Clinical assessment applications of ambulatory biosensors.

Ambulatory biosensor assessment includes a diverse set of rapidly developing and increasingly technologically sophisticated strategies to acquire minimally disruptive measures of physiological and motor variables of persons in their natural environments. Numerous studies have measured cardiovascular variables, physical activity, and biochemicals such as cortisol in psychopathology and treatment research. The physiological concomitants of many behavior and medical disorders and the benefits of a multimethod assessment strategy provide strong rationales for clinical applications of ambulatory biosensor measurement. A number of psychometric dimensions of evaluation are important in clinical applications of biosensor measurement, including accuracy and validity, reliability and consistency, clinical utility, incremental validity and utility, sensitivity to change, generalizability, cost benefits, and the conditional nature of dimensions of biomeasure evaluation. The authors review ambulatory biosensor methods and make recommendations for use of the technology. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Visualization and debugging of distributed multiagent systems

Visualizing the behavior of systems with distributed data, control, and process is a notoriously difficult task. Each component in the distributed system has only a local view of the whole setup, and the onus is on the user to integrate, into a coherent whole, the large amounts of limited information they provide. In this article, we describe an architecture and an implemented system for visualizing and controlling distributed multiagent applications. The system comprises a suite of tools, with each tool providing a different perspective of the application being visualized . Each tool interrogates the components of the distributed application, collates the returned information, and presents this information to users in an appropriate manner. This in essence, shifts the burden ofinference from the user to the visualizer. Our visualizer has been evaluated on four distributed multiagent systems: a travel management application, a telecommunications network management application, a business process management demonstrator, and an electronic commerce application. Lastly, we briefly show how the suite of tools can be used together for debugging multiagent applications - a process we refer to as debugging via corroboration.     

Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice

The function of the central cannabinoid receptor (CB1) was investigated by invalidating its gene. Mutant mice did not respond to cannabinoid drugs, demonstrating the exclusive role of the CB1 receptor in mediating analgesia, reinforcement, hypothermia, hypolocomotion, and hypotension. The acute effects of opiates were unaffected, but the reinforcing properties of morphine and the severity of the withdrawal syndrome were strongly reduced. These observations suggest that the CB1 receptor is involved in the motivational properties of opiates and in the development of physical dependence and extend the concept of an interconnected role of CB1 and opiate receptors in the brain areas mediating addictive behavior.     

Cell surface regulators of complement, 5I2 antigen, and CD59, in the rat eye and adnexal tissues

PURPOSE: Cell surface complement regulatory proteins have been identified in high levels in ocular tissues, but no experimental model is available for examining their physiological roles. To develop such a model, the distribution of 5I2 antigen, a protein possessing the functions of the human decay-accelerating factor (DAF [CD55]) and membrane cofactor protein (MCP [CD46]), and rat inhibitory protein (CD59), the homologue of the human membrane inhibitor of reactive lysis (MIRL[CD59]) were characterized in the rat eye and ocular adnexal structures. METHODS: After euthanasia of female Wistar rats, followed by orbital exenteration, eyelids and orbital tissue including the lacrimal gland were separated from the globes and immediately snap-frozen in liquid nitrogen at -70 degrees C. Tissues then were sectioned at -20 degrees C and examined immunohistochemically for 5I2 antigen and rat CD59. RESULTS: Both molecules were found to be present in high levels in multiple sites. Corneal and conjunctival epithelia showed moderate to intense labeling for both regulators. Fibroblasts in the corneal stroma, conjunctiva, and sclera labeled similarly. Corneal endothelial cells showed intense labeling for rat CD59 but not for 5I2 antigen. The iris and ciliary body showed intense labeling for both proteins. The retina showed labeling at multiple levels, with that of rat CD59 being more intense than that of 5I2 antigen. The lacrimal gland labeled for both regulators. Vessels, muscle, and nerves in the orbit labeled intensely for both antigens. In the eyelid, conjunctiva, sebaceous glands, and muscle and nerve tissues labeled moderately to intensely for both molecules, whereas skin epithelium labeled less intensely. CONCLUSIONS: 5I2 antigen and rat CD59 are expressed in high levels and distributed similarly in the rat eye and lacrimal gland to DAF, MCP, and MIRL in the human eye and lacrimal gland. These findings establish the rat ocular surface as a model for studying the role of cell surface complement regulators in this site. This first identification of copious expression of these proteins in eyelid structures, which also participate in protection of the ocular surface, further suggests an important role for surface complement regulatory proteins in this location.     

