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Sample records for metabolism final progress

  1. 2001 Gordon Research Conference on Archaea: Ecology [sic], Metabolism. Final progress report [agenda and attendee list

    SciTech Connect

    Daniels, Charles

    2001-08-10

    The Gordon Research Conference on Archaea: Ecology, Metabolism [and Molecular Biology] was held at Proctor Academy, Andover, New Hampshire, August 5-10, 2001. The conference was attended by 135 participants. The attendees represented the spectrum of endeavor in this field, coming from academia, industry, and government laboratories, and included US and foreign scientists, senior researchers, young investigators, and students. Emphasis was placed on current unpublished research and discussion of the future target areas in this field. There was a conscious effort to stimulate discussion about the key issues in the field today. Session topics included the following: Ecology and genetic elements; Genomics and evolution; Ecology, genomes and gene regulation; Replication and recombination; Chromatin and transcription; Gene regulation; Post-transcription processing; Biochemistry and metabolism; Proteomics and protein structure; Metabolism and physiology. The featured speaker addressed the topic: ''Archaeal viruses, witnesses of prebiotic evolution?''

  2. Teratogen metabolism. Final report

    SciTech Connect

    Braun, A.G.

    1983-01-31

    This study indicates Thalidomide is metabolized by a classic cytochrome P450 monoxygenase system to a product which inhibits attachment of cells to concanavalin A coated dishes. Hydrolysis products of Thalidomide and its active metabolite do not inhibit attachement. We have initiated additional studies with methylene chloride extracts of particulate and of volatile hydrocarbon emissions of a domestic oil burner. These studies show low levels of inhibitory activity are uniformly present in these extracts.

  3. Final Progress Report

    SciTech Connect

    Josef Michl

    2011-10-31

    In this project we have established guidelines for the design on organic chromophores suitable for producing high triplet yields via singlet fission. We have proven their utility by identifying a chromophore of a structural class that had never been examined for singlet fission before, 1,3-diphenylisobenzofuran, and demonstrating in two independent ways that a thin layer of this material produces a triplet yield of 200% within experimental error. We have also designed a second chromophore of a very different type, again of a structural class that had not been examined for singlet fission before, and found that in a thin layer it produces a 70% triplet yield. Finally, we have enhanced the theoretical understanding of the quantum mechanical nature of the singlet fission process.

  4. Regulation of terpene metabolism. Progress report

    SciTech Connect

    Croteau, R.

    1983-01-01

    Progress is reported in the following research areas: function of monoterpene catabolism; pathways and enzymes of monoterpene catabolism; ultrastructure of oil glands; pathways and enzymes of monoterpene biosynthesis; and regulation of metabolism in peppermints. (ACR)

  5. IRIS Final Technical Progress Report

    SciTech Connect

    M. D. Carelli

    2003-11-03

    OAK-B135 This NERI project, originally started as the Secure Transportable Autonomous Light Water Reactor (STAR-LW) and currently known as the International Reactor Innovative and Secure (IRIS) project, had the objective of investigating a novel type of water-cooled reactor to satisfy the Generation IV goals: fuel cycle sustainability, enhanced reliability and safety, and improved economics. The research objectives over the three-year (1999-2002) program were as follows: First year: Assess various design alternatives and establish main characteristics of a point design; Second year: Perform feasibility and engineering assessment of the selected design solutions; Third year: Complete reactor design and performance evaluation, including cost assessment These objectives were fully attained and actually they served to launch IRIS as a full fledged project for eventual commercial deployment. The program did not terminate in 2002 at the end of the NERI program, and has just entered in its fifth year. This has been made possible by the IRIS project participants which have grown from the original four member, two-countries team to the current twenty members, nine countries consortium. All the consortium members work under their own funding and it is estimated that the value of their in-kind contributions over the life of the project has been of the order of $30M. Currently, approximately 100 people worldwide are involved in the project. A very important constituency of the IRIS project is the academia: 7 universities from four countries are members of the consortium and five more US universities are associated via parallel NERI programs. To date, 97 students have worked or are working on IRIS; 59 IRIS-related graduate theses have been prepared or are in preparation, and 41 of these students have already graduated with M.S. (33) or Ph.D. (8) degrees. This ''final'' report (final only as far as the NERI program is concerned) summarizes the work performed in the first four

  6. The toxicology and metabolism of nickel compounds: Final technical progress report for the period from 1 December 1985 to 31 August 1987

    SciTech Connect

    Sunderman, F.W. Jr.

