Compartmentalization of Cells Bearing "Rheumatic” Cell Surface Antigens in Peripheral Blood and Tonsils in Rheumatic Heart Disease

Monoclonal antibodies that recognize "rheumatic” antigens of peripheral blood non-T cells were used to study the compartmentalization of such cells in peripheral blood and tonsils of individuals with rheumatic heart disease (RHD) and suitable control subjects. The peripheral blood of most (71%) of the 42 individuals with RHD contained cells reacting with monoclonal antibody 83S19.23 or 256S.10, whereas these cells were present in only 17% of the 41 control subjects (P < .02). However, none of 21 individuals with RHD had such cells in their tonsils, although they were present in the tonsils of 50% of the 40 control subjects (P < .03). These results may reflect a failure in RHD of organ-specific homing of cells with the epitopes recognized by the antibodies. The presence of these cells in tonsils may be important in the immune response to streptococcal pharyngeal infection, and their absence in RHD may be involved in the unusual immune responses characteristic of this diseas

Detection of Shielded Nuclear Material in a Cargo Container

The Idaho National Laboratory, along with Los Alamos National Laboratory and the Idaho State University’s Idaho Accelerator Center, are developing electron accelerator-based, photonuclear inspection technologies for the detection of shielded nuclear material within air-, rail-, and especially, maritime-cargo transportation containers. This paper describes a developing prototypical cargo container inspection system utilizing the Pulsed Photonuclear Assessment (PPA) technology, incorporates interchangeable, well-defined, contraband shielding structures (i.e., "calibration" pallets) providing realistic detection data for induced radiation signatures from smuggled nuclear material, and provides various shielded nuclear material detection results. Using a 4.8-kg quantity of depleted uranium, neutron and gamma-ray detection responses are presented for well-defined shielded and unshielded configurations evaluated in a selected cargo container inspection configuration. © 2001 Elsevier Science. All rights reserve

Pulsed Photonuclear Assessment (PPA) Technique: CY 04 Year-end Progress Report

Idaho National Laboratory (INL), along with Los Alamos National Laboratory (LANL) and Idaho State University’s Idaho Accelerator Center (IAC), are developing an electron accelerator-based, photonuclear inspection technology for the detection of smuggled nuclear material within air-, rail-, and especially, maritime-cargo transportation containers. This CY04 report describes the latest developments and progress with the development of the Pulsed, Photonuclear Assessment (PPA) nuclear material inspection ystem, such as: (1) the identification of an optimal range of electron beam energies for interrogation applications, (2) the development of a new “cabinet safe” electron accelerator (i.e., Varitron II) to assess “cabinet safe-type” operations, (3) the numerical and experimental validation responses of nuclear materials placed within selected cargo configurations, 4) the fabrication and utilization of Calibration Pallets for inspection technology performance verification, 5) the initial technology integration of basic radiographic “imaging/mapping” with induced neutron and gamma-ray detection, 6) the characterization of electron beam-generated photon sources for optimal performance, 7) the development of experimentallydetermined Receiver-Operator-Characterization curves, and 8) several other system component assessments. This project is supported by the Department of Homeland Security and is a technology component of the Science & Technology Active Interrogation Portfolio entitled “Photofission-based Nuclear Material Detection and Characterization.

Pulsed Photonuclear Assessment (PPA) Technique: CY-05 Project Summary Report

Idaho National Laboratory, along with Idaho State University’s Idaho Accelerator Center and Los Alamos National Laboratory, is developing an electron accelerator-based, photonuclear inspection technology, called the Pulsed Photonuclear Assessment (PPA) system, for the detection of nuclear material concealed within air-, rail-, and, primarily, maritime-cargo transportation containers. This report summarizes the advances and progress of the system’s development in 2005. The contents of this report include an overview of the prototype inspection system, selected Receiver-Operator-Characteristic curves for system detection performance characterization, a description of the approach used to integrate the three major detection components of the PPA inspection system, highlights of the gray-scale density mapping technique being used for significant shield material detection, and higher electron beam energy detection results to support an evaluation for an optimal interrogating beam energy. This project is supported by the Department of Homeland Security Office of Research and Development and, more recently, the Domestic Nuclear Detection Office

The Complete Genome Sequence of Thermoproteus tenax: A Physiologically Versatile Member of the Crenarchaeota

