Evaluating the Sensitivity of Mycobacterium tuberculosis to Biotin Deprivation Using Regulated Gene Expression

In the search for new drug targets, we evaluated the biotin synthetic pathway of Mycobacterium tuberculosis (Mtb) and constructed an Mtb mutant lacking the biotin biosynthetic enzyme 7,8-diaminopelargonic acid synthase, BioA. In biotin-free synthetic media, ΔbioA did not produce wild-type levels of biotinylated proteins, and therefore did not grow and lost viability. ΔbioA was also unable to establish infection in mice. Conditionally-regulated knockdown strains of Mtb similarly exhibited impaired bacterial growth and viability in vitro and in mice, irrespective of the timing of transcriptional silencing. Biochemical studies further showed that BioA activity has to be reduced by approximately 99% to prevent growth. These studies thus establish that de novo biotin synthesis is essential for Mtb to establish and maintain a chronic infection in a murine model of TB. Moreover, these studies provide an experimental strategy to systematically rank the in vivo value of potential drug targets in Mtb and other pathogens

DEVELOPMENT OF A SUPERCRITICAL CO2 BRAYTON ENERGY CONVERSION SYSTEM COUPLED WITH A SODIUM COOLED FAST REACTOR

Systematic research has been conducted by KAERI to develop a supercritical carbon dioxide Brayton cycle energy conversion system coupled with a sodium cooled fast reactor. For the development of the supercritical CO2 Brayton cycle ECS, KAERI researched four major fields, separately. For the system development, computer codes were developed to design and analyze the supercritical CO2 Brayton cycle ECS coupled with the KALIMER-600. Computer codes were developed to design and analyze the performance of the major components such as the turbomachinery and the high compactness PCHE heat exchanger. Three dimensional flow analysis was conducted to evaluate their performance. A new configuration for a PCHE heat exchanger was developed by using flow analysis, which showed a very small pressure loss compared with a previous PCHE while maintaining its heat transfer rate. Transient characteristics for the supercritical CO2 Brayton cycle coupled with KALIMER-600 were also analyzed using the developed computer codes. A Na-CO2 pressure boundary failure accident was analyzed with a computer code that included a developed model For the Na-CO2 chemical reaction phenomena. The MMS-LMR code was developed to analyze the system transient and control logic. Oil the basis of the code, the system behavior was analyzed when a turbine load was changed. This paper contains the current research overview of the supercritical CO2 Brayton cycle coupled to the KALIMER-600 as an alternative energy conversion system.X1136sciescopuskc

Constrained Path Monte Carlo for Fermions

In these lectures we describe the constrained path Monte Carlo (CPMC