    1987-09-01

    The toxicology of nickel compounds was investigated in rats and the metabolism of nickel was studied in humans. Lipid peroxidation is one of the molecular mechanisms of acute toxicity of NiCl/sub 2/ in rats. The thymus is a target organ of acute nickel toxicity, as evidenced by the thymic involution that occurs within 24 hours after parenteral administration of NiCl/sub 2/ to rats. The lung is the primary target organ of subacute nickel toxicity in rats, as manifested by marked bronchoalveolar proliferation and degenerative changes in the pulmonary vascular endothelium of rats after 3 to 6 weeks of daily sc injections of NiCl/sub 2/. Electrothermal atomic absorption spectrophotometry with Zeeman background correction provides an accurate, sensitive, and practical routine method for analysis of nickel concentrations in body fluids and tissues of human subjects to monitor environmental, occupational, or iatrogenic exposures to nickel compounds. 11 refs.

  7. 1995 PVUSA progress report. Final report

    SciTech Connect

    1996-03-01

    Photovoltaics for Utility Scale Applications (PVUSA) is a national public-private partnership that is assessing and demonstrating the viability of utility-scale (US) photovoltaic (PV) electric generation systems and recent developments in PV module technology. This report updates the project`s progress, reviews the status and performance of the various PV installations during 1995, summarizes key accomplishments and conclusions, and serves as the final report under Pacific Gas and Electric Company`s project management.

  8. [Carbon monoxide metabolism by photosynthetic bacteria]. Progress report

    SciTech Connect

    Not Available

    1989-12-31

    Research continued on the metabolism of carbon monoxide by Rhodospirillum rubrum. This report discusses progress on the activity, induction, inhibition, and spectroscopic analysis of the enzyme Carbon Monoxide Dehydrogenase. (CBS)

  9. (Regulation of teopene metabolism). Progress report. [Mentha piperita

    SciTech Connect

    Croteau, R.

    1985-01-01

    Progress in elucidating the biosynthesis of several monoterpenes in the peppermint is described. Tracer studies were performed to clarify metabolic pathways involved. Several growth regulators were screened for their influence on monoterpene composition and yield in peppermint and sage. (DT)

  10. Regulation of terpene metabolism. Progress report, 1983

    SciTech Connect

    Croteau, R.

    1986-01-01

    Studies on the metabolism of terpenes by peppermint (Menta piperita) are described. The studies describe the characterization of enzymes involved in the biosynthesis and catabolism of terpenes and the ultrastructure of the oil glands. 10 refs. (DT)

  11. Final Technical Progress Report NANOSTRUCTURED MAGNETIC MATERIALS

    SciTech Connect

    Charles M. Falco

    2012-09-13

    This report describes progress made during the final phase of our DOE-funded program on Nanostructured Magnetic Materials. This period was quite productive, resulting in the submission of three papers and presentation of three talks at international conferences and three seminars at research institutions. Our DOE-funded research efforts were directed toward studies of magnetism at surfaces and interfaces in high-quality, well-characterized materials prepared by Molecular Beam Epitaxy (MBE) and sputtering. We have an exceptionally well-equipped laboratory for these studies, with: Thin film preparation equipment; Characterization equipment; Equipment to study magnetic properties of surfaces and ultra-thin magnetic films and interfaces in multi-layers and superlattices.

  12. Progress in Metabolic Engineering of Saccharomyces cerevisiae

    PubMed Central

    Nevoigt, Elke

    2008-01-01

    Summary: The traditional use of the yeast Saccharomyces cerevisiae in alcoholic fermentation has, over time, resulted in substantial accumulated knowledge concerning genetics, physiology, and biochemistry as well as genetic engineering and fermentation technologies. S. cerevisiae has become a platform organism for developing metabolic engineering strategies, methods, and tools. The current review discusses the relevance of several engineering strategies, such as rational and inverse metabolic engineering, evolutionary engineering, and global transcription machinery engineering, in yeast strain improvement. It also summarizes existing tools for fine-tuning and regulating enzyme activities and thus metabolic pathways. Recent examples of yeast metabolic engineering for food, beverage, and industrial biotechnology (bioethanol and bulk and fine chemicals) follow. S. cerevisiae currently enjoys increasing popularity as a production organism in industrial (“white”) biotechnology due to its inherent tolerance of low pH values and high ethanol and inhibitor concentrations and its ability to grow anaerobically. Attention is paid to utilizing lignocellulosic biomass as a potential substrate. PMID:18772282

  13. Poultry waste digester. Final progress report

    SciTech Connect

    Shih, J.C.H.

