CTLA4 mediates antigen-specific apoptosis of human T cells

The regulation of T cell-mediated immune responses requires a balance between amplification and generation of effector function and subsequent selective termination by clonal deletion. Although apoptosis of previously activated T cells can be induced by signaling of the tumor necrosis factor receptor family, these molecules do not appear to regulate T-cell clonal deletion in an antigen-specific fashion. We demonstrate that cross-linking of the inducible T-cell surface molecule CTLA4 can mediate apoptosis of previously activated human T lymphocytes. This function appears to be antigen-restricted, since a concomitant signal T-cell receptor signal is required. Regulation of this pathway may provide a novel therapeutic strategy to delete antigen-specific activated T cells.     

The role of oncostatin M in animal and human connective tissue collagen turnover and its localization within the rheumatoid joint

OBJECTIVE: To study the interaction of interleukin-1alpha (IL-1alpha) and oncostatin M (OSM) in promoting cartilage collagen destruction. METHODS: Bovine, porcine, and human cartilage and human chondrocytes were studied in culture. The levels of collagenase (matrix metalloproteinase 1 [MMP-1]) and tissue inhibitor of metalloproteinases 1 (TIMP-1) were measured by bioassay and enzyme-linked immunosorbent assay (ELISA). The levels of OSM in rheumatoid synovial fluid were measured by ELISA. RESULTS: When combined with OSM, IL-1alpha, IL-1beta, and tumor necrosis factor alpha released proteoglycan and collagen from cartilage. OSM was the only member of the IL-6 family to have this effect. Human tendon also responded to IL-1alpha and OSM. OSM increased the production of MMP-1 and TIMP-1 but when combined with IL-1alpha, synergistically promoted MMP-1 production in human chondrocytes and synovial fibroblasts. High levels of OSM were found in human rheumatoid synovial fluids, and confocal microscopy showed that OSM was produced by macrophages in rheumatoid synovial tissue. CONCLUSION: These results highlight an important new mechanism by which there is irreversible loss of collagen from cartilage.     

Gas chromatography in express diagnosis of candidiasis and monitoring of antifungal therapy efficacy by D-arabinitol and mannose levels in pediatric patients]

Methods for preventing and treating Ebola virus hemorrhagic fever are not still available despite the fact that this virus have been studied for 20 years. Methods of immunization of the animals (sheep, goats) non-susceptible to Ebola virus with live virus preparations were developed to obtain the hyperimmune anti-Ebola virus sera required to have highly immune antivirus gamma-globulins. These methods made it possible to obtain the immune sera having high virus-neutralizing antibodies. Caprine immunoglobulins were obtained from sera by fractionation of immune sera by Kohn's method. The neutralization indices of the immunoglobulins obtained were at least Ig. When administered in the first hours of infection, the protective effect of these preparations was shown on guinea pigs infected with LD50 of the strain pathogenic to the animals. Preclinical trials of these immunoglobulins on laboratory animals and clinical trials on volunteers were performed. The preparation was used as a preventive agent when accidents took place at the laboratory working with Ebola virus. The similar preparation from equine sera having high neutralizing and protective properties was elaborated at the Virological Center, Microbiological Institute, Russian Ministry of Defense. Its prophylactic efficiency was also shown in infected gamadrias.     

Expansion and length-dependent fragility of CTG repeats in yeast

Expansion of DNA trinucleotide repeats (TNRs) is the causative mutation in a growing number of human genetic diseases. Large expansions of a CTG tract were obtained and shown by genetic and physical assays to be length-dependent sites of chromosome breakage in Saccharomyces cerevisiae. Deletion of RAD27, which encodes a nuclease involved in Okazaki fragment processing, caused length-dependent destabilization of CTG tracts and a substantial increase in expansion frequency. The genetic assay described here can be used to evaluate other factors that induce TNR expansion or chromosome fragility in humans.     

Hyperbaric oxygenation and current methods of detoxication in multimodal intensive therapy of diffuse peritonitis

The course of diffuse peritonitis has been followed up in 219 patients, 20 of these with the reactive, 165 with toxic, and 34 with the terminal stages of the condition. Multiple-modality intensive care included, besides routine therapy, local abdominal hypothermia, UV irradiation of autoblood (UVIAB), and, if indicated, hyperbaric oxygenation (HBO) and hemoperfusion. In addition to clinical tests, immunobiochemical monitoring of medium-molecular peptide fractions MM1 and MM2 and index of their distribution, as well as of circulating immune complexes CIC1 and CIC2 and the levels of immunoglobulins IgA, IgM, and IgG were the criteria for assessing the severity of intoxication and efficacy of intensive care and for predicting the course and outcome of the disease. The results indicate that HBO in combination with hemoperfusion, local abdominal hypothermia, and UVIAB have a positive impact on the clinical picture of the disease and on the time course of markers of endogenous intoxication and humoral immunity in patients with the terminal and toxic phases of diffuse peritonitis.     

A review on improving the autonomy of unmanned surface vehicles through intelligent collision avoidance manoeuvres

In recent years unmanned vehicles have grown in popularity, with an ever increasing number of applications in industry, the military and research within air, ground and marine domains. In particular, the challenges posed by unmanned marine vehicles in order to increase the level of autonomy include automatic obstacle avoidance and conformance with the Rules of the Road when navigating in the presence of other maritime traffic. The USV Master Plan which has been established for the US Navy outlines a list of objectives for improving autonomy in order to increase mission diversity and reduce the amount of supervisory intervention. This paper addresses the specific development needs based on notable research carried out to date, primarily with regard to navigation, guidance, control and motion planning. The integration of the International Regulations for Avoiding Collisions at Sea within the obstacle avoidance protocols seeks to prevent maritime accidents attributed to human error. The addition of these critical safety measures may be key to a future growth in demand for USVs, as they serve to pave the way for establishing legal policies for unmanned vessels.     

Posterior representation with a multi‐modal likelihood using the gaussian sum filter for localization in a known map

A Gaussian sum filter (GSF) with component extended Kalman filters (EKF) is proposed as an approach to localizing an autonomous vehicle in an urban environment with limited GPS availability. The GSF uses vehicle‐relative vision‐based measurements of known map features coupled with inertial navigation solutions to accomplish localization in the absence of GPS. The vision‐based measurements have multimodal measurement likelihood functions that are well represented as weighted sums of Gaussian densities. The GSF is used because of its ability to represent the posterior distribution of the vehicle pose with better efficiency (fewer terms, less computational complexity) than a corresponding bootstrap particle filter with various numbers of particles because of the interaction with measurement hypothesis tests. The expectation‐maximization algorithm is used off line to determine the representational efficiency of the particle filter in terms of an effective number of Gaussian densities. In comparison, the GSF, which uses an iterative condensation procedure after each iteration of the filter to maintain real‐time capabilities, is shown through a series of in‐depth empirical studies to more accurately maintain a representation of the posterior distribution than the particle filter using 37 min of recorded data from Cornell University's autonomous vehicle driven in an urban environment, including a 32 min GPS blackout. © 2012 Wiley Periodicals, Inc.