AFIP-6 Fabrication Summary Report

The AFIP-6 (ATR Full-size plate In center flux trap Position) experiment was designed to evaluate the performance of monolithic fuels at a scale prototypic of research reactor fuel plates. Two qualified fueled plates were fabricated for the AFIP-6 experiment; to be irradiated in the INL Advanced Test Reactor (ATR). This report provides details of the fuel fabrication efforts, including material selection, fabrication processes, and fuel plate qualification

Enhancing the anti-angiogenic action of histone deacetylase inhibitors

<p>Abstract</p> <p>Background</p> <p>Histone deacetylase inhibitors (HDACIs) have many effects on cancer cells, such as growth inhibition, induction of cell death, differentiation, and anti-angiogenesis, all with a wide therapeutic index. However, clinical trials demonstrate that HDACIs are more likely to be effective when used in combination with other anticancer agents. Moreover, the molecular basis for the anti-cancer action of HDACIs is still unknown. In this study, we compared different combinations of HDACIs and anti-cancer agents with anti-angiogenic effects, and analysed their mechanism of action.</p> <p>Results</p> <p>Trichostatin A (TSA) and α-interferon (IFNα) were the most effective combination across a range of different cancer cell lines, while normal non-malignant cells did not respond in the same manner to the combination therapy. There was a close correlation between absence of basal p21^WAF1expression and response to TSA and IFNα treatment. Moreover, inhibition of p21^WAF1expression in a p21^WAF1-expressing breast cancer cell line by a specific siRNA increased the cytotoxic effects of TSA and IFNα. <it>In vitro </it>assays of endothelial cell function showed that TSA and IFNα decreased endothelial cell migration, invasion, and capillary tubule formation, without affecting endothelial cell viability. TSA and IFNα co-operatively inhibited gene expression of some pro-angiogenic factors: vascular endothelial growth factor, hypoxia-inducible factor 1α and matrix metalloproteinase 9, in neuroblastoma cells under hypoxic conditions. Combination TSA and IFNα therapy markedly reduced tumour angiogenesis in neuroblastoma-bearing transgenic mice.</p> <p>Conclusion</p> <p>Our results indicate that combination TSA and IFNα therapy has potent co-operative cytotoxic and anti-angiogenic activity. High basal p21^WAF1expression appears to be acting as a resistance factor to the combination therapy.</p

Withaferin A activates TRIM16 for its anti‐cancer activity in melanoma

Although selective BRAF inhibitors and novel immunotherapies have improved short-term treatment responses in metastatic melanoma patients, acquired resistance to these therapeutics still represent a major challenge in clinical practice. In this study, we evaluated the efficacy of Withaferin A (WFA), derived from the medicinal plant Withania Somnifera, as a novel therapeutic agent for the treatment of melanoma. WFA showed selective toxicity to melanoma cells compared to non-malignant cells. WFA induced apoptosis, significantly reduced cell proliferation and inhibited migration of melanoma cells. We identified that repression of the tumour suppressor TRIM16 diminished WFA cytotoxicity, suggesting that TRIM16 was in part responsible for the cytotoxic effects of WFA in melanoma cells. Together our data indicates that WFA has potent cytopathic effects on melanoma cells through TRIM16, suggesting a potential therapeutic application of WFA in the disease

An examination of the precipitation delivery mechanisms for Dolleman Island, eastern Antarctic Peninsula

Copyright @ 2004 Wiley-BlackwellThe variability of size and source of significant precipitation events were studied at an Antarctic ice core drilling site: Dolleman Island (DI), located on the eastern coast of the Antarctic Peninsula. Significant precipitation events that occur at DI were temporally located in the European Centre for Medium-Range Weather Forecasting (ECMWF) reanalysis data set, ERA-40. The annual and summer precipitation totals from ERA-40 at DI both show significant increases over the reanalysis period. Three-dimensional backwards air parcel trajectories were then run for 5 d using the ECMWF ERA-15 wind fields. Cluster analyses were performed on two sets of these backwards trajectories: all days in the range 1979–1992 (the climatological time-scale) and a subset of days when a significant precipitation event occurred. The principal air mass sources and delivery mechanisms were found to be the Weddell Sea via lee cyclogenesis, the South Atlantic when there was a weak circumpolar trough (CPT) and the South Pacific when the CPT was deep. The occurrence of precipitation bearing air masses arriving via a strong CPT was found to have a significant correlation with the southern annular mode (SAM); however, the arrival of air masses from the same region over the climatological time-scale showed no such correlation. Despite the dominance in both groups of back trajectories of the westerly circulation around Antarctica, some other key patterns were identified. Most notably there was a higher frequency of lee cyclogenesis events in the significant precipitation trajectories compared to the climatological time-scale. There was also a tendency for precipitation trajectories to come from more northerly latitudes, mostly from 50–70°S. The El Niño Southern Oscillation (ENSO) was found to have a strong influence on the mechanism by which the precipitation was delivered; the frequency of occurrence of precipitation from the east (west) of DI increased during El Niño (La Niña) events