    1983-01-01

    A simple and low-cost poultry waste digester (PWD) was constructed at North Carolina State University's Poultry Research Farm at Raleigh, N.C. The PWD system was designed to process a daily output of 600 kg of manure from 4000 caged laying hens. The system consisted of two digesters connected in series, a heating system, a hot water tank, and other metering equipment. The primary and secondary digesters were horizontal cylinders located partially below ground level. They were made of Red Mud plastic lining, supported in the insulated trenches, and covered with insulated roofs. The primary digester volume was 15 m/sup 3/ with an 8 m/sup 3/ liquid volume and a gas head-space above the liquid. The secondary digester volume was 30 m/sup 3/ with a 16 m/sup 3/ liquid volume. The temperature (50/sup 0/C) of the primary digester was maintained by the hot dilution water added with manure and a SolaRoll heating mat laid underneath the plastic lining. The design, operation, performance, energy balance, and economics of the digester are discussed and evaluated in this final progress report.

  14. Metabolic Reprograming of Mononuclear Phagocytes in Progressive Multiple Sclerosis

    PubMed Central

    Tannahill, Gillian Margaret; Iraci, Nunzio; Gaude, Edoardo; Frezza, Christian; Pluchino, Stefano

    2015-01-01

    Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system (CNS). Accumulation of brain damage in progressive MS is partly the result of mononuclear phagocytes (MPs) attacking myelin sheaths in the CNS. Although there is no cure yet for MS, significant advances have been made in the development of disease modifying agents. Unfortunately, most of these drugs fail to reverse established neurological deficits and can have adverse effects. Recent evidence suggests that MPs polarization is accompanied by profound metabolic changes, whereby pro-inflammatory MPs (M1) switch toward glycolysis, whereas anti-inflammatory MPs (M2) become more oxidative. It is therefore possible that reprograming MPs metabolism could affect their function and repress immune cell activation. This mini review describes the metabolic changes underpinning macrophages polarization and anticipates how metabolic re-education of MPs could be used for the treatment of MS. Key points: Inflammation in progressive MS is mediated primarily by MPs.Cell metabolism regulates the function of MPs.DMAs can re-educate the metabolism of MPs to promote healing. PMID:25814990

  15. [Regulation of terpene metabolism: Final report

    SciTech Connect

    Croteau, R.

    1991-12-31

    We have completed studies on the key pathways of monoterpene biosynthesis in sage and peppermint, and on biosynthetic enzymes. We have confirmed that monoterpene turnover does occur, have deciphered the function of this process in plants, delineated the essential features of the catabolic pathways for camphor and menthone, and initiated studies on the relevant enzymology. We have made a strong case, based on analytical, in vivo, and in vitro studies, that terpene accumulation (yield and composition) depends on the balance between biosynthetic and catabolic events, and provided supporting evidence that these processes are developmentally regulated and very closely associated with senescence (collapse) of the oil glands. We have demonstrated that foliar applied bioregulators influence terpene composition and yield, probably by a combination of effects in oil gland development and by more direct alteration of enzyme levels. These studies have provided a practical means for modifying terpene composition and yield and, moreover, have provided a powerful approach to studying developmental regulation in intact plants, explants and tissue culture systems. We have thus developed the fundamental background knowledge needed as well as the necessary experimental tools for studying the regulation of terpene metabolism.

  16. (Regulation of terpene metabolism: Final report)

    SciTech Connect

    Croteau, R.

    1991-01-01

    We have completed studies on the key pathways of monoterpene biosynthesis in sage and peppermint, and on biosynthetic enzymes. We have confirmed that monoterpene turnover does occur, have deciphered the function of this process in plants, delineated the essential features of the catabolic pathways for camphor and menthone, and initiated studies on the relevant enzymology. We have made a strong case, based on analytical, in vivo, and in vitro studies, that terpene accumulation (yield and composition) depends on the balance between biosynthetic and catabolic events, and provided supporting evidence that these processes are developmentally regulated and very closely associated with senescence (collapse) of the oil glands. We have demonstrated that foliar applied bioregulators influence terpene composition and yield, probably by a combination of effects in oil gland development and by more direct alteration of enzyme levels. These studies have provided a practical means for modifying terpene composition and yield and, moreover, have provided a powerful approach to studying developmental regulation in intact plants, explants and tissue culture systems. We have thus developed the fundamental background knowledge needed as well as the necessary experimental tools for studying the regulation of terpene metabolism.

