Hanford Site National Environmental Policy Act (NEPA) characterization. Revision 9

This ninth revision of the Hanford Site National Environmental Policy Act (NEPA) Characterization presents current environmental data regarding the hanford Site and its immediate environs. This information is intended for use in preparing Chapters 4 and 6 in Hanford Site-related NEPA documents. Chapter 4.0 (Affected Environment) includes information on climate and meteorology, geology, hydrology, ecology, cultural, archaeological and historical resources, socioeconomics, and noise. Chapter 6.0 (Statutory and Regulatory Requirements) provides the preparer with the federal and state regulations, DOE directives and permits, and environmental standards directly applicable to the NEPA documents on the Hanford Site. Not all of the sections have been updated for this revision. The following lists the updated sections: climate and meteorology; ecology (threatened and endangered species section only); culture, archaeological, and historical resources; socioeconomics; all of Chapter 6

Hanford Site National Environmental Policy Act (NEPA) characterization. Revision 10

This document describes the US Department of Energy`s (DOE) Hanford Site environment and is numbered to correspond to the chapters where such information is presented in Hanford Site NEPA related documents. The document is intended to provide a consistent description of the Hanford Site environment for the many NEPA documents that are being prepared by contractors. The two chapters in this document (Chapters 4 and 6) are numbered this way to correspond to the chapters where such information is presented in environmental impact statements (EISs) and other Site-related NEPA or CERCLA documentation. Chapter 4.0 (Affected Environment) describes the Hanford Site environment, and includes information on climate and meteorology, geology, hydrology, ecology, cultural, archaeological and historical resources, socioeconomics, and noise. Chapter 6.0 (Statutory and Regulatory Requirements) describes applicable federal and state laws and regulations, DOE directives and permits, and environmental standards directly applicable to the NEPA documents on the Hanford Site

Hanford Site National Environmental Policy Act (NEPA) characterization. Revision 10

This document describes the US Department of Energy`s (DOE) Hanford Site environment and is numbered to correspond to the chapters where such information is presented in Hanford Site NEPA related documents. The document is intended to provide a consistent description of the Hanford Site environment for the many NEPA documents that are being prepared by contractors. The two chapters in this document (Chapters 4 and 6) are numbered this way to correspond to the chapters where such information is presented in environmental impact statements (EISs) and other Site-related NEPA or CERCLA documentation. Chapter 4.0 (Affected Environment) describes the Hanford Site environment, and includes information on climate and meteorology, geology, hydrology, ecology, cultural, archaeological and historical resources, socioeconomics, and noise. Chapter 6.0 (Statutory and Regulatory Requirements) describes applicable federal and state laws and regulations, DOE directives and permits, and environmental standards directly applicable to the NEPA documents on the Hanford Site

Hanford Site National Environmental Policy Act (NEPA) characterization. Revision 8

This eighth revision of the Hanford Site National Environmental Policy Act (NEPA) Characterization presents current environmental data regarding the Hanford Site and its immediate environs. This information is intended for use in preparing Chapters 4 and 6 in Hanford Site-related NEPA documents. Chapter 4 (Affected Environment) includes information on climate and meteorology, geology, hydrology, ecology, historical, archaeological and cultural resources, socioeconomics, and noise. Chapter 6 (Statutory and Regulatory Requirements) provides the preparer with the federal and state regulations, DOE directives and permits, and environmental standards directly applicable to the NEPA documents on the Hanford Site. The following sections were updated in this revision: climate and meteorology; ecology (threatened and endangered species section only); historical; archaeological and cultural resources; and all of chapter 6. No conclusions or recommendations are given in this report. Rather, it is a compilation of information on the Hanford Site environment that can be used directly by Site contractors. This information can also be used by any interested individual seeking baseline data on the hanford Site and its past activities by which to evaluate projected activities and their impacts

Radiological Assessment System for Consequence Analysis (RASCAL) Version 3.0

The Radiological Assessment System for Consequence AnaLysis, Version 3.0 (RASCAL 3.0) is the U.S. Nuclear Regulatory Commission�s (NRC) main computational tool for use during radiological emergencies. RASCAL estimates doses from radiological accidents for comparison with Protective Action Guides and acute health effects thresholds. It includes six computational tools: ST-Dose, FM-Dose, Decay, BackCalc, UF6Plume, and MetProc. ST-Dose computes time-dependent nuclide release rates, atmospheric transport, radiological decay, and doses. FM-Dose computes doses from environmental concentrations of nuclides. Decay computes radiological decay and daughter in-growth. BackCalc estimates a distribution of possible release rates from field measurements. UF6Plume computes uranium exposures and HF concentrations from a UF6 release. MetProc prepares meteorological data for use by ST-Dose and UF6Plume

