Metabolism of carvedilol in dogs, rats, and mice

The excretion and biotransformation of carvedilol [1-[carbazolyl-(4)-oxy]-3-[(2-methoxyphenoxyethyl)amino]-2-p ropanol], a new, multiple-action, neurohormonal antagonist that exhibits the combined pharmacological activities of beta-adrenoreceptor antagonism, vasodilation, and antioxidation, were investigated in dogs, rats, and mice. Carvedilol was absorbed well, and biliary secretion was predominant in each species. Carvedilol was metabolized extensively in each species, and elimination of unchanged compound was minor in bile duct-catheterized rats and dogs. In dogs, glucuronidation of the parent compound and hydroxylation of the carbazolyl ring, with subsequent glucuronidation, were the major metabolic pathways. Rats showed the simplest metabolite profile; the primary metabolites were formed by hydroxylation of the carbazolyl ring, with subsequent glucuronidation. Mice displayed the most complicated metabolite profile; glucuronidation of the parent compound and hydroxylation of either the carbazolyl or phenyl ring, with subsequent glucuronidation, were the major metabolic routes. O-Dealkylation was a minor pathway in all species examined.     

Testing interval independence versus configural weighting using judgments of strength of preference.

Judges made choices and rated strengths of preference between gambles composed of 50–50 chances to receive either of 2 monetary outcomes (x, y). Others judged how much they would pay to play their chosen gamble rather than the other gamble. Judged strengths of preference violated interval independence, because they depended on the value of a common outcome. For example, judges offered to pay an average of $44 to play ($74, $100) instead of ($8, $100) but offered to pay only $24 to play ($6, $74) instead of ($6, $8). Results violated the theory that utility of gambles is a nonconfigural average of the values of the outcomes and that strengths of preference are monotonically related to utility differences. Results can be explained by a configural weight model in which the lowest outcome receives greater weight. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Uncertainty and sensitivity analysis for gas and brine migration at the Waste Isolation Pilot Plant: permeable shaft without panel seals

Latin hypercube sampling, partial correlation analysis, stepwise regression analysis and examination of scatterplots are used in conjunction with the BRAGFLO model in an uncertainty and sensitivity analysis of gas and brine movement at the Waste Isolation Pilot Plant. Topics investigated include (1) gas production due to corrosion of steel and microbial degradation of cellulosics, (2) gas saturation and pressure in the repository, (3) gas movement in anhydrite marker beds, and (4) gas and brine movement through a short, low permeability shaft seal to the Culebra Dolomite. Important variables identified in the analysis include initial brine saturation of the waste, stoichiometric terms for corrosion of steel and microbial degradation of cellulosics, corrosion and microbial degradation rates, porosity of the Salado Formation, transition (disturbed) zone porosity, marker bed (anhydrite) permeability, and seal permeability. Published by Elsevier Science Limited.     

Epitaxial Si-Ge etch stop layers with ethylene diamine pyrocatechol for bonded and etchback silicon-on-lnsulator

The etch rate in ethylene diamine pyrocatechol of Si_1-xGe_1-x (0.2 ≤ x< - 0.3) etch stops grown by molecular beam epitaxy was determined using Rutherford backscattering spectrometry. Etch rate selectivities as high as 390 were measured. Such etch stops allow for higher bonding temperatures than those possible with currently used boron-based etch stops. Defect etching was used to determine the maximal thickness of dislocation-free layers.     