  17. Final/Progress Report for Instrumentation Grant

    SciTech Connect

    1997-03-31

    The major piece of equipment was a Furnace Model 1000 used during the Nitrate to Ammonia and Ceramic (NAC) process to sinter the ceramic final product. NAC is a new technology to immobilize liquid radioactive waste simulants. The grant also funded related control and measuring equipment.

  18. Progress toward improved therapies for inborn errors of metabolism.

    PubMed

    Ginocchio, Virginia Maria; Brunetti-Pierri, Nicola

    2016-04-15

    Because of their prevalence, severity and lack of effective treatments, inborn errors of metabolism need novel and more effective therapeutic approaches. The opportunity for an early treatment coming from expanded newborn screening has made this need even more urgent. To meet this demand, a growing number of novel treatments are entering in the phase of clinical development. Strategies to overcome the detrimental consequences of the enzyme deficiencies responsible for inborn errors of metabolism have been focused on multiple fronts at the levels of the gene, RNA, protein and whole cell. These strategies have been accomplished using a wide spectrum of approaches ranging from small molecules to enzyme replacement therapy, cell and gene therapy. The applications of new technologies in the field of inborn errors of metabolism, such as genome editing, RNA interference and cell reprogramming, along with progress in pre-existing strategies, such as gene therapy or cell transplantation, have tremendous potential for clinical translation. PMID:26443595

  19. Metabolic, autophagic, and mitophagic activities in cancer initiation and progression.

    PubMed

    Hjelmeland, Anita; Zhang, Jianhua

    2016-04-01

    Cancer is a complex disease marked by uncontrolled cell growth and invasion. These processes are driven by the accumulation of genetic and epigenetic alterations that promote cancer initiation and progression. Contributing to genome changes are the regulation of oxidative stress and reactive species-induced damage to molecules and organelles. Redox regulation, metabolic plasticity, autophagy, and mitophagy play important and interactive roles in cancer hallmarks including sustained proliferation, activated invasion, and replicative immortality. However, the impact of these processes can differ depending on the signaling pathways altered in cancer, tumor type, tumor stage, and/or the differentiation state. Here, we highlight some of the representative studies on the impact of oxidative and nitrosative activities, mitochondrial bioenergetics, metabolism, and autophagy and mitophagy in the context of tumorigenesis. We discuss the implications of these processes for cellular activities in cancer for anti-cancer-based therapeutics. PMID:27372165

  20. Vitamin D, intermediary metabolism and prostate cancer tumor progression

    PubMed Central

    Wang, Wei-Lin W.; Tenniswood, Martin

    2014-01-01

    Epidemiological data have demonstrated an inverse association between serum vitamin D3 levels, cancer incidence and related mortality. However, the effects of vitamin D on prostate cancer biology and its utility for prevention of prostate cancer progression are not as well-defined. The data are often conflicting: some reports suggest that vitamin D3 induces apoptosis in androgen dependent prostate cancer cell lines, while others suggest that vitamin D3 only induces cell cycle arrest. Recent molecular studies have identified an extensive synergistic crosstalk between the vitamin D- and androgen-mediated mRNA and miRNA expression, adding an additional layer of post-transcriptional regulation to the known VDR- and AR-regulated gene activation. The Warburg effect, the inefficient metabolic pathway that converts glucose to lactate for rapid energy generation, is a phenomenon common to many different types of cancer. This process supports cell proliferation and promotes cancer progression via alteration of glucose, glutamine and lipid metabolism. Prostate cancer is a notable exception to this general process since the metabolic switch that occurs early during malignancy is the reverse of the Warburg effect. This “anti-Warburg effect” is due to the unique biology of normal prostate cells that harbor a truncated TCA cycle that is required to produce and secret citrate. In prostate cancer cells, the TCA cycle activity is restored and citrate oxidation is used to produce energy for cancer cell proliferation. 1,25(OH)2D3 and androgen together modulates the TCA cycle via transcriptional regulation of zinc transporters, suggesting that 1,25(OH)2D3 and androgen maintain normal prostate metabolism by blocking citrate oxidation. These data demonstrate the importance of androgens in the anti-proliferative effect of vitamin D in prostate cancer and highlight the importance of understanding the crosstalk between these two signaling pathways. PMID:24860512

