91 research outputs found

    Thermal power systems small power systems application project: Siting issues for solar thermal power plants with small community applications

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    The siting issues associated with small, dispersed solar thermal power plants for utility/small community applications of less than 10 MWe are reported. Some specific requirements are refered to the first engineering experiment for the Small Power Systems Applications (SPSA) Project. The background for the subsequent issue discussions is provided. The SPSA Project and the requirements for the first engineering experiment are described, and the objectives and scope for the report as a whole. A overview of solar thermal technologies and some technology options are discussed

    Siting Issues for Solar Thermal Power Plants with Small Community Applications

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    Technologies for solar thermal plants are being developed to provide energy alternatives for the future. Implementation of these plants requires consideration of siting issues as well as power system technology. While many conventional siting considerations are applicable, there is also a set of unique siting issues for solar thermal plants. Early experimental plants will have special siting considerations. The siting issues associated with small, dispersed solar thermal power plants in the 1 to 10 MWe power range for utility/small community applications are considered. Some specific requirements refer to the first 1 MWe engineering experiment for the Small Power Systems Applications (SPSA) Project. The siting issues themselves are discussed in three categories: (1) system resource requirements, (2) environmental effects on the system, and (3) potential impact of the plant on the environment. Within these categories, specific issues are discussed in a qualitative manner. Examples of limiting factors for some issues are taken from studies of other solar systems

    Organometallic iridium(III) anticancer complexes with new mechanisms of action: NCI-60 screening, mitochondrial targeting, and apoptosis

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    Platinum complexes related to cisplatin, cis-[PtCl2(NH3)2], are successful anticancer drugs; however, other transition metal complexes offer potential for combating cisplatin resistance, decreasing side effects, and widening the spectrum of activity. Organometallic half-sandwich iridium (IrIII) complexes [Ir(Cpx)(XY)Cl]+/0 (Cpx = biphenyltetramethylcyclopentadienyl and XY = phenanthroline (1), bipyridine (2), or phenylpyridine (3)) all hydrolyze rapidly, forming monofunctional G adducts on DNA with additional intercalation of the phenyl substituents on the Cpx ring. In comparison, highly potent complex 4 (Cpx = phenyltetramethylcyclopentadienyl and XY = N,N-dimethylphenylazopyridine) does not hydrolyze. All show higher potency toward A2780 human ovarian cancer cells compared to cisplatin, with 1, 3, and 4 also demonstrating higher potency in the National Cancer Institute (NCI) NCI-60 cell-line screen. Use of the NCI COMPARE algorithm (which predicts mechanisms of action (MoAs) for emerging anticancer compounds by correlating NCI-60 patterns of sensitivity) shows that the MoA of these IrIII complexes has no correlation to cisplatin (or oxaliplatin), with 3 and 4 emerging as particularly novel compounds. Those findings by COMPARE were experimentally probed by transmission electron microscopy (TEM) of A2780 cells exposed to 1, showing mitochondrial swelling and activation of apoptosis after 24 h. Significant changes in mitochondrial membrane polarization were detected by flow cytometry, and the potency of the complexes was enhanced ca. 5× by co-administration with a low concentration (5 μM) of the γ-glutamyl cysteine synthetase inhibitor L-buthionine sulfoximine (L-BSO). These studies reveal potential polypharmacology of organometallic IrIII complexes, with MoA and cell selectivity governed by structural changes in the chelating ligands

    Functional Categories Associated with Clusters of Genes That Are Co-Expressed across the NCI-60 Cancer Cell Lines

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    The NCI-60 is a panel of 60 diverse human cancer cell lines used by the U.S. National Cancer Institute to screen compounds for anticancer activity. In the current study, gene expression levels from five platforms were integrated to yield a single composite transcriptome profile. The comprehensive and reliable nature of that dataset allows us to study gene co-expression across cancer cell lines.Hierarchical clustering revealed numerous clusters of genes in which the genes co-vary across the NCI-60. To determine functional categorization associated with each cluster, we used the Gene Ontology (GO) Consortium database and the GoMiner tool. GO maps genes to hierarchically-organized biological process categories. GoMiner can leverage GO to perform ontological analyses of gene expression studies, generating a list of significant functional categories.GoMiner analysis revealed many clusters of coregulated genes that are associated with functional groupings of GO biological process categories. Notably, those categories arising from coherent co-expression groupings reflect cancer-related themes such as adhesion, cell migration, RNA splicing, immune response and signal transduction. Thus, these clusters demonstrate transcriptional coregulation of functionally-related genes

    Competition between Replicative and Translesion Polymerases during Homologous Recombination Repair in Drosophila

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    In metazoans, the mechanism by which DNA is synthesized during homologous recombination repair of double-strand breaks is poorly understood. Specifically, the identities of the polymerase(s) that carry out repair synthesis and how they are recruited to repair sites are unclear. Here, we have investigated the roles of several different polymerases during homologous recombination repair in Drosophila melanogaster. Using a gap repair assay, we found that homologous recombination is impaired in Drosophila lacking DNA polymerase zeta and, to a lesser extent, polymerase eta. In addition, the Pol32 protein, part of the polymerase delta complex, is needed for repair requiring extensive synthesis. Loss of Rev1, which interacts with multiple translesion polymerases, results in increased synthesis during gap repair. Together, our findings support a model in which translesion polymerases and the polymerase delta complex compete during homologous recombination repair. In addition, they establish Rev1 as a crucial factor that regulates the extent of repair synthesis

    Consensus-Phenotype Integration of Transcriptomic and Metabolomic Data Implies a Role for Metabolism in the Chemosensitivity of Tumour Cells

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    Using transcriptomic and metabolomic measurements from the NCI60 cell line panel, together with a novel approach to integration of molecular profile data, we show that the biochemical pathways associated with tumour cell chemosensitivity to platinum-based drugs are highly coincident, i.e. they describe a consensus phenotype. Direct integration of metabolome and transcriptome data at the point of pathway analysis improved the detection of consensus pathways by 76%, and revealed associations between platinum sensitivity and several metabolic pathways that were not visible from transcriptome analysis alone. These pathways included the TCA cycle and pyruvate metabolism, lipoprotein uptake and nucleotide synthesis by both salvage and de novo pathways. Extending the approach across a wide panel of chemotherapeutics, we confirmed the specificity of the metabolic pathway associations to platinum sensitivity. We conclude that metabolic phenotyping could play a role in predicting response to platinum chemotherapy and that consensus-phenotype integration of molecular profiling data is a powerful and versatile tool for both biomarker discovery and for exploring the complex relationships between biological pathways and drug response
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