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.     

Endogenous Neighborhood Selection and the Attainment of Cooperation in a Spatial Prisoner’s Dilemma Game

There is a large literature in economics and elsewhere on the emergence and evolution of cooperation in the repeated Prisoner’s Dilemma. Recently this literature has expanded to include games in a setting where agents play only with local neighbors in a specified geography. In this paper we explore how the ability of agents to move and choose new locations and new neighbors influences the emergence of cooperation. First, we explore the dynamics of cooperation by investigating agent strategies that yield Markov transition probabilities. We show how different agent strategies yield different Markov chains which generate different asymptotic behaviors in regard to the attainment of cooperation. Second, we investigate how agent movement affects the attainment of cooperation in various networks using agent-based simulations. We show how network structure and density can affect cooperation with and without agent movement.     

EDUCA: A web 2.0 authoring tool for developing adaptive and intelligent tutoring systems using a Kohonen network

This paper presents a Web 2.0 Learning Environment, for a systematic creation of adaptive and intelligent tutoring systems. Authoring contents is made by a community of users including teachers and students. The tutoring systems adapt the contents according to the best learning style using self-organizing maps (SOMs). The SOM was trained for classifying Felder–Silverman learning styles. The most important advantage of these unsupervised neural networks is that they do not require an external teacher for presenting a training set. The approach was implemented under an authoring tool that allows the production of personalized learning material to be used under collaborative and mobile learning environments. The tutoring systems together with the neural network can also be exported to mobile devices. We present different results to the approach working under the authoring tool.     

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.     

Design study of a 120-keV,3He neutral beam injector

We describe a design for a 120-keV, 2.3-MW,³He neutral beam injector for use on a D-³He fusion reactor. The constraint that limits operating life when injecting He is its high sputtering rate. The sputtering is partly controlled by using an extra grid to prevent ion flow from the neutralizer duct to the electron suppressor grid, but a tradeoff between beam current and operating life is still required. Hollow grid wires functioning as mercury heat pipes cool the grid and enable steady state operation. Voltage holding and radiation effects on the acceleration grid structure are discussed. We also briefly describe the vacuum system and analyze use of a direct energy converter to recapture energy from unneutralized ions exiting the neutralizer. Of crucial importance to the technical feasibility of the³He-burning reactor are the injector efficiency and cost; these are 53% and $5.5 million, respectively, when power supplies are included.The beam is composed of 91 separate, parallel currents that flow in the gaps between the elements or wires of a grid. Each such flow is referred to as a beamlet. The current densities in Figs. 5, 8, and 9 are values within a beamlet, as measured at the beam-forming grid. They are not values averaged over the entire beam cross-section.     

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.     

Urbanisation and Shallow Groundwater: Predicting Changes in Catchment Hydrological Responses

The impact of urbanisation on catchment hydrological response was investigated by using a process-based coupled surface water–groundwater model (MODHMS). The modelling estimated likely changes in river discharge as a result of land-use change in the Southern River catchment in Western Australia, underlined by a highly transmissive aquifer, has permeable soils and a shallow watertable. A significant increase in total annual discharge was predicted as a result of urbanisation area with the runoff coefficient rising from 0.01 to more than 0.40. In contrast with urban areas elsewhere, these changes were mainly due to a shift in the subsurface water balance, leading to significant reduction in evaporative losses from the soil profile and shallow watertable after urbanisation (from nearly 80 % of infiltration to less than 20 %). The infiltration of roof and road runoff and establishment of subsurface drainage adopted in local construction practice leads to higher groundwater recharge rates and subsequently groundwater discharge to the urban drainage network. Urban density and groundwater abstraction for urban irrigation most strongly influence the urbanisation impact on catchment fluxes. The results shows that urban development leads to a production of ‘harvestable’ water; and depending on local needs, this water could be used for public and private water supply or to improve environmental flows.