  1. Vitamin D, intermediary metabolism and prostate cancer tumor progression.

    PubMed

    Wang, Wei-Lin W; Tenniswood, Martin

    2014-01-01

    Epidemiological data have demonstrated an inverse association between serum vitamin D3 levels, cancer incidence and related mortality. However, the effects of vitamin D on prostate cancer biology and its utility for prevention of prostate cancer progression are not as well-defined. The data are often conflicting: some reports suggest that vitamin D3 induces apoptosis in androgen dependent prostate cancer cell lines, while others suggest that vitamin D3 only induces cell cycle arrest. Recent molecular studies have identified an extensive synergistic crosstalk between the vitamin D- and androgen-mediated mRNA and miRNA expression, adding an additional layer of post-transcriptional regulation to the known VDR- and AR-regulated gene activation. The Warburg effect, the inefficient metabolic pathway that converts glucose to lactate for rapid energy generation, is a phenomenon common to many different types of cancer. This process supports cell proliferation and promotes cancer progression via alteration of glucose, glutamine and lipid metabolism. Prostate cancer is a notable exception to this general process since the metabolic switch that occurs early during malignancy is the reverse of the Warburg effect. This "anti-Warburg effect" is due to the unique biology of normal prostate cells that harbor a truncated TCA cycle that is required to produce and secret citrate. In prostate cancer cells, the TCA cycle activity is restored and citrate oxidation is used to produce energy for cancer cell proliferation. 1,25(OH)2D3 and androgen together modulates the TCA cycle via transcriptional regulation of zinc transporters, suggesting that 1,25(OH)2D3 and androgen maintain normal prostate metabolism by blocking citrate oxidation. These data demonstrate the importance of androgens in the anti-proliferative effect of vitamin D in prostate cancer and highlight the importance of understanding the crosstalk between these two signaling pathways. PMID:24860512

  2. Metabolic Syndrome and Periodontal Disease Progression in Men.

    PubMed

    Kaye, E K; Chen, N; Cabral, H J; Vokonas, P; Garcia, R I

    2016-07-01

    Metabolic syndrome, a cluster of 3 or more risk factors for cardiovascular disease, is associated with periodontal disease, but few studies have been prospective in design. This study's aim was to determine whether metabolic syndrome predicts tooth loss and worsening of periodontal disease in a cohort of 760 men in the Department of Veterans Affairs Dental Longitudinal Study and Normative Aging Study who were followed up to 33 y from 1981 to 2013. Systolic and diastolic blood pressures were measured with a standard mercury sphygmomanometer. Waist circumference was measured in units of 0.1 cm following a normal expiration. Fasting blood samples were measured in duplicate for glucose, triglyceride, and high-density lipoprotein. Calibrated periodontists served as dental examiners. Periodontal outcome events on each tooth were defined as progression to predefined threshold levels of probing pocket depth (≥5 mm), clinical attachment loss (≥5 mm), mobility (≥0.5 mm), and alveolar bone loss (≥40% of the distance from the cementoenamel junction to the root apex, on radiographs). Hazards ratios (95% confidence intervals) of tooth loss or a periodontitis event were estimated from tooth-level extended Cox proportional hazards regression models that accounted for clustering of teeth within individuals and used time-dependent status of metabolic syndrome. Covariates included age, education, smoking status, plaque level, and initial level of the appropriate periodontal disease measure. Metabolic syndrome as defined by the International Diabetes Federation increased the hazards of tooth loss (1.39; 1.08 to 1.79), pocket depth ≥5 mm (1.37; 1.14 to 1.65), clinical attachment loss ≥5 mm (1.19; 1.00 to 1.41), alveolar bone loss ≥40% (1.25; 1.00 to 1.56), and tooth mobility ≥0.5 mm (1.43; 1.07 to 1.89). The number of positive metabolic syndrome conditions was also associated with each of these outcomes. These findings suggest that the metabolic disturbances that

  3. Comparative Analysis of Yeast Metabolic Network Models Highlights Progress, Opportunities for Metabolic Reconstruction.

