Autoimmunity, immunodeficiency and mucosal infections: chronic intestinal inflammation as a sensitive indicator of immunoregulatory defects in response to normal luminal microflora

Despite the fact that target antigens and the genetic basis of several autoimmune diseases are now better understood, the initial events leading to a loss of tolerance towards self-components remain unknown. One of the most attractive explanations for autoimmune phenomena involves various infections as possible natural events capable of initiating the process in genetically predisposed individuals. The most accepted explanation of how infection causes autoimmunity is based on the concept of "molecular mimicry" (similarity between the epitopes of an autoantigen and the epitopes in the environmental antigen). Infectious stimuli may also participate in the development of autoimmunity by inducing an increased expression of stress proteins (hsp), chaperones and transplantation antigens, which leads to abnormal processing and presentation of self antigens. Superantigens are considered to be one of the most effective bacterial components to induce inflammatory reactions and to take part in the development and course of autoimmune mechanisms. It has long been known that defects in the host defense mechanism render the individual susceptible to infections caused by certain microorganisms. Impaired exclusion of microbial antigens can lead to chronic immunological activation which can affect the tolerance to self components. Defects in certain components of the immune system are associated with a higher risk of a development of autoimmune disease. The use of animal models for the studies of human diseases with immunological pathogenesis has provided new insights into the influence of immunoregulatory factors and the lymphocyte subsets involved in the development of disease. One of the most striking conclusion arising from work with genetically engineered immunodeficient mouse models is the existence of a high level of redundancy of the components of the immune system. However, when genes encoding molecules involved in T cell immunoregulatory functions are deleted, spontaneous chronic inflammation of the gut mucosa (similar to human inflammatory bowel disease) develops. Surprisingly, when such immunocompromised animals were placed into germfree environment, intestinal inflammation did not develop. Impairment of the mucosal immune response to the normal bacterial flora has been proposed to play a crucial role in the pathogenesis of chronic intestinal inflammation. The use of immunodeficient models colonized with defined microflora for the analysis of immune reactivity will shed light on the mode of action of different immunologically important molecules responsible for the delicate balance between luminal commensals, nonspecific and specific components of the mucosal immune system.     

Comparison of bond strengths of three denture base resins to treated nickel-chromium-beryllium alloy

The success of radiotherapy in eradicating tumours depends on the total radiation dose, but what limits this dose is the tolerance of the normal tissues within the treatment volume. Studies involving fibroblast survival have demonstrated the theoretical feasibility of a predictive assay of radiation sensitivity, but such an assay is still far from clinical application. Using pulsed-field gel electrophoresis (PFGE), we have quantified the initial "apparent" number of DNA double-strand breaks (dsb) induced by the radiation as an alternative measure of sensitivity in 2 different normal cell types from the same patients, epidermal skin cells and lymphocytes. We found significant inter-individual variation in the measured dsb (1-5 dsb/Gy/DNA unit). We also found a linear correlation between molecular damage in lymphocytes and skin samples from the same patient (slope = 0.83; r = 0.694; p = 0.0001). These results suggest that the initial number of dsb could be used as an indicator of the in vivo response to radiation.     

NIDA technical review: nitrite inhalants

Nitrite inhalants are commonly abused substances in the US and Europe. "Nitrite inhalants and AIDS" was a popular topic in the early 1980s when the cause of AIDS was not known. With the discovery of HIV, concern about nitrite use wained. However, nitrite inhalant use is associated with behavioral relapse and HIV transmission among gay men, with decreased lymphocyte counts and natural killer cell activity in laboratory studies, and remains a candidate "cofactor" in the pathogenesis of AIDS-related Karposi sarcoma. Discouraging nitrite use continues to be a worthwhile public health goal. Participants recommend specific research efforts.     

Randomness on Computable Probability Spaces—A Dynamical Point of View

We extend the notion of randomness (in the version introduced by Schnorr) to computable probability spaces and compare it to a dynamical notion of randomness: typicality. Roughly, a point is typical for some dynamic, if it follows the statistical behavior of the system (Birkhoff’s pointwise ergodic theorem). We prove that a point is Schnorr random if and only if it is typical for every mixing computable dynamics. To prove the result we develop some tools for the theory of computable probability spaces (for example, morphisms) that are expected to have other applications.     

Accelerating network applications by distributed interfaces on heterogeneous multiprocessor architectures

Hosts with several, possibly heterogeneous and/or multicore, processors provide new challenges and opportunities to accelerate applications with high communications bandwidth requirements. Many opportunities to scale these network applications with the increase in the link bandwidths are related to the exploitation of the available parallelism provided by the presence of several processing cores in the servers, not only for computing the workload of the user application but also for decreasing the overhead associated to the network interface and the system software.     

