Torsional oscillator experiment on superfluid 4He confined in a porous alumina nanopore array

26th International Conferenceon Low Temperature Physics (LT26

Advanced Burner Test Reactor Preconceptual Design Report.

The goals of the Global Nuclear Energy Partnership (GNEP) are to expand the use of nuclear energy to meet increasing global energy demand, to address nuclear waste management concerns and to promote non-proliferation. Implementation of the GNEP requires development and demonstration of three major technologies: (1) Light water reactor (LWR) spent fuel separations technologies that will recover transuranics to be recycled for fuel but not separate plutonium from other transuranics, thereby providing proliferation-resistance; (2) Advanced Burner Reactors (ABRs) based on a fast spectrum that transmute the recycled transuranics to produce energy while also reducing the long term radiotoxicity and decay heat loading in the repository; and (3) Fast reactor fuel recycling technologies to recover and refabricate the transuranics for repeated recycling in the fast reactor system. The primary mission of the ABR Program is to demonstrate the transmutation of transuranics recovered from the LWR spent fuel, and hence the benefits of the fuel cycle closure to nuclear waste management. The transmutation, or burning of the transuranics is accomplished by fissioning and this is most effectively done in a fast spectrum. In the thermal spectrum of commercial LWRs, some transuranics capture neutrons and become even heavier transuranics rather than being fissioned. Even with repeated recycling, only about 30% can be transmuted, which is an intrinsic limitation of all thermal spectrum reactors. Only in a fast spectrum can all transuranics be effectively fissioned to eliminate their long-term radiotoxicity and decay heat. The Advanced Burner Test Reactor (ABTR) is the first step in demonstrating the transmutation technologies. It directly supports development of a prototype full-scale Advanced Burner Reactor, which would be followed by commercial deployment of ABRs. The primary objectives of the ABTR are: (1) To demonstrate reactor-based transmutation of transuranics as part of an advanced fuel cycle; (2) To qualify the transuranics-containing fuels and advanced structural materials needed for a full-scale ABR; and (3) To support the research, development and demonstration required for certification of an ABR standard design by the U.S. Nuclear Regulatory Commission. The ABTR should also address the following additional objectives: (1) To incorporate and demonstrate innovative design concepts and features that may lead to significant improvements in cost, safety, efficiency, reliability, or other favorable characteristics that could promote public acceptance and future private sector investment in ABRs; (2) To demonstrate improved technologies for safeguards and security; and (3) To support development of the U.S. infrastructure for design, fabrication and construction, testing and deployment of systems, structures and components for the ABRs. Based on these objectives, a pre-conceptual design of a 250 MWt ABTR has been developed; it is documented in this report. In addition to meeting the primary and additional objectives listed above, the lessons learned from fast reactor programs in the U.S. and worldwide and the operating experience of more than a dozen fast reactors around the world, in particular the Experimental Breeder Reactor-II have been incorporated into the design of the ABTR to the extent possible

Regulated Expression of CCL21 in the Prostate Tumor Microenvironment Inhibits Tumor Growth and Metastasis in an Orthotopic Model of Prostate Cancer

Currently there are no curative therapies available for patients with metastatic prostate cancer. Thus, novel therapies are needed to treat this patient population. Immunotherapy represents one promising approach for the elimination of occult metastatic tumors. However, the prostate tumor microenvironment (TME) represents a hostile environment capable of suppressing anti-tumor immunity and effector cell function. In view of this immunosuppressive activity, we engineered murine prostate cancer cells with regulated expression (tet-on) of CCL21. Prostate tumor cells implanted orthotopically produced primary prostate tumors with predictable metastatic disease in draining lymph nodes and distant organs. Expression of CCL21 in the prostate TME enhanced survival, inhibited tumor growth and decreased the frequency of local (draining lymph node) and distant metastasis. Therefore, these studies provide a strong rationale for further evaluation of CCL21 in tumor immunity and its use in cancer immunotherapy

