Nuclear Thermal Rocket Element Environmental Simulator (NTREES) Upgrade Activities

To support the on-going nuclear thermal propulsion effort, a state-of-the-art non nuclear experimental test setup has been constructed to evaluate the performance characteristics of candidate fuel element materials and geometries in representative environments. The facility to perform this testing is referred to as the Nuclear Thermal Rocket Element Environment Simulator (NTREES). This device can simulate the environmental conditions (minus the radiation) to which nuclear rocket fuel components will be subjected during reactor operation. Test articles mounted in the simulator are inductively heated in such a manner so as to accurately reproduce the temperatures and heat fluxes which would normally occur as a result of nuclear fission and would be exposed to flowing hydrogen. Initial testing of a somewhat prototypical fuel element has been successfully performed in NTREES and the facility has now been shutdown to allow for an extensive reconfiguration of the facility which will result in a significant upgrade in its capabilitie

Initial Operation of the Nuclear Thermal Rocket Element Environmental Simulator

The Nuclear Thermal Rocket Element Environmental Simulator (NTREES) facility is designed to perform realistic non-nuclear testing of nuclear thermal rocket (NTR) fuel elements and fuel materials. Although the NTREES facility cannot mimic the neutron and gamma environment of an operating NTR, it can simulate the thermal hydraulic environment within an NTR fuel element to provide critical information on material performance and compatibility. The NTREES facility has recently been upgraded such that the power capabilities of the facility have been increased significantly. At its present 1.2 MW power level, more prototypical fuel element temperatures nay now be reached. The new 1.2 MW induction heater consists of three physical units consisting of a transformer, rectifier, and inverter. This multiunit arrangement facilitated increasing the flexibility of the induction heater by more easily allowing variable frequency operation. Frequency ranges between 20 and 60 kHz can accommodated in the new induction heater allowing more representative power distributions to be generated within the test elements. The water cooling system was also upgraded to so as to be capable of removing 100% of the heat generated during testing In this new higher power configuration, NTREES will be capable of testing fuel elements and fuel materials at near-prototypic power densities. As checkout testing progressed and as higher power levels were achieved, several design deficiencies were discovered and fixed. Most of these design deficiencies were related to stray RF energy causing various components to encounter unexpected heating. Copper shielding around these components largely eliminated these problems. Other problems encountered involved unexpected movement in the coil due to electromagnetic forces and electrical arcing between the coil and a dummy test article. The coil movement and arcing which were encountered during the checkout testing effectively destroyed the induction coil in use at the time and resulted in NTREES being out of commission for a couple of months while a new stronger coil was procured. The new coil includes several additional pieces of support structure to prevent coil movement in the future. In addition, new insulating test article support components have been fabricated to prevent unexpected arcing to the test articles. Additional activities are also now underway to address ways in which the radial temperature profiles across test articles may be controlled such that they are more prototypical of what they would encounter in an operating nuclear engine. The causes of the temperature distribution problem are twofold. First, the fuel element test article is isolated in NTREES as opposed to being in the midst of many other mostly identical fuel elements in a nuclear engine. As a result, the fuel element heat flux boundary conditions in NTREES are far from adiabatic as would normally be the case in a reactor. Second, induction heating skews the power distribution such that power is preferentially deposited near the outside of the fuel element. Nuclear heating, conversely, deposits its power much more uniformly throughout the fuel element. Current studies are now looking at various schemes to adjust the amount of thermal radiation emitted from the fuel element surface so as to essentially vary the thermal boundary conditions on the test article. It is hoped that by properly adjusting the thermal boundary conditions on the fuel element test article, it may be possible to substantially correct for the inappropriate radial power distributions resulting from the induction heating so as to yield a more nearly correct temperature distribution throughout the fuel element

Performance of an Annular Linear Induction Pump with Applications to Space Nuclear Power Systems

