Segregation of germ granules in living Caenorhabditis elegans embryos: cell-type-specific mechanisms for cytoplasmic localisation

Extrinsic allergic alveolitis and pulmonary sarcoidosis are granulomatous diseases of the lung for which clinical presentation and anatomic site of granuloma formation differ. Extrinsic allergic alveolitis is caused by inhaled antigens, whereas the nature and source of the inciting antigen in sarcoidosis is unknown. To test the hypothesis that the route via which antigen is introduced to the lung contributes to the clinicopathological presentation of pulmonary granulomatous disease, rats immunized with intravenous (i.v.) Corynebacterium parvum were challenged after 2 weeks with either intratracheal (i.t.) or i.v. C. parvum. The granulomatous inflammation elicited by i.t. challenge predominantly involved alveolar spaces and histologically simulated extrinsic allergic alveolitis. In contrast, the inflammation induced by i.v. challenge was characterized by granulomatous angiitis and interstitial inflammation simulating sarcoidosis. Elevations of leukocyte counts and TNF levels in bronchoalveolar fluid, which reflect inflammation in the intra-alveolar compartment, were much more pronounced after i.t. than after i.v. challenge. Tumor necrosis factor, interleukin-6, CC chemokine, CXC chemokine, and adhesion molecule mRNA and protein expression occurred in each model. In conclusion, i.t. or i.v. challenge with C. parvum in sensitized rats caused pulmonary granulomatous inflammation that was histologically similar to human extrinsic allergic alveolitis and sarcoidosis, respectively. Although the soluble and cellular mediators of granulomatous inflammation were qualitatively similar in both disease models, the differing anatomic source of the same antigenic challenge was responsible for differing clinicopathological presentations.     

Evaluation of the recombinant 38-kilodalton antigen of Mycobacterium tuberculosis as a potential immunodiagnostic reagent

The diagnosis of infection caused by Mycobacterium tuberculosis is of increased public health concern following increases in the number of cases in developed countries and major increases in developing countries associated with the spread of human immunodeficiency virus (HIV) infection. The specificity of purified protein derivative skin testing for the detection of infection is compromised by exposure to environmental mycobacteria. Examination of sputum detects the most infectious patients, but not those with extrapulmonary disease. The 38-kDa antigen of M. tuberculosis contains two M. tuberculosis-specific B-cell epitopes. We overexpressed the gene for this antigen in Escherichia coli and evaluated the recombinant product in in vitro assays of T-cell function and as a target for the antibody response in humans. The sensitivity and specificity of the antigen as a skin test reagent were also assessed in outbred guinea pigs. We found that 69% of healthy sensitized humans recognize the antigen in vitro, as manifested by both cell proliferation and the production of gamma interferon. Untreated patients initially have a lower frequency of response (38%); this recovers to 72% during therapy. A total of 292 patients (20 with HIV coinfection) and 58 controls were examined for production of antibody to the 38-kDa antigen by using a commercially available kit. The sensitivity of the test in comparison with that of culture was 72.6%, and the specificity was 94.9%. The antigen was also tested for its ability to induce skin reactions in outbred guinea pigs sensitized by various mycobacterial species. The antigen provoked significant skin reactions in M. tuberculosis-, M. bovis BCG-, and M. intracellulare-sensitized animals. The significance of these findings and the usefulness of this antigen in immunodiagnosis are discussed.     

Theory and application of charge pumping for the characterizationof Si-SiO2 interface and near-interface oxide traps

A generalized charge pumping model has been developed which extends the use of charge pumping from a study of traps at the Si-SiO ₂ interface to a study of traps in the oxide. The analytical model, based on tunneling theory, allows the spatial distribution of near-interface oxide traps to be determined from variable frequency charge pumping data. Profiling of near-interface oxide traps in irradiated MOSFET's as well as SONOS nonvolatile memory devices is presented     

Reperfusion injury delays healing of intestinal anastomosis in a rat

This SAEM position paper clarifies the role of emergency medicine in health care delivery. It builds upon the working definition of emergency medicine developed by the American College of Emergency Physicians in 1994 by describing the health care role of emergency physicians (EPs). EPs are first-contact providers who care for all patients regardless of age, gender, time of presentation, or ability to pay. They remain the only continuously accessible specialty for patients seeking help and solace in the health care system. They are an essential link in the health care continuum between primary care physicians, specialists, the out-of-hospital system, the patient, inpatient services, and communication services. The EP's role is in organizing and monitoring the emergency care delivery system. Part of this role is to better align the health care provider training and ability with the specific medical needs of a patient. The emergency health care system remains the essential medical safety net for all individuals needing care in this country.     