FAO’s AVHRR-based Agricultural Stress Index System (ASIS) for global drought monitoring

Agricultural production is highly dependent on climate variability in many parts of the world. In particular, drought may severely reduce crop yields, potentially affecting food availability at local, regional, and global scales. The Food and Agriculture Organization of the United Nations (FAO) operates the Global Early Warning System (GIEWS), which monitors global food supply and demand. One of the key challenges is to obtain synoptic information on a recurrent and timely basis about drought-affected agricultural zones. This is needed to quickly identify areas requiring immediate attention. The Agricultural Stress Index System (ASIS), based on imagery from the Advanced Very High Resolution Radiometer (AVHRR) sensors on board the National Oceanic and Atmospheric Administration (NOAA) and Meteorological Operational Satellite (METOP) satellites, was specifically developed to meet this need. The system is based on a methodology developed by Rojas, Vrieling, and Rembold over the African continent. This approach has been modified and adapted to the global scale to produce an agricultural stress index (ASI) representing, per administrative unit, the percentage of cropland (or pasture) areas affected by drought over the growing season. The vegetation health index (VHI), based on normalized difference vegetation index (NDVI) and temperature anomalies, is used as a drought indicator. A fused time series of AVHRR data from METOP and NOAA was used to produce a consistent time series of VHI at 1 km resolution. Global phenology maps, indicating the number of growing seasons and their start and end dates, were derived from a multi-annual image set of SPOT-Vegetation (1999–2011). The VHI time series and phenology maps were then combined to produce the ASI for the years 1984 to the present. This allowed evaluation of the suitability of the ASIS to identify drought using historical reports and ancillary data. As a result of this analysis, ASIS was positively evaluated to support the FAO early warning system.     

Muscle proton T2 relaxation times and work during repetitive maximal voluntary exercise

We studied the effects of progressive maximal voluntary handgrip contractions (MVCs) on muscle proton spin-spin (T2) relaxation times and work, measured as the integrated force vs. time curve (FTI). Six healthy volunteers performed 10, 20, 40, and 80 MVCs in a 0.35-T magnet on four separate occasions. Repeated measures analyses of variance of increases in T2 and FTI during successive bouts were significant (P < 0.005 and P < 0.001, respectively). FTI increased with successive bouts to a greater extent than did muscle T2 (P < 0.05). For T2, the Helmert contrast judged the 10-MVC response lower than the mean of the remaining responses (P < 0.005), and the differences between all others compared with the means of subsequent responses were not significant, indicating a "flattening" of the T2 response after the increase from 10 to 20 repetitions. For FTI, all the single degree of freedom Helmert contrasts were significant (P < 0.001), indicating a continual increase in response over increased MVCs. The curved nature of the T2 response conformed best to a hyperbolic function, suggesting that a limit of approximately 32% exists for the change in T2 during progressively longer bouts of MVCs. A limit in the T2 response is consistent with the existence of a limit in the amount of water that muscle can take up from the vasculature during exertion.     

Analysis of the Functional Block Involved in the Design of Radial Basis Function Networks

The main architectures, learning abilities and applications of radial basis function (RBF) neural networks are well documented. However, to the best of our knowledge, no in-depth analyses have been carried out into the influence on the behaviour of the neural network arising from the use of different alternatives for the design of an RBF (different non-linear functions, distances, number of neurons, structures, etc.). Thus, as a complement to the existing intuitive knowledge, it is necessary to have a more precise understanding of the significance of the different alternatives. In the present contribution, the relevance and relative importance of the parameters involved in such a design are investigated by using a statistical tool, the ANalysis Of the VAriance (ANOVA). In order to obtain results that are widely applicable, various problems of classification, functional approximation and time series estimation are analyzed. Conclusions are drawn regarding the whole set.     

Risk-benefit analysis for industrial and social needs

This study develops a decision method for evaluating the social acceptability of industrial controls on hazardous materials. Decisions are based on a "multiple criteria approach" that jointly considers measures such as risk-benefit tradeoff, minimum reducible health risk, maximum acceptable cost and implicit value of human life. Health risks are calculated by combining separate estimates of production and usage patterns, emissions to air and water, effectiveness of controls, pollutant dispersion and human susceptibility. Economic benefits consider employment, trade and consumer impacts, as well as direct costs of controls. The analysis focuses on asbestos as an example hazard. Relative values of hazard reduction alternatives are examined for asbestos manufacturing exhaust filters and for asbestos substitutes in brake linings. Preliminary calculations indicate risk reductions of these alternatives cannot justify their social costs.     

Influence of the gasket materials on the clamping pressure distribution in a PEM water electrolyzer: Bolt torques and operation mode in pre-conditioning

To keep optimally connected, all electrolysis cell elements is one of the most important design criteria. The optimal distribution of the clamping points is crucial to increasing cell performance. In this work, the compression pressure distribution inside of a 25 cm² PEM electrolysis cell was evaluated, using different materials: Teflon®, Viton®, ethylene propylene diene monomer rubber (EPDM), and nitrile rubber. Sealing material evaluation was performed taking as performance indicators: total compressed area (%) and compression pressure, for different torques applied. Pressure distribution was obtained by using pressure-sensitive films, analyzing the distribution of pressure points from three-dimensional plots (3D), and quantifying intensities of the images obtained. Results showed that pressure points distribution depends on the stiffness and thickness of the gasket materials. For a tightening torque of 3.70 N m, a pressure of 2.23 MPa is obtained with 85% of the membrane area compressed using nitrile rubber-EPDM gaskets.