Serum amyloid P component scintigraphy and turnover studies for diagnosis and quantitative monitoring of AA amyloidosis in juvenile rheumatoid arthritis

OBJECTIVE: To evaluate aspects of the natural history of AA amyloidosis complicating juvenile rheumatoid arthritis (JRA), and its response to therapy with chlorambucil. METHODS: Scintigraphy and 7-day turnover studies were performed in JRA patients with histologically proven (n = 35) or clinically suspected (n = 30) AA amyloidosis, following intravenous injection of 123I and 125I-labeled serum amyloid P component (SAP). Prospective monitoring studies were performed over 2-3 years in 20 patients with amyloidosis. All but 2 amyloidosis patients were treated with chlorambucil. RESULTS: Positive scanning results were obtained in all patients in whom imaging was performed within 12 years of positive biopsy findings of amyloid and in 5 patients with clinically suspected amyloidosis. Negative scanning results with normal SAP metabolism, indicating regression of amyloid, were obtained in 4 patients whose amyloidosis had been in full clinical remission for more than 12 years. Prospective monitoring studies in patients whose JRA-associated inflammatory activity was in remission demonstrated regression of amyloid in 8 patients and no substantial changes in 8 others; however, in 4 further patients with active inflammation, there was accumulation of amyloid. There was a very poor correlation between the amount of amyloid present at a particular site and the resultant organ dysfunction. CONCLUSION: Radiolabeled SAP scintigraphy and turnover studies are useful complementary tools in the diagnosis, screening, and quantitative monitoring of type AA amyloidosis in JRA. The amyloid deposits may progress and/or regress at different rates in different anatomic sites over short periods.     

Automated Parallelization of Discrete State-Space Generation

We consider the problem of generating a large state-space in a distributed fashion. Unlike previously proposed solutions that partition the set of reachable states according to a hashing function provided by the user, we explore heuristic methods that completely automate the process. The first step is an initial random walk through the state space to initialize a search tree, duplicated in each processor. Then, the reachability graph is built in a distributed way, using the search tree to assign each newly found state to classes assigned to the available processors. Furthermore, we explore two remapping criteria that attempt to balance memory usage or future workload, respectively. We show how the cost of computing the global snapshot required for remapping will scale up for system sizes in the foreseeable future. An extensive set of results is presented to support our conclusions that remapping is extremely beneficial.     

ACAT inhibitors derived from hetero-Diels-Alder cycloadducts of thioaldehydes

Acyl-CoA:cholesterol acyltransferase (ACAT) is the enzyme largely responsible for intracellular cholesterol esterification. A systemic inhibitor of ACAT is believed to be able to slow or even reverse the atherosclerotic process. Towards that goal, a series of cyclic sulfides, derived from the hetero-Diels-Alder reaction of thioaldehydes with 1,3-dienes, and bearing carboxamide substituents, were prepared and evaluated for in vitro (in several tissues and species) and ex vivo ACAT inhibition. Minor changes in subsequent structure were found to have a significant effect in optimization of the biological activity of this series of compounds.     

Path integral Monte Carlo simulations of the melting of molecular hydrogen surfaces

We have used Path Integral Monte Carlo to study the surface melting of molecular hydrogen. Density profiles perpendicular and parallel to the bare H₂ surface are computed showing the formation of a liquid adlayer at 6 K, less than half the bulk melting temperature of para-hydrogen, 13.8 K. To estimate the onset temperature and depth of H₂ surface melting we determine the static structure factor within the individual H₂-layers for wave vectors in the plane and find no crystalline order down to 3 K in a partially filled H₂ adlayer at the free surface. We find quantum effects amplify the melting point depression at the free H₂ surface compared to bulk by a factor of five over classical Lennard-Jones solids and find that the zero-point fluctuations of molecules at the surface are much enhanced over their bulk values. We see vacancy formation in the solid before melting.     

Adverse environmental conditions in the respiratory and medical ICU settings

Sleep deprivation and fragmentation occurring in the hospital setting may have a negative impact on the respiratory system by decreasing respiratory muscle function and ventilatory response to CO2. Sleep deprivation in a patient with respiratory failure may, therefore, impair recovery and weaning from mechanical ventilation. We postulate that light, sound, and interruption levels in a weaning unit are major factors resulting in sleep disorders and possibly circadian rhythm disruption. As an initial test of this hypothesis, we sampled interruption levels and continuously monitored light and sound levels for a minimum of seven consecutive days in a medical ICU, a multiple bed respiratory care unit (RCU) room, a single-bed RCU room, and a private room. Light levels in all areas maintained a day-night rhythm, with peak levels dependent on window orientation and shading. Peak sound levels were extremely high in all areas representing values significantly higher than those recommended by the Environmental Protection Agency as acceptable for a hospital environment. The number of sound peaks greater than 80 decibels, which may result in sleep arousals, was especially high in the intensive and respiratory care areas, but did show a day-night rhythm in all settings. Patient interruptions tended to be erratic, leaving little time for condensed sleep. We conclude that the potential for environmentally induced sleep disruption is high in all areas, but especially high in the intensive and respiratory care areas where the negative consequences may be the most severe.     

Genetic control of immunity to Heligmosomoides polygyrus: presentation of promiscuous antigens to parasite-specific T cell hybridomas

The role of MHC class II in the presentation of Heligmosomoides polygyrus antigens has been investigated, using a number of T cell hybridomas produced in A and E positive and negative mice. By using fixed and irradiated antigen presenting cells (APC), further evidence has emerged, to support earlier data, that there can be differential processing requirements during the presentation of H. polygyrus antigens by A and E molecules. In concordance with these earlier observations, this work provides further evidence than individual T cells can respond to antigen when presented by more than one MHC molecule. Previously, this evidence has been restricted to individual MHC molecules of the same haplotype, but these data show that H. polygyrus produces antigens which can be presented by both syngeneic and allogeneic MHC molecules. These antigens do not appear to be synonymous with the previously described H. polygyrus superantigen, as presentation is restricted to specific MHC haplotypes. It is proposed that H. polygyrus may produce these antigenic molecules as part of its strategy to manipulate the host immune system.     

Advancing controlled release packaging through smart blending

Researchers from Rutgers University and Clemson University have collaborated to develop a concept of using smart blending to generate functional packaging films for the controlled release of active compounds such as antimicrobials, antioxidants and flavour compounds to extend the shelf‐life of food. In this paper, literature results are reviewed to justify the significance of controlled release packaging (CRP) and the research gaps for further development are identified. A major research gap is the lack of packaging materials that can provide the release of active compounds at rates suitable for a wide range of food packaging applications. Smart blending is a promising technology for bridging this research gap. To fully realize the potentials of smart blending, a systematic approach for developing CRP using smart blending is also presented. Copyright © 2005 John Wiley & Sons, Ltd.     

PI control of discrete linear repetitive processes

Repetitive processes are a distinct class of 2D systems (i.e. information propagation in two independent directions) of both systems theoretic and applications interest. They cannot be controlled by direct extension of existing techniques from either standard (termed 1D here) or 2D systems theory. In this paper, we exploit their unique physical structure to show how two term, i.e. proportional plus integral (or PI) action, can be used to control these processes to produce desired behavior (as opposed to just stability).