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     

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.     

A dual mesh scheme for finite element based reconstruction algorithms

The finite element (FE) method has found several applications in emerging imaging modalities, especially microwave imaging which has been shown to be potentially useful in a number of areas including thermal estimation. In monitoring temperature distributions, the biological phenomena of temperature variations of tissue dielectric properties is exploited. By imaging these properties and their changes during such therapies as hyperthermia, temperature distributions can be deduced using difference imaging techniques. The authors focus on a microwave imaging problem where the hybrid element (HE) method is used in conjunction with a dual mesh scheme in an effort to image complex wavenumbers, k(2). The dual mesh scheme is introduced to improve the reconstructed images of tissue properties and is ideally suited for systems using FE methods as their computational base. Since the electric fields typically vary rapidly over a given body when irradiated by high-frequency electromagnetic sources, a dense mesh is needed for these fields to be accurately represented. Conversely, k(2) may be fairly constant over subregions of the body which would allow for a less dense sampling of this parameter in those regions. In the dual mesh system employed, the first mesh, which is uniformly dense, is used for calculating the electric fields over the body whereas the second mesh, which is nonuniform and less dense, is used for representing the k(2) distribution within the region of interest. The authors examine the 2-D TM polarization case for a pair of dielectric distributions on both a large and small problem to demonstrate the flexibility of the dual mesh method along with some of the difficulties associated with larger imaging problems. Results demonstrate the capabilities of the dual mesh concept in comparison to a single mesh approach for a variety of test cases, suggesting that the dual mesh method is critical for FE based image reconstruction where rapidly varying physical quantities are used to recover smoother property profiles, as can occur in microwave imaging of biological bodies.     

2,4-Diamino-5-(2'-arylpropargyl)pyrimidine derivatives as new nonclassical antifolates for human dihydrofolate reductase inhibition

Dihydrofolate reductase (DHFR) has been a well-recognized target for the development of therapeutics for human cancers for several decades. Classical inhibitors of DHFR use an active transport mechanism to gain access to the cell; disabling this mechanism creates a pathway for resistance. In response, recent research focuses on nonclassical lipid-soluble DHFR inhibitors that are designed to passively diffuse through the membrane. Here, a new series of propargyl-linked antifolates are investigated as potential nonclassical human DHFR inhibitors. Several of these compounds exhibit potent enzyme inhibition with 50% inhibition concentration values under 500 nM. Molecular docking investigations show that the compounds maintain conserved hydrogen bonds between the pyrimidine ring and the enzyme as well as form van der Waals interactions with critical residues in the active site. Interestingly, the most potent compound, 2,4-diamino-5-(3-(3,4,5-trimethoxyphenyl)prop-1-ynyl)-6-ethylpyrimidine (compound 35), is 3500-fold more potent than trimethoprim, a potent inhibitor of bacterial DHFR but weak inhibitor of human DHFR. The two structural differences between compound 35 and trimethoprim show that the propargyl linkage and the substitution at C6 of the pyrimidine ring are critical to the formation of contacts with Thr 56, Ser 59, Ile 60, Leu 22, Phe 31 and Phe 34 and hence, to enhancing potency. The propargyl-linked antifolates are efficient ligands with a high ratio of potency to the number of non-hydrogen atoms and represent a potentially fruitful avenue for future development of antineoplastic agents.     

Retrograde Amnesia in Dementia: Comparison of HIV-Associated Dementia, Alzheimer's Disease, and Huntington's Disease.

Remote memory was assessed in persons with HIV-associated dementia (HIV-D), probable Alzheimer's disease (AD), and Huntington's disease (HD) and in healthy controls. The clinical groups were similar in overall dementia severity. Each clinical group exhibited impairments on remote memory tests relative to controls; however, temporally graded memory loss with selective preservation of older information was observed in the AD group but not the HD or HIV-D group. Analysis of cued retrieval indicated a preferential cuing benefit for the HIV-D and HD groups relative to the AD group. The similar pattern of remote memory performance demonstrated by the HIV-D and HD groups is a novel finding and suggests a subcortically mediated retrograde amnesia in HIV-D. The temporally graded pattern and the abnormal cued retrieval performance in the AD group are consistent with a consolidation deficit associated with extrahippocampal (cortical) and hippocampal damage. (PsycINFO Database Record (c) 2010 APA, all rights reserved)