An orbital-free molecular dynamics study of melting in K_20, K_55, K_92, K_142, Rb_55 and Cs_55 clusters

The melting-like transition in potasium clusters K_N, with N=20, 55, 92 and 142, is studied by using an orbital-free density-functional constant-energy molecular dynamics simulation method, and compared to previous theoretical results on the melting-like transition in sodium clusters of the same sizes. Melting in potasium and sodium clusters proceeds in a similar way: a surface melting stage develops upon heating before the homogeneous melting temperature is reached. Premelting effects are nevertheless more important and more easily established in potasium clusters, and the transition regions spread over temperature intervals which are wider than in the case of sodium. For all the sizes considered, the percentage melting temperature reduction when passing from Na to K clusters is substantially larger than in the bulk. Once those two materials have been compared for a number of different cluster sizes, we study the melting-like transition in Rb_55 and Cs_55 clusters and make a comparison with the melting behavior of Na_55 and K_55. As the atomic number increases, the height of the specific heat peaks decreases, their width increases, and the melting temperature decreases as in bulk melting, but in a more pronounced way.Comment: LaTeX file. 6 pages with 17 pictures. Final version with minor change

Launching a Novel Preclinical Infrastructure: Comparative Oncology Trials Consortium Directed Therapeutic Targeting of TNFα to Cancer Vasculature

Background: Under the direction and sponsorship of the National Cancer Institute, we report on the first pre-clinical trial of the Comparative Oncology Trials Consortium (COTC). The COTC is a novel infrastructure to integrate cancers that naturally develop in pet dogs into the development path of new human drugs. Trials are designed to address questions challenging in conventional preclinical models and early phase human trials. Large animal spontaneous cancer models can be a valuable addition to successful studies of cancer biology and novel therapeutic drug, imaging and device development. Methodology/Principal Findings: Through this established infrastructure, the first trial of the COTC (COTC001) evaluated a targeted AAV-phage vector delivering tumor necrosis factor (RGD-A-TNF) to αV integrins on tumor endothelium. Trial progress and data was reviewed contemporaneously using a web-enabled electronic reporting system developed for the consortium. Dose-escalation in cohorts of 3 dogs (n = 24) determined an optimal safe dose (5 x 1012 transducing units intravenous) of RGD-A-TNF. This demonstrated selective targeting of tumor-associated vasculature and sparing of normal tissues assessed via serial biopsy of both tumor and normal tissue. Repetitive dosing in a cohort of 14 dogs, at the defined optimal dose, was well tolerated and led to objective tumor regression in two dogs (14%), stable disease in six (43%), and disease progression in six (43%) via Response Evaluation Criteria in Solid Tumors (RECIST). Conclusions/Significance: The first study of the COTC has demonstrated the utility and efficiency of the established infrastructure to inform the development of new cancer drugs within large animal naturally occurring cancer models. The preclinical evaluation of RGD-A-TNF within this network provided valuable and necessary data to complete the design of first-in-man studies

Gene expression profiling identifies inflammation and angiogenesis as distinguishing features of canine hemangiosarcoma

<p>Abstract</p> <p>Background</p> <p>The etiology of hemangiosarcoma remains incompletely understood. Its common occurrence in dogs suggests predisposing factors favor its development in this species. These factors could represent a constellation of heritable characteristics that promote transformation events and/or facilitate the establishment of a microenvironment that is conducive for survival of malignant blood vessel-forming cells. The hypothesis for this study was that characteristic molecular features distinguish hemangiosarcoma from non-malignant endothelial cells, and that such features are informative for the etiology of this disease.</p> <p>Methods</p> <p>We first investigated mutations of VHL and Ras family genes that might drive hemangiosarcoma by sequencing tumor DNA and mRNA (cDNA). Protein expression was examined using immunostaining. Next, we evaluated genome-wide gene expression profiling using the Affymetrix Canine 2.0 platform as a global approach to test the hypothesis. Data were evaluated using routine bioinformatics and validation was done using quantitative real time RT-PCR.</p> <p>Results</p> <p>Each of 10 tumor and four non-tumor samples analyzed had wild type sequences for these genes. At the genome wide level, hemangiosarcoma cells clustered separately from non-malignant endothelial cells based on a robust signature that included genes involved in inflammation, angiogenesis, adhesion, invasion, metabolism, cell cycle, signaling, and patterning. This signature did not simply reflect a cancer-associated angiogenic phenotype, as it also distinguished hemangiosarcoma from non-endothelial, moderately to highly angiogenic bone marrow-derived tumors (lymphoma, leukemia, osteosarcoma).</p> <p>Conclusions</p> <p>The data show that inflammation and angiogenesis are important processes in the pathogenesis of vascular tumors, but a definitive ontogeny of the cells that give rise to these tumors remains to be established. The data do not yet distinguish whether functional or ontogenetic plasticity creates this phenotype, although they suggest that cells which give rise to hemangiosarcoma modulate their microenvironment to promote tumor growth and survival. We propose that the frequent occurrence of canine hemangiosarcoma in defined dog breeds, as well as its similarity to homologous tumors in humans, offers unique models to solve the dilemma of stem cell plasticity and whether angiogenic endothelial cells and hematopoietic cells originate from a single cell or from distinct progenitor cells.</p