Diffusion and transfer of antibody proteins from a sugar-based hydrogel

Diffusion of antibody protein from hydrogel films and hydrogel encapsulated in a microcapillary was studied. Thin hydrogel films were formed by crosslinking 6-acryloyl-B-O-methylgalactoside with N,N'-methylene-bis-acrylamide and the diffusive transport of monoclonal antimouse IgG-FITC into and out of the hydrate films was measured. Diffusion coefficients in 2 and 4% crosslinked hydrogel films were measured. The measured diffusion constants determined for IgG in both the 2 and 4% hydrogel films were comparable to the free diffusion of IgG in bulk water (Dmean approximately 10(-7) cm2/s). In addition, 2% crosslinked hydrogels were prepared in a capillary tube and the transport of antimouse IgG-FITC into and out of the hydrated hydrogel was measured. Kinetic analysis indicated that the protein transport through the capillary hydrogel was faster than would be expected for a simple diffusion process. Finally, by utilizing the diffusion of antibody from the capillary hydrogel, transfer of antibody to a silica surface was demonstrated. A capillary hydrogel loaded with antimouse IgG-FITC was used to transfer the protein to a silica surface forming a 30-micron spot of antibody, which was imaged using fluorescence microscopy. These results may lead to the development of a nonlithographic method of patterning antibodies on surfaces for use in integrated microimmunosensors.     

Use of cyclodextrins for manipulating cellular cholesterol content

Previous studies from this laboratory have demonstrated that exposure of tissue culture cells to cyclodextrins results in rapid cholesterol depletion. In the present study, we have developed experimental systems for using solutions of cyclodextrins, either 2-hydroxypropyl beta-cyclodextrin or methylated beta-cyclodextrin, complexed with varying amounts of free cholesterol to manipulate cell cholesterol content. Cholesterol delivered via the cyclodextrin has been found to be metabolically active, as measured by the acyl-coenzyme A:cholesterol acyltransferase (ACAT)-mediated esterification of [3H]cholesterol in Fu5AH rat hepatoma cells and Chinese hamster ovary cells. The methylated beta-cyclodextrin was found to be a more efficient donor in all cell types studied, with an average cholesterol uptake of at least 100 microg cholesterol/mg protein within 6 h. By modifying the cyclodextrin:cholesterol molar ratio, it is possible to manipulate the cellular cholesterol content of cells, producing conditions ranging from net cholesterol enrichment to depletion. The use of cyclodextrins provides a convenient, precise and reproducible method for modulating the cholesterol content of tissue culture cells.     

The reactions of nitromethane in the gas phase and on a Co-ZSM5 catalyst under the conditions of the methane/NOx SCR reaction

The rate of reaction of nitromethane in the gas phase is little changed by the presence of O₂ or NO. The major products are CO, NO and H₂O, plus NO₂ if O₂ is included. The corresponding catalytic reaction over fresh Co-ZSM5 commences at a much lower temperature and gives primarily CO₂ and NH₃, the latter being oxidised to N₂ above 340°C. As the catalyst ages below 320°C HNCO eventually becomes the major nitrogen-containing product although it can be hydrolysed by added water. The results demonstrate one possible route for the methane-SCR reaction. This revised version was published online in July 2006 with corrections to the Cover Date.     

A sensitivity assessment of uncertainty in infrastructure expansion

Under and overdesign is a major consideration in public infrastructure expansion. Traditional engineering economies of scale leading to overdesign errors must be counterbalanced by greater attention to high cost financing. Uncertainty in demand forecasting and in financial markets make decision tools which incorporate measures of information imperfection increasingly important. Further issues of overall social welfare make the question of short term and intergenerational equity major concerns. A rational expectations stochastic-analog of the conventional, present value, infrastructure expansion model has optimal overdesign properties. The problem is restated as a two-person, planner vs. future, social welfare game in a simple capital loss model. Sensitivity analysis shows the game-theoretic model which favors expansion underdesign is relatively less sensitive to greater demand forecast uncertainty than the rational expectations model.