DNA Methylation Dynamics in Human Induced Pluripotent Stem Cells over Time

Epigenetic reprogramming is a critical event in the generation of induced pluripotent stem cells (iPSCs). Here, we determined the DNA methylation profiles of 22 human iPSC lines derived from five different cell types (human endometrium, placental artery endothelium, amnion, fetal lung fibroblast, and menstrual blood cell) and five human embryonic stem cell (ESC) lines, and we followed the aberrant methylation sites in iPSCs for up to 42 weeks. The iPSCs exhibited distinct epigenetic differences from ESCs, which were caused by aberrant methylation at early passages. Multiple appearances and then disappearances of random aberrant methylation were detected throughout iPSC reprogramming. Continuous passaging of the iPSCs diminished the differences between iPSCs and ESCs, implying that iPSCs lose the characteristics inherited from the parent cells and adapt to very closely resemble ESCs over time. Human iPSCs were gradually reprogrammed through the “convergence” of aberrant hyper-methylation events that continuously appeared in a de novo manner. This iPS reprogramming consisted of stochastic de novo methylation and selection/fixation of methylation in an environment suitable for ESCs. Taken together, random methylation and convergence are driving forces for long-term reprogramming of iPSCs to ESCs

Spotlight on Differentially Expressed Genes in Urinary Bladder Cancer

INTRODUCTION: We previously identified common differentially expressed (DE) genes in bladder cancer (BC). In the present study we analyzed in depth, the expression of several groups of these DE genes. MATERIALS AND METHODS: Samples from 30 human BCs and their adjacent normal tissues were analyzed by whole genome cDNA microarrays, qRT-PCR and Western blotting. Our attention was focused on cell-cycle control and DNA damage repair genes, genes related to apoptosis, signal transduction, angiogenesis, as well as cellular proliferation, invasion and metastasis. Four publicly available GEO Datasets were further analyzed, and the expression data of the genes of interest (GOIs) were compared to those of the present study. The relationship among the GOI was also investigated. GO and KEGG molecular pathway analysis was performed to identify possible enrichment of genes with specific biological themes. RESULTS: Unsupervised cluster analysis of DNA microarray data revealed a clear distinction in BC vs. control samples and low vs. high grade tumors. Genes with at least 2-fold differential expression in BC vs. controls, as well as in non-muscle invasive vs. muscle invasive tumors and in low vs. high grade tumors, were identified and ranked. Specific attention was paid to the changes in osteopontin (OPN, SPP1) expression, due to its multiple biological functions. Similarly, genes exhibiting equal or low expression in BC vs. the controls were scored. Significant pair-wise correlations in gene expression were scored. GO analysis revealed the multi-facet character of the GOIs, since they participate in a variety of mechanisms, including cell proliferation, cell death, metabolism, cell shape, and cytoskeletal re-organization. KEGG analysis revealed that the most significant pathway was that of Bladder Cancer (p = 1.5×10(-31)). CONCLUSIONS: The present work adds to the current knowledge on molecular signature identification of BC. Such works should progress in order to gain more insight into disease molecular mechanisms

Circulating IgM Requires Plasma Membrane Disruption to Bind Apoptotic and Non-Apoptotic Nucleated Cells and Erythrocytes

<div><p>Autoimmunity is associated with defective phagocytic clearance of apoptotic cells. IgM deficient mice exhibit an autoimmune phenotype consistent with a role for circulating IgM antibodies in apoptotic cell clearance. We have extensively characterised IgM binding to non-apoptotic and apoptotic mouse thymocytes and human Jurkat cells using flow cytometry, confocal imaging and electron microscopy. We demonstrate strong specific IgM binding to a subset of Annexin-V (AnnV)⁺PI (Propidium Iodide)⁺ apoptotic cells with disrupted cell membranes. Electron microscopy studies indicated that IgM⁺AnnV⁺PI⁺ apoptotic cells exhibited morphologically advanced apoptosis with marked plasma membrane disruption compared to IgM^-AnnV⁺PI⁺ apoptotic cells, suggesting that access to intracellular epitopes is required for IgM to bind. Strong and comparable binding of IgM to permeabilised non-apoptotic and apoptotic cells suggests that IgM bound epitopes are 'apoptosis independent' such that IgM may bind any cell with profound disruption of cell plasma membrane integrity. In addition, permeabilised erythrocytes exhibited significant IgM binding thus supporting the importance of cell membrane epitopes. These data suggest that IgM may recognize and tag damaged nucleated cells or erythrocytes that exhibit significant cell membrane disruption. The role of IgM <i>in vivo</i> in conditions characterized by severe cell damage such as ischemic injury, sepsis and thrombotic microangiopathies merits further exploration.</p></div