Underground nuclear power plant siting

This study is part of a larger evaluation of the problems associated with siting nuclear power plants in the next few decades. This evaluation is being undertaken by the Environmental Quality Laboratory of the California Institute of Technology in conjunction with The Aerospace Corporation and several other organizations. Current efforts are directed toward novel approaches to siting plants within the State of California. This report contains the results of efforts performed by The Aerospace Corporation to provide input information to the larger evaluation relative to underground siting of large central station nuclear power plants. Projections of electric power demand in California and the country as a whole suggest that a major increase in generating capacity will be required. The problem is complicated beyond that of a large but straightforward extension of capital investment by increased emphasis on environmental factors combined with the early stage of commercial application and regulation of nuclear power sources. Hydroelectric power generation is limited by the availability of suitable sites, and fossil fueled plants are constrained by the availability of high quality fuels and the adverse environmental and/or economic impact from the use of more plentiful fuels. A substantial increase in the number of nuclear power plants is now under way. This source of power is expected to provide the maj or portion of increased capacity. Other power sources such as geothermal and nuclear fusion are unlikely to satisfy the national needs due to technical problems and the lack of a comprehensive development program. There are several problems associated with meeting the projected power demand. Chief among these is the location of acceptable and economic plant sites. Indeed a sufficient number of sites may not be found unless changes occur in the procedures for selecting sites, the criteria for accepting sites, or the type of site required. Placement of a nuclear plant underground has been suggested as an alternative to present siting practices. It is postulated that the advantages of underground siting in some situations may more than compensate for added costs so that such facilities could be preferred even where surface sites are available. By virtue of greater safety, reduced surface area requirements, and improved aesthetics, underground sites might also be found where acceptable surface sites are not available. Four small European reactors have been constructed partially underground but plans for large size commercial plants have not progressed. Consequently, the features of underground power plant siting are not well understood. Gross physical features such as depth of burial, number and size of excavated galleries, equipment layout, and access or exit shafts/tunnels must be specified. Structural design features of the gallery liners, containment structure, foundations, and gallery interconnections must also be identified. Identification of the nuclear, electrical, and support equipment appropriate to underground operation is needed. Operational features must be defined for normal operations, refueling, and construction. Several magazine articles have been published addressing underground concepts. but adequate engineering data is not available to support an evaluation of the underground concept. There also remain several unresolved questions relative to the advantages of underground siting as well as the costs and other possible penalties associated with this novel approach to siting. These include the degree of increased safety through improved containment; the extent and value of isolation from falling objects, e. g. aircraft; the value of isolation from surface storms and tidal waves; the value of protection from vandalism or sabotage; the extent by which siting constraints are relieved through reduced population-distance requirements or aggravated by underground construction requirements; and the value to be placed upon the aesthetic differences of a less visible facility. The study described in this report has been directed toward some of these questions and uncertainties. Within the study an effort has been made to identify viable configurations and structural liners for typical light water reactor nuclear power plants. Three configurations are summarized in Section 3. A discussion of the underground gallery liner design and associated structural analyses is presented in Section 4. Also addressed in the study and discussed in Section 5 are some aspects of containment for underground plants. There it is suggested that the need for large separations between the plant and population centers may be significantly reduced, or perhaps eliminated. Section 6 contains a brief discussion of operational considerations for underground plants. The costs associated with excavation and lining of the underground galleries have been estimated in Section 7. These estimates include an assessment of variations implied by different seismic loading assumptions and differences in geologic media. It is shown that these costs are a small percentage of the total cost of comparable surface plants. Finally, the parameters characterizing an acceptable underground site are discussed in Section 8. Material is also included in the appendices pertaining to foreign underground plants, span limits of underground excavations, potential siting areas for underground plants in the State of California, pertinent data from the Underground Nuclear Test Program, and other supporting technical discussions

High-throughput screening with the Eimeria tenella CDC2-related kinase2/cyclin complex EtCRK2/EtCYC3a

The poultry disease coccidiosis, caused by infection with Eimeria spp. apicomplexan parasites, is responsible for enormous economic losses to the global poultry industry. The rapid increase of resistance to therapeutic agents, as well as the expense of vaccination with live attenuated vaccines, requires the development of new effective treatments for coccidiosis. Because of their key regulatory function in the eukaryotic cell cycle, cyclin-dependent kinases (CDKs) are prominent drug targets. The Eimeria tenella CDC2-related kinase 2 (EtCRK2) is a validated drug target that can be activated in vitro by the CDK activator XlRINGO (Xenopus laevis rapid inducer of G2/M progression in oocytes). Bioinformatics analyses revealed four putative E. tenella cyclins (EtCYCs) that are closely related to cyclins found in the human apicomplexan parasite Plasmodium falciparum. EtCYC3a was cloned, expressed in Escherichia coli and purified in a complex with EtCRK2. Using the non-radioactive time-resolved fluorescence energy transfer (TR-FRET) assay, we demonstrated the ability of EtCYC3a to activate EtCRK2 as shown previously for XlRINGO. The EtCRK2/EtCYC3a complex was used for a combined in vitro and in silico high-throughput screening approach, which resulted in three lead structures, a naphthoquinone, an 8-hydroxyquinoline and a 2-pyrimidinyl-aminopiperidine-propane-2-ol. This constitutes a promising starting point for the subsequent lead optimization phase and the development of novel anticoccidial drugs

Large-Scale Atomistic Simulations of Environmental Effects on the Formation and Properties of Molecular Junctions