Results of performance testing of an annular linear induction pump are presented. The pump electromagnetically pumps liquid metal through a circuit specially designed to allow for quantification of the performance. Testing was conducted over a range of conditions, including frequencies of 33, 36, 39, and 60 Hz, liquid metal temperatures from 125 to 525 C, and input voltages from 5 to 120 V. Pump performance spanned a range of flow rates from roughly 0.16 to 5.7 L/s (2.5 to 90 gpm), and pressure head less than 1 to 90 kPa (less than 0.145 to 13 psi). The maximum efficiency measured during testing was slightly greater than 6%. The efficiency was fairly insensitive to input frequency from 33 to 39 Hz, and was markedly lower at 60 Hz. In addition, the efficiency decreased as the NaK temperature was raised. The performance of the pump operating on a variable frequency drive providing 60 Hz power compared favorably with the same pump operating on 60 Hz power drawn directly from the electrical grid

Pleosporales

One hundred and five generic types of Pleosporales are described and illustrated. A brief introduction and detailed history with short notes on morphology, molecular phylogeny as well as a general conclusion of each genus are provided. For those genera where the type or a representative specimen is unavailable, a brief note is given. Altogether 174 genera of Pleosporales are treated. Phaeotrichaceae as well as Kriegeriella, Zeuctomorpha and Muroia are excluded from Pleosporales. Based on the multigene phylogenetic analysis, the suborder Massarineae is emended to accommodate five families, viz. Lentitheciaceae, Massarinaceae, Montagnulaceae, Morosphaeriaceae and Trematosphaeriaceae

Functional Dichotomy between NKG2D and CD28-Mediated Co-Stimulation in Human CD8+ T Cells

Both CD28 and NKG2D can function as co-stimulatory receptors in human CD8+ T cells. However, their independent functional contributions in distinct CD8+ T cell subsets are not well understood. In this study, CD8+ T cells in human peripheral blood- and lung-derived lymphocytes were analyzed for CD28 and NKG2D expression and function. We found a higher level of CD28 expression in PBMC-derived naïve (CD45RA+CD27+) and memory (CD45RA−CD27+) CD8+ T cells (CD28Hi), while its expression was significantly lower in effector (CD45RA+CD27−) CD8+ T cells (CD28Lo). Irrespective of the differences in the CD28 levels, NKG2D expression was comparable in all three CD8+ T cell subsets. CD28 and NKG2D expressions followed similar patterns in human lung-resident GILGFVFTL/HLA-A2-pentamer positive CD8+ T cells. Co-stimulation of CD28Lo effector T cells via NKG2D significantly increased IFN-γ and TNF-α levels. On the contrary, irrespective of its comparable levels, NKG2D-mediated co-stimulation failed to augment IFN-γ and TNF-α production in CD28Hi naïve/memory T cells. Additionally, CD28-mediated co-stimulation was obligatory for IL-2 generation and thereby its production was limited only to the CD28Hi naïve/memory subsets. MICA, a ligand for NKG2D was abundantly expressed in the tracheal epithelial cells, validating the use of NKG2D as the major co-stimulatory receptor by tissue-resident CD8+ effector T cells. Based on these findings, we conclude that NKG2D may provide an expanded level of co-stimulation to tissue-residing effector CD8+ T cells. Thus, incorporation of co-stimulation via NKG2D in addition to CD28 is essential to activate tumor or tissue-infiltrating effector CD8+ T cells. However, boosting a recall immune response via memory CD8+ T cells or vaccination to stimulate naïve CD8+ T cells would require CD28-mediated co-stimulation