Probing for Exoplanets Hiding in Dusty Debris Disks: Disk Imaging, Characterization, and Exploration with HST/STIS Multi-Roll Coronagraphy

Spatially resolved scattered-light images of circumstellar (CS) debris in exoplanetary systems constrain the physical properties and orbits of the dust particles in these systems. They also inform on co-orbiting (but unseen) planets, systemic architectures, and forces perturbing starlight-scattering CS material. Using HST/STIS optical coronagraphy, we have completed the observational phase of a program to study the spatial distribution of dust in ten CS debris systems, and one "mature" protoplanetrary disk all with HST pedigree, using PSF-subtracted multi-roll coronagraphy. These observations probe stellocentric distances > 5 AU for the nearest stars, and simultaneously resolve disk substructures well beyond, corresponding to the giant planet and Kuiper belt regions in our Solar System. They also disclose diffuse very low-surface brightness dust at larger stellocentric distances. We present new results inclusive of fainter disks such as HD92945 confirming, and better revealing, the existence of a narrow inner debris ring within a larger diffuse dust disk. Other disks with ring-like sub-structures, significant asymmetries and complex morphologies include: HD181327 with a posited spray of ejecta from a recent massive collision in an exo-Kuiper belt; HD61005 suggested interacting with the local ISM; HD15115 & HD32297, discussed also in the context of environmental interactions. These disks, and HD15745, suggest debris system evolution cannot be treated in isolation. For AU Mic's edge-on disk, out-of-plane surface brightness asymmetries at > 5 AU may implicate one or more planetary perturbers. Time resolved images of the MP Mus proto-planetary disk provide spatially resolved temporal variability in the disk illumination. These and other new images from our program enable direct inter-comparison of the architectures of these exoplanetary debris systems in the context of our own Solar System.Comment: 109 pages, 43 figures, accepted for publication in the Astronomical Journa

MYCN-targeting miRNAs are predominantly downregulated during MYCN-driven neuroblastoma tumor formation

MYCN is a transcription factor that plays key roles in both normal development and cancer. In neuroblastoma, MYCN acts as a major oncogenic driver through pleiotropic effects controlled by multiple protein encoding genes as well as microRNAs (miRNAs). MYCN activity is tightly regulated at the level of transcription and protein stability through various mechanisms. Like most genes, MYCN is further controlled by miRNAs, but the full complement of all miRNAs implicated in this process has not been determined through an unbiased approach. To elucidate the role of miRNAs in regulation of MYCN, we thus explored the MYCN-miRNA interactome to establish miRNAs controlling MYCN expression levels. We combined results from an unbiased and genome-wide high-throughput miRNA target reporter screen with miRNA and mRNA expression data from patients and a murine neuroblastoma progression model. We identified 29 miRNAs targeting MYCN, of which 12 miRNAs are inversely correlated with MYCN expression or activity in neuroblastoma tumor tissue. The majority of MYCN-targeting miRNAs in neuroblastoma showed a decrease in expression during murine MYCN-driven neuroblastoma tumor development. Therefore, we provide evidence that MYCN-targeting miRNAs are preferentially downregulated in MYCN-driven neuroblastoma, suggesting that MYCN negatively controls the expression of these miRNAs, to safeguard its expression

An Unbiased Survey of 500 Nearby Stars for Debris Disks: A JCMT Legacy Program

We present the scientific motivation and observing plan for an upcoming detection survey for debris disks using the James Clerk Maxwell Telescope. The SCUBA-2 Unbiased Nearby Stars (SUNS) Survey will observe 500 nearby main sequence and sub-giant stars (100 of each of the A, F, G, K and M spectral classes) to the 850 micron extragalactic confusion limit to search for evidence of submillimeter excess, an indication of circumstellar material. The survey distance boundaries are 8.6, 16.5, 22, 25 and 45 pc for M, K, G, F and A stars, respectively, and all targets lie between the declinations of -40 deg to 80 deg. In this survey, no star will be rejected based on its inherent properties: binarity, presence of planetary companions, spectral type or age. This will be the first unbiased survey for debris disks since IRAS. We expect to detect ~125 debris disks, including ~50 cold disks not detectable in current shorter wavelength surveys. A substantial amount of complementary data will be required to constrain the temperatures and masses of discovered disks. High resolution studies will likely be required to resolve many of the disks. Therefore, these systems will be the focus of future observational studies using a variety of observatories to characterize their physical properties. For non-detected systems, this survey will set constraints (upper limits) on the amount of circumstellar dust, of typically 200 times the Kuiper Belt mass, but as low as 10 times the Kuiper Belt mass for the nearest stars in the sample (approximately 2 pc).Comment: 11 pages, 7 figures (3 color), accepted by the Publications of the Astronomical Society of the Pacifi