Call, challenge, and reformation

Preached at Edmonton, Alta, O 28 2001

Insights into antibody catalysis: Structure of an oxygenation catalyst at 1.9-Å resolution

The x-ray crystal structures of the sulfide oxidase antibody 28B4 and of antibody 28B4 complexed with hapten have been solved at 2.2-Å and 1.9-Å resolution, respectively. To our knowledge, these structures are the highest resolution catalytic antibody structures to date and provide insight into the molecular mechanism of this antibody-catalyzed monooxygenation reaction. Specifically, the data suggest that entropic restriction plays a fundamental role in catalysis through the precise alignment of the thioether substrate and oxidant. The antibody active site also stabilizes developing charge on both sulfur and periodate in the transition state via cation-pi and electrostatic interactions, respectively. In addition to demonstrating that the active site of antibody 28B4 does indeed reflect the mechanistic information programmed in the aminophosphonic acid hapten, these high-resolution structures provide a basis for enhancing turnover rates through mutagenesis and improved hapten design

Neuronal Distortions of Reward Probability without Choice

Reward probability crucially determines the value of outcomes. A basic phenomenon, defying explanation by traditional decision theories, is that people often overweigh small and underweigh large probabilities in choices under uncertainty. However, the neuronal basis of such reward probability distortions and their position in the decision process are largely unknown. We assessed individual probability distortions with behavioral pleasantness ratings and brain imaging in the absence of choice. Dorsolateral frontal cortex regions showed experience dependent overweighting of small, and underweighting of large, probabilities whereas ventral frontal regions showed the opposite pattern. These results demonstrate distorted neuronal coding of reward probabilities in the absence of choice, stress the importance of experience with probabilistic outcomes and contrast with linear probability coding in the striatum. Input of the distorted probability estimations to decision-making mechanisms are likely to contribute to well known inconsistencies in preferences formalized in theories of behavioral economics

Navigation/traffic control satellite mission study. Volume 2 - Systems analyses

Systems analysis of spacecraft network for transoceanic traffic contro

Development and Evaluation of Titanium Spacesuit Bearings

The Z-2 Prototype Planetary Extravehicular Space Suit Assembly is a continuation of NASA's Z-series of spacesuits, designed with the intent of meeting a wide variety of exploration mission objectives, including human exploration of the Martian surface. Incorporating titanium bearings into the Z-series space suit architecture allows us to reduce mass by an estimated 23 lbs per suit system compared to the previously used stainless steel bearing race designs, without compromising suit functionality. There are two obstacles to overcome when using titanium for a bearing race- 1) titanium is flammable when exposed to the oxygen wetted environment inside the space suit and 2) titanium's poor wear properties are often challenging to overcome in tribology applications. In order to evaluate the ignitability of a titanium space suit bearing, a series of tests were conducted at White Sands Test Facility (WSTF) that introduced the bearings to an extreme test profile, with multiple failures imbedded into the test bearings. The testing showed no signs of ignition in the most extreme test cases; however, substantial wear of the bearing races was observed. In order to design a bearing that can last an entire exploration mission (approx. 3 years), design parameters for maximum contact stress need to be identified. To identify these design parameters, bearing test rigs were developed that allow for the quick evaluation of various bearing ball loads, ball diameters, lubricants, and surface treatments. This test data will allow designers to minimize the titanium bearing mass for a specific material and lubricant combination and design around a cycle life requirement for an exploration mission. This paper reviews the current research and testing that has been performed on titanium bearing races to evaluate the use of such materials in an enriched oxygen environment and to optimize the bearing assembly mass and tribological properties to accommodate for the high bearing cycle life for an exploration mission

Prescribing of psychotropic medications to the elderly population of a Canadian province: a retrospective study using administrative databases

Background. Psychotropic medications, in particular second-generation antipsychotics (SGAs) and benzodiazepines, have been associated with harm in elderly populations. Health agencies around the world have issued warnings about the risks of prescribing such medications to frail individuals affected by dementia and current guidelines recommend their use only in cases where the benefits clearly outweigh the risks. This study documents the use of psychotropic medications in the entire elderly population of a Canadian province in the context of current clinical guidelines for the treatment of behavioural disturbances. Methods. Prevalent and incident utilization of antipsychotics, benzodiazepines and related medications (zopiclone and zaleplon) were determined in the population of Manitobans over age 65 in the time period 1997/98 to 2008/09 fiscal years. Comparisons between patients living in the community and those living in personal care (nursing) homes (PCH) were conducted. Influence of sociodemographic characteristics on prescribing was assessed by generalized estimating equations. Non-optimal use was defined as the prescribing of high dose of antipsychotic medications and the use of combination therapy of a benzodiazepine (or zopiclone/zaleplon) with an antipsychotic. A decrease in intensity of use over time and lower proportions of patients treated with antipsychotics at high dose or in combination with benzodiazepines (or zopiclone/zaleplon) was considered a trend toward better prescribing. Multiple regression analysis determined predictors of non-optimal use in the elderly population. Results. A 20-fold greater prevalent utilization of SGAs was observed in PCH-dwelling elderly persons compared to those living in the community. In 2008/09, 27% of PCH-dwelling individuals received a prescription for an SGA. Patient characteristics, such as younger age, male gender, diagnoses of dementia (or use of an acetylcholinesterase inhibitor) or psychosis in the year prior the prescription, were predictors of non-optimal prescribing (e.g., high dose antipsychotics). During the period 2002/3 and 2007/8, amongst new users of SGAs, 10.2% received high doses. Those receiving high dose antipsychotics did not show high levels of polypharmacy. Conclusions. Despite encouraging trends, the use of psychotropic medications remains high in elderly individuals, especially in residents of nursing homes. Clinicians caring for such patients need to carefully assess risks and benefits