Using an updated simulation tool, we examine molecular junctions comprised of benzene-1,4-dithiolate bonded between gold nanotips, focusing on the importance of environmental factors and inter-electrode distance on the formation and structure of bridged molecules. We investigate the complex relationship between monolayer density and tip separation, finding that the formation of multi-molecule junctions is favored at low monolayer density, while single-molecule junctions are favored at high density. We demonstrate that tip geometry and monolayer interactions, two factors that are often neglected in simulation, affect the bonding geometry and tilt angle of bridged molecules. We further show that the structures of bridged molecules at 298 and 77 K are similar.Comment: To appear in ACS Nano, 30 pages, 5 figure

A High-Resolution Map of Segmental DNA Copy Number Variation in the Mouse Genome

Submicroscopic (less than 2 Mb) segmental DNA copy number changes are a recently recognized source of genetic variability between individuals. The biological consequences of copy number variants (CNVs) are largely undefined. In some cases, CNVs that cause gene dosage effects have been implicated in phenotypic variation. CNVs have been detected in diverse species, including mice and humans. Published studies in mice have been limited by resolution and strain selection. We chose to study 21 well-characterized inbred mouse strains that are the focus of an international effort to measure, catalog, and disseminate phenotype data. We performed comparative genomic hybridization using long oligomer arrays to characterize CNVs in these strains. This technique increased the resolution of CNV detection by more than an order of magnitude over previous methodologies. The CNVs range in size from 21 to 2,002 kb. Clustering strains by CNV profile recapitulates aspects of the known ancestry of these strains. Most of the CNVs (77.5%) contain annotated genes, and many (47.5%) colocalize with previously mapped segmental duplications in the mouse genome. We demonstrate that this technique can identify copy number differences associated with known polymorphic traits. The phenotype of previously uncharacterized strains can be predicted based on their copy number at these loci. Annotation of CNVs in the mouse genome combined with sequence-based analysis provides an important resource that will help define the genetic basis of complex traits

Population policies and education: exploring the contradictions of neo-liberal globalisation

The world is increasingly characterised by profound income, health and social inequalities (Appadurai, 2000). In recent decades development initiatives aimed at reducing these inequalities have been situated in a context of increasing globalisation with a dominant neo-liberal economic orthodoxy. This paper argues that neo-liberal globalisation contains inherent contradictions regarding choice and uniformity. This is illustrated in this paper through an exploration of the impact of neo-liberal globalisation on population policies and programmes. The dominant neo-liberal economic ideology that has influenced development over the last few decades has often led to alternative global visions being overlooked. Many current population and development debates are characterised by polarised arguments with strongly opposing aims and views. This raises the challenge of finding alternatives situated in more middle ground that both identify and promote the socially positive elements of neo-liberalism and state intervention, but also to limit their worst excesses within the population field and more broadly. This paper concludes with a discussion outling the positive nature of middle ground and other possible alternatives

The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study

Midostaurin (PKC412A), N-benzoyl-staurosporine, potently inhibits protein kinase C alpha (PKCα), VEGFR2, KIT, PDGFR and FLT3 tyrosine kinases. In mice, midostaurin slows growth and delays lung metastasis of melanoma cell lines. We aimed to test midostaurin's safety, efficacy and biologic activity in a Phase IIA clinical trial in patients with metastatic melanoma. Seventeen patients with advanced metastatic melanoma received midostaurin 75 mg p.o. t.i.d., unless toxicity or disease progression supervened. Patient safety was assessed weekly, and tumour response was assessed clinically or by CT. Tumour biopsies and plasma samples obtained at entry and after 4 weeks were analysed for midostaurin concentration, PKC activity and multidrug resistance. No tumour responses were seen. Two (12%) patients had stable disease for 50 and 85 days, with minor response in one. The median overall survival was 43 days. Seven (41%) discontinued treatment with potential toxicity, including nausea, vomiting, diarrhoea and/or fatigue. One patient had >50% reduction in PKC activity. Tumour biopsies showed two PKC isoforms relatively insensitive to midostaurin, out of three patients tested. No modulation of multidrug resistance was demonstrated. At this dose schedule, midostaurin did not show clinical or biologic activity against metastatic melanoma. This negative trial reinforces the importance of correlating biologic and clinical responses in early clinical trials of targeted therapies

High-resolution genome-wide cytosine methylation profiling with simultaneous copy number analysis and optimization for limited cell numbers

Many genome-wide assays involve the generation of a subset (or representation) of the genome following restriction enzyme digestion. The use of enzymes sensitive to cytosine methylation allows high-throughput analysis of this epigenetic regulatory process. We show that the use of a dual-adapter approach allows us to generate genomic representations that includes fragments of <200 bp in size, previously not possible when using the standard approach of using a single adapter. By expanding the representation to smaller fragments using HpaII or MspI, we increase the representation by these isoschizomers to more than 1.32 million loci in the human genome, representing 98.5% of CpG islands and 91.1% of refSeq promoters. This advance allows the development of a new, high-resolution version of our HpaII-tiny fragment Enrichment by Ligation-mediated PCR (HELP) assay to study cytosine methylation. We also show that the MspI representation generates information about copy-number variation, that the assay can be used on as little as 10 ng of DNA and that massively parallel sequencing can be used as an alternative to microarrays to read the output of the assay, making this a powerful discovery platform for studies of genomic and epigenomic abnormalities