Gene Expression Profiles of Sporadic Canine Hemangiosarcoma Are Uniquely Associated with Breed

The role an individual's genetic background plays on phenotype and biological behavior of sporadic tumors remains incompletely understood. We showed previously that lymphomas from Golden Retrievers harbor defined, recurrent chromosomal aberrations that occur less frequently in lymphomas from other dog breeds, suggesting spontaneous canine tumors provide suitable models to define how heritable traits influence cancer genotypes. Here, we report a complementary approach using gene expression profiling in a naturally occurring endothelial sarcoma of dogs (hemangiosarcoma). Naturally occurring hemangiosarcomas of Golden Retrievers clustered separately from those of non-Golden Retrievers, with contributions from transcription factors, survival factors, and from pro-inflammatory and angiogenic genes, and which were exclusively present in hemangiosarcoma and not in other tumors or normal cells (i.e., they were not due simply to variation in these genes among breeds). Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) was among genes preferentially enriched within known pathways derived from gene set enrichment analysis when characterizing tumors from Golden Retrievers versus other breeds. Heightened VEGFR1 expression in these tumors also was apparent at the protein level and targeted inhibition of VEGFR1 increased proliferation of hemangiosarcoma cells derived from tumors of Golden Retrievers, but not from other breeds. Our results suggest heritable factors mold gene expression phenotypes, and consequently biological behavior in sporadic, naturally occurring tumors

Establishment of canine hemangiosarcoma xenograft models expressing endothelial growth factors, their receptors, and angiogenesis-associated homeobox genes

<p>Abstract</p> <p>Background</p> <p>Human hemangiosarcoma (HSA) tends to have a poor prognosis; its tumorigenesis has not been elucidated, as there is a dearth of HSA clinical specimens and no experimental model for HSA. However, the incidence of spontaneous HSA is relatively high in canines; therefore, canine HSA has been useful in the study of human HSA. Recently, the production of angiogenic growth factors and their receptors in human and canine HSA has been reported. Moreover, the growth-factor environment of HSA is very similar to that of pathophysiological angiogenesis, which some homeobox genes regulate in the transcription of angiogenic molecules. In the present study, we established 6 xenograft canine HSA tumors and detected the expression of growth factors, their receptors, and angiogenic homeobox genes.</p> <p>Methods</p> <p>Six primary canine HSAs were xenografted to nude mice subcutaneously and serially transplanted. Subsequently, the expressions of vascular endothelial growth factor (VEGF)-A, basic fibroblast growth factors (bFGF), flt-1 and flk-1 (receptors of VEGF-A), FGFR-1, and angiogenic homeobox genes HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 were investigated in original and xenograft tumors by histopathology, immunostaining, and reverse transcription polymerase chain reaction (RT-PCR), using canine-specific primer sets.</p> <p>Results</p> <p>Histopathologically, xenograft tumors comprised a proliferation of neoplastic cells that were varied in shape, from spindle-shaped and polygonal to ovoid; some vascular-like structures and vascular clefts of channels were observed, similar to those in the original tumors. The expression of endothelial markers (CD31 and vWF) was detected in xenograft tumors by immunohistochemistry and RT-PCR. Moreover, the expression of VEGF-A, bFGF, flt-1, flk-1, FGFR-1, HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 was detected in xenograft tumors. Interestingly, expressions of bFGF tended to be higher in 3 of the xenograft HSA tumors than in the other tumors.</p> <p>Conclusion</p> <p>We established 6 xenograft canine HSA tumors in nude mice and found that the expressions of angiogenic growth factors and their receptors in xenograft HSAs were similar to those in spontaneous HSA. Furthermore, we detected the expression of angiogenic homeobox genes; therefore, xenograft models may be useful in analyzing malignant growth in HSA.</p