Retinoid-Induced Expression and Activity of an Immediate Early Tumor Suppressor Gene in Vascular Smooth Muscle Cells

Retinoids are used clinically to treat a number of hyper-proliferative disorders and have been shown in experimental animals to attenuate vascular occlusive diseases, presumably through nuclear receptors bound to retinoic acid response elements (RARE) located in target genes. Here, we show that natural or synthetic retinoids rapidly induce mRNA and protein expression of a specific isoform of A-Kinase Anchoring Protein 12 (AKAP12β) in cultured smooth muscle cells (SMC) as well as the intact vessel wall. Expression kinetics and actinomycin D studies indicate Akap12β is a retinoid-induced, immediate-early gene. Akap12β promoter analyses reveal a conserved RARE mildly induced with atRA in a region that exhibits hyper-acetylation. Immunofluorescence microscopy and protein kinase A (PKA) regulatory subunit overlay assays in SMC suggest a physical association between AKAP12β and PKA following retinoid treatment. Consistent with its designation as a tumor suppressor, inducible expression of AKAP12β attenuates SMC growth in vitro. Further, immunohistochemistry studies establish marked decreases in AKAP12 expression in experimentally-injured vessels of mice as well as atheromatous lesions in humans. Collectively, these results demonstrate a novel role for retinoids in the induction of an AKAP tumor suppressor that blocks vascular SMC growth thus providing new molecular insight into how retiniods may exert their anti-proliferative effects in the injured vessel wall

Enhanced Thermal Conductivity for LWR Fuel

Summary of Project Status During the program period reported above the computational model was modified to clarify some issues related to the validity of the model. Specific questions being looked at by Dr. Wei Jiang, a post doctoral research associate working part time on this project has been to incorporate the effect of temperature dependent properties. The outcome is a comprehensive study which has been accepted for publication in the Journal of Nuclear Technology. It has been demonstrated that the effective thermal conductivity of this proposed advanced nuclear fuel, a mixture of SiC with enriched UO 2 , is higher than the conventional UO 2 fuel. Predicted maximum temperatures at the center-line of the fuel rods have numerically been shown to be lower than what would be encountered in the conventional fuel rod. The higher thermal conductivity of SiC along with its other prominent reactor-grade properties makes it a potential material to address some of the related issues when used in UO 2 [97% TD]. This ongoing research, in collaboration with the University of Florida, aims to investigate the feasibility and develop a formal methodology of producing the resultant composite oxide fuel. Calculations of effective thermal conductivity of the new fuel as a function of %SiC for certain percentages are presented as a preliminary approach. Heat transfer mechanism in this fuel is explained using a finite volume approach and validated against existing numerical models. FLUENT 6.1.22 was used for thermal conductivity calculations and to estimate reduction in centerline temperatures achievable within such a fuel rod. Later, computer codes COMBINE-PC and VENTURE-PC were deployed to estimate the fuel enrichment required, to maintain the same burnup levels, corresponding to a volume percent addition of SiC. ACOMPLISHMENTS: The result of the research work was published as a MS thesis of one of my students. " Update on the last report: The microstructure of fuel rod is assumed in three geometries: a best case, an average case and a poor case. Thermal conductivity is calculated numerically with the FLUENT under above assumptions. Then the effective thermal conductivity values obtained are used in the FLUENT to calculate temperature profiles considering in-pile conditions. There were some problems reported in the last report, these have now been taken care of. Firstly, the calculation of effective thermal conductivity with the FLUENT is performed under the assumptions that calculating units of all three geometries are independent in the rod and that there is no heat transfer among the units. However, units do not meet the necessary symmetry requirements for the average case and poor case. In addition, the effective thermal conductivity should have been calculated over the entire relevant temperature range, and not only with average values of the thermal conductivity of the constituents. Secondly, it is inadequate to conduct some comparisons with analytical models from the literature, which are not applicable to this material containing more than 90 volume percentage of inclusions. For example, the models of Maxwell, Meredith and Tobias should only be used for low volume fraction of inclusions. Realistically, it is also difficult to have this volume fraction of spheres in the material. To solve the first problem, we remodeled the calculation units of average case and poor case, which were built in symmetry manners in the new models. In an effort to improve the average case, though the coating on UO 2 is still incomplete, the SiC layers cover two opposite faces rather than two adjacent faces against an edge in the original case. The poor case model is remodeled in a manner that SiC layers are separated by UO 2 blocks in the radial direction to satisfy the symmetry requirements. For the calculation in the entire temperature range, we now calculated thermal conductivity at several typical temperature points to satisfy range applicability requirement at reasonable simulation time cost. For the second problem, two new volume percentages below 90%, such as 85% and 89%, were introduced into the simulations. Based on the FLUENT results in the new volume percentages, comparisons weree made with some analytical models from the literature to validate the models. Below we describe the already completed work (complete work) ABSTRACT Thermal conductivity of the fuel in today's Light Water Reactors, Uranium dioxide, can be improved by incorporating a uniformly distributed heat conducting network of a higher conductivity material, Silicon Carbide. The higher thermal conductivity of SiC along with its other prominent reactor-grade properties makes it a potential material to address some of the related issues when used in UO 2 [97% TD]. This ongoing research, in collaboration with the University of Florida, aims to investigate the feasibility and develop a formal methodology of producing the resultant composite oxide fuel. Calculations of effective thermal conductivity of the new fuel as a function of %SiC for certain percentages and as a function of temperature are presented as a preliminary approach. The effective thermal conductivities are obtained at different temperatures from 600K to 1600K. The corresponding polynomial equations for the temperature-dependent thermal conductivities are given based on the simulation results. Heat transfer mechanism in this fuel is explained using a finite volume approach and validated against existing empirical models. FLUENT 6.1.22 was used for thermal conductivity calculations and to estimate reduction in centerline temperatures achievable within such a fuel rod. Later, computer codes COMBINE-PC and VENTURE-PC were deployed to estimate the fuel enrichment required, to maintain the same burnup levels, corresponding to a volume percent addition of SiC

