the treatment of obese patients with type 2 diabetes. A 1-year randomized double-blind study

OBJECTIVE: Obesity is an important risk factor for type 2 diabetes. Weight loss in patients with type 2 diabetes is associated with improved glycemic control and reduced cardiovascular disease risk factors, but weight loss is notably difficult to achieve and sustain with caloric restriction and exercise. The purpose of this study was to assess the impact of treatment with orlistat, a pancreatic lipase inhibitor, on weight loss, glycemic control, and serum lipid levels in obese patients with type 2 diabetes on sulfonylurea medications. RESEARCH DESIGN AND METHODS: In a multicenter 57-week randomized double-blind placebo-controlled study, 120 mg orlistat or placebo was administered orally three times a day with a mildly hypocaloric diet to 391 obese men and women with type 2 diabetes who were aged > 18 years, had a BMI of 28-40 kg/m2, and were clinically stable on oral sulfonylureas. Changes in body weight, glycemic control, lipid levels, and drug tolerability were measured. RESULTS: After 1 year of treatment, the orlistat group lost 6.2 +/- 0.45% (mean +/- SEM) of initial body weight vs. 4.3 +/- 0.49% in the placebo group (P < 0.001). Twice as many patients receiving orlistat (49 vs. 23%) lost > or = 5% of initial body weight (P < 0.001). Orlistat treatment plus diet compared with placebo plus diet was associated with significant improvement in glycemic control, as reflected in decreases in HbA1c (P < 0.001) and fasting plasma glucose (P < 0.001) and in dosage reductions of oral sulfonylurea medication (P < 0.01). Orlistat therapy also resulted in significantly greater improvements than placebo in several lipid parameters, namely, greater reductions in total cholesterol, (P < 0.001), LDL cholesterol (P < 0.001), triglycerides (P < 0.05), apolipoprotein B (P < 0.001), and the LDL-to-HDL cholesterol ratio (P < 0.001). Mild to moderate and transient gastrointestinal events were reported with orlistat therapy, although their association with study withdrawal was low. Fat-soluble vitamin levels generally remained within the reference range, and vitamin supplementation was required in only a few patients. CONCLUSIONS: Orlistat is an effective treatment modality in obese patients with type 2 diabetes with respect to clinically meaningful weight loss and maintenance of weight loss, improved glycemic control, and improved lipid profile.     

Transforming growth factor beta: a matter of life and death

A wide variety of functions, many of which represent opposing activities, have been attributed to TGF-beta, a molecule implicated in embryogenesis, development, and immune and inflammatory processes. This paradoxical behavior of promoting or inhibiting cell growth and function, while important in normal physiology and homeostasis, can contribute to or interrupt pathologic sequelae, making TGF-beta a particularly intriguing molecule for study. New transgenic mouse models displaying targeted alterations in TGF-beta 1 expression offer novel and unique opportunities to determine the essential function(s) of TGF-beta.     

Bridging temporal gaps between CS and US in autoshaping: Insertion of other stimuli before, during, and after CS.

In 4 experiments, female White Carneaux pigeons were exposed to key-light illuminations separated from food delivery by 12–60 sec. Approach to the key light did not develop on conventional trace-conditioning arrangements but occurred consistently whenever some auditory or visual stimulus filled the CS–UCS gap (serial conditioning) or was always present except during the gap. The CS approach was strong only when the stimulus present during the intertrial interval remained on until the termination of CS; if the stimulus ended at CS onset, conditioning did not occur. Although discriminability of CS–UCS gaps from intertrial periods seemed necessary for conditioning to occur in the absence of close CS–UCS contiguity, the outcome of the final experiment indicates that such discriminability was not sufficient for conditioning. Results are discussed in terms of possible 2nd-order conditioning effects and the changes in the associative strength of the "local context" existing when the CS appears, which may lead to superconditioning of CS. (35 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relationship of gas phase mass transfer to thermal conductivity of refractories

The problem of change in thermal resistance of pores and microcracks in refractories with occurrence of heterogeneous reactions and formation of gas with diffusion product transfer in the temperature gradient field is analyzed.Translated from Inzhenerno-Fizicheskii Zhurnal, Vol. 34, No. 3, pp. 452–455, March, 1978.     

Another stabilized generator model for three phase sinewaves

A new three dimensional oscillator for generating three phases of sinewaves is derived. The model is similar to the previous ones (Ref. 1 and 2) in enabling an undistorted stabilized generation of sinewaves. It possesses certain advantages in comparison to the previous models. The oscillator appears as a viable model for representing synchronous generators in a simplified manner in the simulation of power systems.