| 1. |
- van der Brug, MP, et al.
(författare)
-
RNA binding activity of the recessive parkinsonism protein DJ-1 supports involvement in multiple cellular pathways
- 2008
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 105:29, s. 10244-10249
-
Tidskriftsartikel (refereegranskat)abstract
- Parkinson's disease (PD) is a major neurodegenerative condition with several rare Mendelian forms. Oxidative stress and mitochondrial function have been implicated in the pathogenesis of PD but the molecular mechanisms involved in the degeneration of neurons remain unclear. DJ-1 mutations are one cause of recessive parkinsonism, but this gene is also reported to be involved in cancer by promoting Ras signaling and suppressing PTEN-induced apoptosis. The specific function of DJ-1 is unknown, although it is responsive to oxidative stress and may play a role in the maintenance of mitochondria. Here, we show, using four independent methods, that DJ-1 associates with RNA targets in cells and the brain, including mitochondrial genes, genes involved in glutathione metabolism, and members of the PTEN/PI3K cascade. Pathogenic recessive mutants are deficient in this activity. We show that DJ-1 is sufficient for RNA binding at nanomolar concentrations. Further, we show that DJ-1 binds RNA but dissociates after oxidative stress. These data implicate a single mechanism for the pleiotropic effects of DJ-1 in different model systems, namely that the protein binds multiple RNA targets in an oxidation-dependent manner.
|
|
| 2. |
- Arul, A.J, et al.
(författare)
-
Reliability analysis of safety grade decay heat removal system of Indian prototype fast breeder reactor
- 2006
-
Ingår i: Annals of Nuclear Energy. - : Elsevier BV. - 0306-4549. ; 33:2, s. 180-188
-
Tidskriftsartikel (refereegranskat)abstract
- The 500MW Indian pool type Prototype Fast Breeder Reactor (PFBR), is provided with two independent and diverse Decay Heat Removal (DHR) systems viz., Operating Grade Decay Heat Removal System (OGDHRS) and Safety Grade Decay Heat Removal System (SGDHRS). OGDHRS utilizes the secondary sodium loops and Steam–Water System with special decay heat removal condensers for DHR function. The unreliability of this system is of the order of 0.1–0.01. The safety requirements of the present generation of fast reactors are very high, and specifically for DHR function the failure frequency should be less than 1E-7/ry. Therefore, a passive SGDHR system using four completely independent thermo-siphon loops in natural convection mode is provided to ensure adequate core cooling for all Design Basis Events. The very high reliability requirement for DHR function is achieved mainly with the help of SGDHRS. This paper presents the reliability analysis of SGDHR system. Analysis is performed by Fault Tree method using "CRAFT" software developed at Indira Gandhi Centre for Atomic Research. This software has special features for compact representation and CCF analysis of high redundancy safety systems encountered in nuclear reactors. Common Cause Failures (CCF) are evaluated by beta-factor method. The reliability target for SGDHRS arrived from DHR reliability requirement and the ultimate number of demands per year (7/y) on SGDHRS is that the failure frequency should be <=1.4E-8/de. Since it is found from the analysis that the unreliability of SGDHRS with identical loops is 5.2E-6/de and dominated by leak rates of components like AHX, DHX and sodium dump and isolation valves, options with diversity measures in important components were studied. The failure probability of SGDHRS for a design consisting of 2 types of diverse loops (Diverse AHX, DHX and sodium dump and isolation valves) is 2.1E-8/de, which practically meets the reliability requirement.
|
|
| 3. |
- Mathews, T.S, et al.
(författare)
-
Functional reliability analysis of Safety Grade Decay Heat Removal System of Indian 500 MWe PFBR
- 2008
-
Ingår i: Nuclear Engineering and Design. - : Elsevier BV. - 0029-5493 .- 1872-759X. ; 238:9, s. 2369-2376
-
Tidskriftsartikel (refereegranskat)abstract
- Passive systems are increasingly deployed in nuclear industry with an objective of increasing reliability and safety of operations with reduced cost. Methods for assessing the reliability of thermal-hydraulic passive systems, that is systems with moving working fluid, address the issues in natural buoyancy-driven flow that could result in a failure to meet the design safety limits under accident scenarios. This is referred as design functional reliability. This paper presents the results of functional reliability analysis carried out for the passive Safety Grade Decay Heat Removal System (SGDHRS) of IndianPrototype Fast Breeder Reactor (PFBR). The analysis is carried out based on the overall approach reported in the Reliability Methods for Passive System (RMPS, European Commission) project. Functionalfailure probability is calculated using Monte-Carlo method and also with method of moments.
|
|