Elimination of vector parasites in finite element Maxwell solutions

The vector parasite problem is studied in the context of finite-element solutions of Maxwell's equations for driven boundary-value problems. An expanded weak form which combines the divergence equation with the conventional weak form of the double-curl equation is introduced. This form is related to penalty methods where the penalty or weighting factor varies with the dielectric constant. The resulting algebraic system is identical to the Galerkin-Helmholtz operator on homogeneous subregions. Normal and tangential boundary conditions arise in terms of the divergence and curl of the field on the boundary which can be reexpressed as equivalent charges and currents. Computational results show the occurrence of two distinct types of parasitic modes in driven problems and their elimination with the formulation presented. Practical observations concerning the conditions which provoke spurious modes in these problems are reported. Spurious solutions arise from improper or unphysical boundary conditions, and the importance of careful specification of boundary-value problems is illustrated. Most conceptual difficulties with boundary conditions per se are removed when hybrid methods are used to couple the interior finite-element solution to the exterior problem. which focuses attention on the physics of the source distribution     

The chlorine/carbon electrode in a silver chloride melt in the temperature range 475–820°C—I: The mechanism and rate of the reaction and the heat of activation

The kinetics of the chlorine evolution on carbon from a silver chloride melt have been studied at several temperatures using the steady state method and galvanostatic methods. Measurements with the double pulse method show that the charge transfer reaction is fast. The Tafel curves indicate that two parallel desorption reactions have about the same rate. The apparent heat of activation have been determined for the various reaction steps.     

Crystal structure of TNF-alpha mutant R31D with greater affinity for receptor R1 compared with R2

Crystal structures have been determined of recombinant human tumor necrosis factor-alpha (TNF-alpha) and its R31D mutant that preferentially binds to TNF receptor R1 with more than seven times the relative affinity of binding to receptor R2. Crystals of the wild-type TNF were of space group P4(1)2(1)2 and had unit cell dimensions of a = b = 94.7 and c = 117.4 A. Refinement of the structure gave an R-factor of 22.3% at 2.5 A resolution. The crystals of TNF R31D mutant diffracted to 2.3 A resolution, and were of identical space group to the wild type with unit cell dimensions of a = b = 95.4 and c = 116.2 A, and the structure was refined to an R-factor of 21.8%. The trimer structures of the wild-type and mutant TNF were similar with a root mean square (r.m.s.) deviation of 0.56 A for Calpha atoms; however, the subunits within each trimer were more variable with an average r.m.s. deviation of 1.00 A on Calpha atoms for pairwise comparison of subunits. Model complexes of TNF with receptors R1 and R2 have been used to predict TNF-receptor interactions. Arg31 in all three subunits of wild-type TNF is predicted to form an ionic interaction with the equivalent glutamic acid in both receptors R1 and R2. Asp31 of the TNF R31D mutant is predicted to interact differently with the two receptors. The side chain of Asp31 in two subunits of the TNF mutant is predicted to form hydrogen bond interactions with Ser59 or Cys70 of R1, while it has no predicted interactions with R2. The loss of three strong ionic interactions of Arg31 and the electrostatic repulsion of Asp31 with Glu in the receptors is consistent with the reduced binding of the R31D mutant to both receptors relative to wild-type TNF. The replacement of these ionic interactions by two weaker hydrogen bond interactions between Asp31 of the R31D mutant and R1, compared with no interactions with R2, is in agreement with the observed preferential binding of the R31D mutant to R1 over R2. Analysis of the structure and function of receptor-discriminating mutants of TNF will help understand the biological role of TNF and facilitate its use as an antitumor agent.      

三大原则激活数据红利

如今,各国政府都在寻找可以通过少量投入实现强大新功能的科技。只要有追求创新的精神和持之以恒的努力,大多数城市都可以实现可持续发展的智能技术解决方案,从而降低成本,提高市政服务水平,改善市民的生活质量。微软委托IDC进行的一项最新研究指出,通过整合零散数据,采用新型数据分析工具,并向更多人传递有用的洞察,全球各国的政府机构在未来四年内从数据挖掘中获得的数据红利将高达2060亿美元,并且越早采用,收益越大。     

如何有效控制存储成本

导读 目前,控制合规成本仍是企业的工作重点之一。其中的难点在于如何在恰当的时间将正确的“内容”保存在适宜的地方。依据传统的做法,企业在对数据归档时只是一味地对数据无限制的存储,无法经济高效地从长远解决数据保留问题。