Endothelin-1 infusion inhibits plasma insulin responsiveness in normal men

OBJECTIVES: Elevated plasma endothelin (ET)-1 levels have been described in insulin-resistant states such as syndrome X, obesity, non-insulin-dependent diabetes mellitus, and in some studies in essential hypertension. To investigate whether increases in circulating ET-1 to levels observed in insulin-resistant states can modulate insulin levels and/or insulin sensitivity in humans, we assessed these variables during low, non-pressor-dose ET-1 compared with placebo infusion. DESIGN: In a randomized, single blind, crossover design, 10 lean normotensive male subjects received either an intravenous infusion of subpressor doses of ET-1 dissolved in polygeline or a control infusion of polygeline only (placebo). Using dynamic assessment by the minimal model approach with the modified frequent sampling intravenous glucose tolerance test (FSIGT) the following and other parameters were measured: insulin sensitivity; acute insulin response to glucose (AIR(G)) calculated as the average of the three peak values between 2 and 5 min after injection of glucose from which the basal insulin levels were subtracted; the initial area under the curve (AUC(1-19)) from insulin values between time 0 and 19 min and the first-phase insulin secretion (phi1) from insulin kinetics parameters. RESULTS: ET-1 infusion reduced AIR(G) (to 34.85 +/- 4.27 compared with 49.3 +/- 6.9 microU/ml during placebo, P=0.017) and the acute C-peptide response to glucose (to 2.33 +/- 0.41 compared with 3.1 +/- 0.44 ng/ml, P=0.018), decreased plasma insulin levels during the FSIGT compared with placebo (analysis of variance P<0.0001) and decreased the AUC(1-19) (to 2.1 +/- 0.2 compared with 2.9 +/- 0.3 U/l per 20 min, P<0.01) while phi1 tended to be lower. S1 measured during ET-1 infusion was unaltered (11.11 +/- 1.91 x 10(-4) versus 10.88 +/- 2.11 10(-4)/min per mU per l, NS). CONCLUSIONS: These findings demonstrate that an increase in circulating ET-1 to levels observed in insulin-resistant states acutely diminishes the insulin secretory response but does not significantly modify insulin sensitivity.     

On-Line Shape recognition with incremental training using binary synaptic weights algorithm

Recognition of hand drawn shapes is beneficial in drawing packages and automated sketch entry in handheld computers. In this paper, we propose a new approach to on-line geometric shape recognition with incremental training function, which utilizes a heuristic function to reduce noise and a neural network for classification and on-line training. Instead of recognizing segments of a drawing and then performing syntactical analysis to match with a predefined shape, which is weak in terms of generalization and dealing with noise, we examine the shape as a whole. The main concept of the recognition method is derived from the fact that internal angles are very important in the perceived shape of outlines. Our application's aim is to recognize elliptic, rectangular, and triangular shapes in a way similar to human cognition of these shapes. Human beings recognize such basic shapes regardless of the variations in size, noise on the shape border, rotation and in the case of triangles, regardless of the type of the triangle. The key concept is that the neural network learns the relationships between the internal angles of a shape and its classification, therefore only a few training samples which represent the class of the shape are sufficient. Fast meremental training, which is performed on-line, is accomplished by the use of the Binary Synaptic Weights algorithm, a one pass, feedforward neural network training algorithm. Incremental training offers the advantage of adjusting the recognition capability of the system to the user's drawings. the results are very successful, such that the neural network correctly classified shapes that did not have any resemblance to the shapes in the initial training set.     

A CCG repeat polymorphism adjacent to the CAG repeat in the Huntington disease gene: implications for diagnostic accuracy and predictive testing

STUDY HYPOTHESIS: Concentrated aqueous solutions of hydroxocobalamin (OHCob) are given intravenously for the treatment of cyanide poisoning. Because OHCob solutions are intensely red and have peak light absorptions at 352 nm and 525 nm, we investigated whether the presence of OHCob in serum would interfere with various automated, colorimetric chemistry measurements. DESIGN: Selected serum chemistry colorimetric measurements were compared in seven patients, using their own serum as control, with serum containing OHCob at the following concentrations: 100 mg/L, 500 mg/L, and 1,000 mg/L. These concentrations are in the range achieved with therapeutic doses of OHCob when given for cyanide poisoning. MEASUREMENTS AND MAIN RESULTS: Statistically significant alterations in serum values for aspartate aminotransferase, total bilirubin, creatinine, magnesium, and iron were seen in the presence of OHCob. CONCLUSION: The presence of OHCob in serum interferes with several chemistry methodologies, and such interference should be anticipated when this antidote is used.     

Roles of word frequency and age of acquisition in word naming and lexical decision.