Life cycle optimization of automobile replacement: model and application

Although recent progress in automotive technology has reduced exhaust emissions per mile for new cars, the continuing use of inefficient, higher-polluting old cars as well as increasing vehicle miles driven are undermining the benefits of this progress. As a way to address the "inefficient old vehicle" contribution to this problem, a novel life cycle optimization (LCO) model is introduced and applied to the automobile replacement policy question. The LCO model determines optimal vehicle lifetimes, accounting for technology improvements of new models while considering deteriorating efficiencies of existing models. Life cycle inventories for different vehicle models that represent materials production, manufacturing, use, maintenance, and end-of-life environmental burdens are required as inputs to the LCO model. As a demonstration, the LCO model was applied to mid-sized passenger car models between 1985 and 2020. An optimization was conducted to minimize cumulative carbon monoxide (CO), non-methane hydrocarbon (NMHC), oxides of nitrogen (NOx), carbon dioxide (CO2), and energy use over the time horizon (1985-2020). For CO, NMHC, and NOx pollutants with 12000 mi of annual mileage, automobile lifetimes ranging from 3 to 6 yr are optimal for the 1980s and early 1990s model years while the optimal lifetimes are expected to be 7-14 yr for model year 2000s and beyond. On the other hand, a lifetime of 18 yr minimizes cumulative energy and CO2 based on driving 12000 miles annually. Optimal lifetimes are inversely correlated to annual vehicle mileage, especially for CO, NMHC, and NOx emissions. On the basis of the optimization results, policies improving durability of emission controls, retiring high-emitting vehicles, and improving fuel economies are discussed.     

Semen fertility--an evaluation system for artificial insemination sires, technicians, herds, and systematic fixed effects

Semen fertility was evaluated on 4478 artificial insemination bulls using 2,007,520 breeding receipts for inseminations to 397,979 Holstein cows between January 1, 1978 and November 1, 1984 using mixed linear model methodology. Bulls differed on average by +/- 3.68% conception. Differences between herd-years ranged from 27.4 to -32.3% conception with an average difference of +/- 8.33%. Within herds, cow parity-service number accounted for the largest variation, ranging from 24.0% to -18.5% conception. June was the best month for conception (1.9) and January the poorest (-2.3), indicating effect of temperature and confinement in winter on estrous detection in the northeastern United States. Cows with intervals between repeat services of 21 d had conception rates 12% higher than intervals between repeat services of 11 d. Effect of month-year of semen collection varied by +/- 1.33% conception. Differences between technicians within years varied by +/- 3.37%. Results of the analysis indicate improved conception on dairy farms can be achieved by improved estrous detection, which is a major component of herd-year and service interval. Other components of the model contributed little to the variance in conception or are uncontrollable by farm management.     

Optimization of tannin-containing sorghum bran addition to gluten-free bread

Ingredients used to enhance sensory quality of gluten-free (GF) bread often lack in nutrients. This presents nutritional challenges for celiac-positive individuals and fails to meet expectations of healthfulness for non-celiac GF consumers. Sorghum (Sorghum bicolor L. Moench) flour can provide acceptable GF bread properties, and tannin-containing varieties contain antioxidants concentrated in the bran along with dietary fiber. Using a central composite design, tannin-containing sumac sorghum bran, gum (xanthan + guar), and water levels were optimized in a GF sorghum-based bread formulation. Loaf specific volume and gas cells/cm² were maximized while minimizing hardness and cell wall thickness. The optimum formulation containing 14.2% sorghum bran, 1% gum, and 145% water (flour basis) effectively increased dietary fiber in bread to 13.4% (considered “high fiber”) and showed oxygen radical absorbance capacity of 61.6 µmol TE/g. This optimum formulation did not differ from a sorghum flour-based control bread in consumers’ (N = 100) liking of color, texture, flavor, overall acceptability, nor willingness to buy (WTB). All mean hedonic scores (numbered 9-point scale) were above 5, whereas average WTB was 4.7 for the optimum formulation and 4.6 for the control (9-point Likert scale) among consumers varying in GF bread consumption habits. Perceived bread bitterness was low (averaging 2.85 on 9-point intensity scale), did not vary between samples despite marked differences in antioxidant capacity, and was not correlated with WTB. When utilizing effective optimization models with key functional ingredients, sumac sorghum bran addition can enhance dietary fiber and antioxidant potential in sorghum-based GF breads without compromising quality attributes.