Here, we report on the complete genome sequence of the hyperthermophilic Crenarchaeum Thermoproteus tenax (strain Kra 1, DSM 2078(T)) a type strain of the crenarchaeotal order Thermoproteales. Its circular 1.84-megabase genome harbors no extrachromosomal elements and 2,051 open reading frames are identified, covering 90.6% of the complete sequence, which represents a high coding density. Derived from the gene content, T. tenax is a representative member of the Crenarchaeota. The organism is strictly anaerobic and sulfur-dependent with optimal growth at 86 degrees C and pH 5.6. One particular feature is the great metabolic versatility, which is not accompanied by a distinct increase of genome size or information density as compared to other Crenarchaeota. T. tenax is able to grow chemolithoautotrophically (CO2/H-2) as well as chemoorganoheterotrophically in presence of various organic substrates. All pathways for synthesizing the 20 proteinogenic amino acids are present. In addition, two presumably complete gene sets for NADH:quinone oxidoreductase (complex I) were identified in the genome and there is evidence that either NADH or reduced ferredoxin might serve as electron donor. Beside the typical archaeal A(0)A(1)-ATP synthase, a membrane-bound pyrophosphatase is found, which might contribute to energy conservation. Surprisingly, all genes required for dissimilatory sulfate reduction are present, which is confirmed by growth experiments. Mentionable is furthermore, the presence of two proteins (ParA family ATPase, actin-like protein) that might be involved in cell division in Thermoproteales, where the ESCRT system is absent, and of genes involved in genetic competence (DprA, ComF) that is so far unique within Archaea

Promoter polymorphism of the erythropoietin gene in severe diabetic eye and kidney complications

Significant morbidity and mortality among patients with diabetes mellitus result largely from a greatly increased incidence of microvascular complications. Proliferative diabetic retinopathy (PDR) and end stage renal disease (ESRD) are two of the most common and severe microvascular complications of diabetes. A high concordance exists in the development of PDR and ESRD in diabetic patients, as well as strong familial aggregation of these complications, suggesting a common underlying genetic mechanism. However, the precise gene(s) and genetic variant(s) involved remain largely unknown. Erythropoietin (EPO) is a potent angiogenic factor observed in the diabetic human and mouse eye. By a combination of case–control association and functional studies, we demonstrate that the T allele of SNP rs1617640 in the promoter of the EPO gene is significantly associated with PDR and ESRD in three European-American cohorts [Utah: P = 1.91 × 10−3; Genetics of Kidneys in Diabetes (GoKinD) Study: P = 2.66 × 10−8; and Boston: P = 2.1 × 10−2]. The EPO concentration in human vitreous body was 7.5-fold higher in normal subjects with the TT risk genotype than in those with the GG genotype. Computational analysis suggests that the risk allele (T) of rs1617640 creates a matrix match with the EVI1/MEL1 or AP1 binding site, accounting for an observed 25-fold enhancement of luciferase reporter expression as compared with the G allele. These results suggest that rs1617640 in the EPO promoter is significantly associated with PDR and ESRD. This study identifies a disease risk-associated gene and potential pathway mediating severe diabetic microvascular complications

Streptococcus iniae M-Like Protein Contributes to Virulence in Fish and Is a Target for Live Attenuated Vaccine Development

Streptococcus iniae is a significant pathogen in finfish aquaculture, though knowledge of virulence determinants is lacking. Through pyrosequencing of the S. iniae genome we have identified two gene homologues to classical surface-anchored streptococcal virulence factors: M-like protein (simA) and C5a peptidase (scpI).S. iniae possesses a Mga-like locus containing simA and a divergently transcribed putative mga-like regulatory gene, mgx. In contrast to the Mga locus of group A Streptococcus (GAS, S. pyogenes), scpI is located distally in the chromosome. Comparative sequence analysis of the Mgx locus revealed only one significant variant, a strain with an insertion frameshift mutation in simA and a deletion mutation in a region downstream of mgx, generating an ORF which may encode a second putative mga-like gene, mgx2. Allelic exchange mutagenesis of simA and scpI was employed to investigate the potential role of these genes in S. iniae virulence. Our hybrid striped bass (HSB) and zebrafish models of infection revealed that M-like protein contributes significantly to S. iniae pathogenesis whereas C5a peptidase-like protein does not. Further, in vitro cell-based analyses indicate that SiMA, like other M family proteins, contributes to cellular adherence and invasion and provides resistance to phagocytic killing. Attenuation in our virulence models was also observed in the S. iniae isolate possessing a natural simA mutation. Vaccination of HSB with the Delta simA mutant provided 100% protection against subsequent challenge with a lethal dose of wild-type (WT) S. iniae after 1,400 degree days, and shows promise as a target for live attenuated vaccine development.Analysis of M-like protein and C5a peptidase through allelic replacement revealed that M-like protein plays a significant role in S. iniae virulence, and the Mga-like locus, which may regulate expression of this gene, has an unusual arrangement. The M-like protein mutant created in this research holds promise as live-attenuated vaccine

Genetic Basis of Myocarditis: Myth or Reality?

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