Six experiments are reported that contrasted the effects of frequency and age of acquisition on written word recognition. Age of acquisition affected word-naming speed when frequency was controlled (Experiment 1), but there was no effect of frequency when age of acquisition was controlled (Experiment 2). Experiments 3 and 4 found an effect of age of acquisition upon immediate but not delayed naming speed, but no frequency effect on either immediate or delayed naming once age of acquisition was controlled. Independent effects of frequency and age of acquisition were observed in the lexical decision task (Experiments 5 and 6). Implications for theoretical accounts of word recognition and the possible roles of age of acquisition and frequency in word recognition are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Carbon fibre composites based on polyimide/silica ceramers: aspects of structure-properties relationship

Polyimide/silica ceramers, based on the products of the hydrolysis of tetraethoxysilane (TEOS) and a commercial poly(amic acid) solution, were used to fabricate unidirectional carbon fibre composites, which were subsequently evaluated with respect to thermal and mechanical properties. There is evidence to suggest that the silica component of these ceramers is present as dispersed discrete particles at low silica concentration (i.e. 7 wt%) and as fine interconnected domains trapped within the polyimide matrix at higher silica content (i.e. 14 wt%). The dimensions of the silica domains were in the region of 7–20 nm. Carbon fibre composites produced from ceramer solutions (CF/ceramers) were found to exhibit lower thermal expansion and a greater retention of flexural and interlaminar shear properties at elevated temperature than the corresponding polyimide-matrix composites (CF/polyimide). The properties of CF/ceramers were generally better for systems containing the higher amount of silica and were improved further by lowering the pH value of the precursor ceramer solution. This is believed to have resulted from the enhanced fluidity of the ceramer gel within the pre-impregnated fibres, giving rise to a higher packing density of the fibres and a more homogeneous distribution of fibres. CF/ceramers were also found to exhibit a better thermal oxidative stability at 350°C than the corresponding CF/polyimide, although a substantial amount of porosity developed in the case of ceramers with the higher silica content.     

Dynex: multiplex ELISA technology

Conventional enzyme-linked immunosorbent assay (ELISA) is a gold standard for screening antibodies and testing for protein or antigen presence. A significant limitation of this assay resides in the fact that only one analyte can be assessed per microplate well. Here, we describe and investigate a new technology consisting of an automated ELISA system in which up to 10 analytes can be measured within one single well, thus improving productivity, accuracy, and repeatability by reducing the amount of human labor required. Another strength of the platform is that a user can load any necessary sets/subsets of beads to perform required assays, with improved flexibility compared to manufactured-loaded arrays for multiplex analysis. We also demonstrate that this system can be used to determine the pathogenicity (i.e., presence of Shiga toxins) and serotype (i.e., Escherichia coli O157) of E. coli isolates.     

Groundwater-surface water interactions and agricultural nutrient transport in a Great Lakes clay plain system

Nutrient export from agricultural land to surface waters is a significant environmental concern within the Great Lakes Basin (GLB). A field-based watershed-scale study was completed to investigate spatial and temporal variations of phosphorus and nitrate to assess nutrient transport pathways and groundwater-surface water interactions in an agriculturally dominated clay plain system. This was conducted in the 127 km² Upper Parkhill Watershed, near Lake Huron in southwestern Ontario, Canada. Data collection occurred from June 2018 to May 2019 via continuous sensor deployment and discrete sampling of stream water, groundwater, hyporheic zone, and tile drainage water. Samples were analyzed for various nutrient species (total, total dissolved, soluble reactive, and particulate phosphorus, and nitrate-N) to examine the hydrological dynamics of principal transport pathways of agriculturally-derived nutrients. Total phosphorus and nitrate concentrations in stream water ranged from 0.007 to 0.324 mg/L and 0.32 to 13.13 mg NO₃^?-N/L, respectively. Tile drainage water total phosphorous concentrations varied from 0.006 to 0.066 mg/L. Groundwater total dissolved phosphorus concentrations ranged from <0.003 to 0.085 mg/L. Transport of phosphorus through tile drainage was observed to be greater than through groundwater over the study period. No distinct relationship was observed between nutrient concentrations in the hyporheic zone and the vertical hydraulic gradient within this zone in the studied stream reach. Preliminary correlations were discerned between water quality observations and recognized land management practices. Given the elevated stream nutrient concentrations, these results are consequential for the continual improvement of strategies and programs devised to conserve water resources within the GLB.     

Probabilistic heuristic estimates

Though they constitute the major knowledge source in problem-solving systems, no unified theory of heuristics has emerged. Pearl [15] defines heuristics as criteria, methods, or principles for deciding which among several alternative courses of action promises to be the most effective in order to achieve some goal. The absence of a more precise definition has impeded our efforts to understand, utilize, and discover heuristics. Another consequence is that problem-solving techniques which rely on heuristic knowledge cannot be relied upon to act rationally — in the sense of the normative theory of rationality.To provide a sound basis for BPS, the Bayesian Problem-Solver, we have developed a simple formal theory of heuristics, which is general enough to subsume traditional heuristic functions as well as other forms of problem-solving knowledge, and to straddle disparate problem domains. Probabilistic heuristic estimates represent a probabilistic association of sensations with prior experience — specifically, a mapping from observations directly to subjective probabilities which enables the use of theoretically principled mechanisms for coherent inference and decision making during problem-solving. This paper discusses some of the implications of this theory, and describes its successful application in BPS.This research was made possible by support from Heuristicrats, the National Aeronautics and Space Administration, and the Rand Corporation.