cIAP-1 Controls Innate Immunity to C. pneumoniae Pulmonary Infection

The resistance of epithelial cells infected with Chlamydophila pneumoniae for apoptosis has been attributed to the induced expression and increased stability of anti-apoptotic proteins called inhibitor of apoptosis proteins (IAPs). The significance of cellular inhibitor of apoptosis protein-1 (cIAP-1) in C. pneumoniae pulmonary infection and innate immune response was investigated in cIAP-1 knockout (KO) mice using a novel non-invasive intra-tracheal infection method. In contrast to wildtype, cIAP-1 knockout mice failed to clear the infection from their lungs. Wildtype mice responded to infection with a strong inflammatory response in the lung. In contrast, the recruitment of macrophages was reduced in cIAP-1 KO mice compared to wildtype mice. The concentration of Interferon gamma (IFN-γ) was increased whereas that of Tumor Necrosis Factor (TNF-α) was reduced in the lungs of infected cIAP-1 KO mice compared to infected wildtype mice. Ex vivo experiments on mouse peritoneal macrophages and splenocytes revealed that cIAP-1 is required for innate immune responses of these cells. Our findings thus suggest a new immunoregulatory role of cIAP-1 in the course of bacterial infection

The histone deacetylase inhibitor Trichostatin A modulates CD4+ T cell responses

BACKGROUND: Histone deacetylase inhibitors (HDACIs) induce hyperacetylation of core histones modulating chromatin structure and affecting gene expression. These compounds are also able to induce growth arrest, cell differentiation, and apoptotic cell death of tumor cells in vitro as well as in vivo. Even though several genes modulated by HDAC inhibition have been identified, those genes clearly responsible for the biological effects of these drugs have remained elusive. We investigated the pharmacological effect of the HDACI and potential anti-cancer agent Trichostatin A (TSA) on primary T cells. METHODS: To ascertain the effect of TSA on resting and activated T cells we used a model system where an enriched cell population consisting of primary T-cells was stimulated in vitro with immobilized anti-CD3/anti-CD28 antibodies whilst exposed to pharmacological concentrations of Trichostatin A. RESULTS: We found that this drug causes a rapid decline in cytokine expression, accumulation of cells in the G(1 )phase of the cell cycle, and induces apoptotic cell death. The mitochondrial respiratory chain (MRC) plays a critical role in the apoptotic response to TSA, as dissipation of mitochondrial membrane potential and reactive oxygen species (ROS) scavengers block TSA-induced T-cell death. Treatment of T cells with TSA results in the altered expression of a subset of genes involved in T cell responses, as assessed by microarray gene expression profiling. We also observed up- as well as down-regulation of various costimulatory/adhesion molecules, such as CD28 and CD154, important for T-cell function. CONCLUSIONS: Taken together, our findings indicate that HDAC inhibitors have an immunomodulatory potential that may contribute to the potency and specificity of these antineoplastic compounds and might be useful in the treatment of autoimmune disorders

Genome Wide DNA Copy Number Analysis of Serous Type Ovarian Carcinomas Identifies Genetic Markers Predictive of Clinical Outcome

Ovarian cancer is the fifth leading cause of cancer death in women. Ovarian cancers display a high degree of complex genetic alterations involving many oncogenes and tumor suppressor genes. Analysis of the association between genetic alterations and clinical endpoints such as survival will lead to improved patient management via genetic stratification of patients into clinically relevant subgroups. In this study, we aim to define subgroups of high-grade serous ovarian carcinomas that differ with respect to prognosis and overall survival. Genome-wide DNA copy number alterations (CNAs) were measured in 72 clinically annotated, high-grade serous tumors using high-resolution oligonucleotide arrays. Two clinically annotated, independent cohorts were used for validation. Unsupervised hierarchical clustering of copy number data derived from the 72 patient cohort resulted in two clusters with significant difference in progression free survival (PFS) and a marginal difference in overall survival (OS). GISTIC analysis of the two clusters identified altered regions unique to each cluster. Supervised clustering of two independent large cohorts of high-grade serous tumors using the classification scheme derived from the two initial clusters validated our results and identified 8 genomic regions that are distinctly different among the subgroups. These 8 regions map to 8p21.3, 8p23.2, 12p12.1, 17p11.2, 17p12, 19q12, 20q11.21 and 20q13.12; and harbor potential oncogenes and tumor suppressor genes that are likely to be involved in the pathogenesis of ovarian carcinoma. We have identified a set of genetic alterations that could be used for stratification of high-grade serous tumors into clinically relevant treatment subgroups

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field