Sequencing of mitochondrial genomes of nine Aspergillus and Penicillium species identifies mobile introns and accessory genes as main sources of genome size variability

BACKGROUND: The genera Aspergillus and Penicillium include some of the most beneficial as well as the most harmful fungal species such as the penicillin-producer Penicillium chrysogenum and the human pathogen Aspergillus fumigatus, respectively. Their mitochondrial genomic sequences may hold vital clues into the mechanisms of their evolution, population genetics, and biology, yet only a handful of these genomes have been fully sequenced and annotated. RESULTS: Here we report the complete sequence and annotation of the mitochondrial genomes of six Aspergillus and three Penicillium species: A. fumigatus, A. clavatus, A. oryzae, A. flavus, Neosartorya fischeri (A. fischerianus), A. terreus, P. chrysogenum, P. marneffei, and Talaromyces stipitatus (P. stipitatum). The accompanying comparative analysis of these and related publicly available mitochondrial genomes reveals wide variation in size (25–36 Kb) among these closely related fungi. The sources of genome expansion include group I introns and accessory genes encoding putative homing endonucleases, DNA and RNA polymerases (presumed to be of plasmid origin) and hypothetical proteins. The two smallest sequenced genomes (A. terreus and P. chrysogenum) do not contain introns in protein-coding genes, whereas the largest genome (T. stipitatus), contains a total of eleven introns. All of the sequenced genomes have a group I intron in the large ribosomal subunit RNA gene, suggesting that this intron is fixed in these species. Subsequent analysis of several A. fumigatus strains showed low intraspecies variation. This study also includes a phylogenetic analysis based on 14 concatenated core mitochondrial proteins. The phylogenetic tree has a different topology from published multilocus trees, highlighting the challenges still facing the Aspergillus systematics. CONCLUSIONS: The study expands the genomic resources available to fungal biologists by providing mitochondrial genomes with consistent annotations for future genetic, evolutionary and population studies. Despite the conservation of the core genes, the mitochondrial genomes of Aspergillus and Penicillium species examined here exhibit significant amount of interspecies variation. Most of this variation can be attributed to accessory genes and mobile introns, presumably acquired by horizontal gene transfer of mitochondrial plasmids and intron homing