    PubMed

    Heavner, Benjamin D; Price, Nathan D

    2015-11-01

    We have compared 12 genome-scale models of the Saccharomyces cerevisiae metabolic network published since 2003 to evaluate progress in reconstruction of the yeast metabolic network. We compared the genomic coverage, overlap of annotated metabolites, predictive ability for single gene essentiality with a selection of model parameters, and biomass production predictions in simulated nutrient-limited conditions. We have also compared pairwise gene knockout essentiality predictions for 10 of these models. We found that varying approaches to model scope and annotation reflected the involvement of multiple research groups in model development; that single-gene essentiality predictions were affected by simulated medium, objective function, and the reference list of essential genes; and that predictive ability for single-gene essentiality did not correlate well with predictive ability for our reference list of synthetic lethal gene interactions (R = 0.159). We conclude that the reconstruction of the yeast metabolic network is indeed gradually improving through the iterative process of model development, and there remains great opportunity for advancing our understanding of biology through continued efforts to reconstruct the full biochemical reaction network that constitutes yeast metabolism. Additionally, we suggest that there is opportunity for refining the process of deriving a metabolic model from a metabolic network reconstruction to facilitate mechanistic investigation and discovery. This comparative study lays the groundwork for developing improved tools and formalized methods to quantitatively assess metabolic network reconstructions independently of any particular model application, which will facilitate ongoing efforts to advance our understanding of the relationship between genotype and cellular phenotype. PMID:26566239

  4. Comparative Analysis of Yeast Metabolic Network Models Highlights Progress, Opportunities for Metabolic Reconstruction

    PubMed Central

    Heavner, Benjamin D.; Price, Nathan D.

    2015-01-01

    We have compared 12 genome-scale models of the Saccharomyces cerevisiae metabolic network published since 2003 to evaluate progress in reconstruction of the yeast metabolic network. We compared the genomic coverage, overlap of annotated metabolites, predictive ability for single gene essentiality with a selection of model parameters, and biomass production predictions in simulated nutrient-limited conditions. We have also compared pairwise gene knockout essentiality predictions for 10 of these models. We found that varying approaches to model scope and annotation reflected the involvement of multiple research groups in model development; that single-gene essentiality predictions were affected by simulated medium, objective function, and the reference list of essential genes; and that predictive ability for single-gene essentiality did not correlate well with predictive ability for our reference list of synthetic lethal gene interactions (R = 0.159). We conclude that the reconstruction of the yeast metabolic network is indeed gradually improving through the iterative process of model development, and there remains great opportunity for advancing our understanding of biology through continued efforts to reconstruct the full biochemical reaction network that constitutes yeast metabolism. Additionally, we suggest that there is opportunity for refining the process of deriving a metabolic model from a metabolic network reconstruction to facilitate mechanistic investigation and discovery. This comparative study lays the groundwork for developing improved tools and formalized methods to quantitatively assess metabolic network reconstructions independently of any particular model application, which will facilitate ongoing efforts to advance our understanding of the relationship between genotype and cellular phenotype. PMID:26566239

  5. [Regulation of terpene metabolism]. Annual progress report, March 15, 1988--March 14, 1989

    SciTech Connect

    Croteau, R.

    1989-12-31

    Progress in understanding of the metabolism of monoterpenes by peppermint and spearmint is recorded including the actions of two key enzymes, geranyl pyrophosphate:limonene cyclase and a UDP-glucose dependent glucosyl transferase; concerning the ultrastructure of oil gland senescence; enzyme subcellular localization; regulation of metabolism; and tissue culture systems.

  6. Kidney cancer progression linked to shifts in tumor metabolism

    Cancer.gov

    Investigators in The Cancer Genome Atlas Research Network have uncovered a connection between how tumor cells use energy from metabolic processes and the aggressiveness of the most common form of kidney cancer, clear cell renal cell carcinoma.

  7. Obesity and cancer progression: is there a role of fatty acid metabolism?

    PubMed

    Balaban, Seher; Lee, Lisa S; Schreuder, Mark; Hoy, Andrew J

    2015-01-01

    Currently, there is renewed interest in elucidating the metabolic characteristics of cancer and how these characteristics may be exploited as therapeutic targets. Much attention has centered on glucose, glutamine and de novo lipogenesis, yet the metabolism of fatty acids that arise from extracellular, as well as intracellular, stores as triacylglycerol has received much less attention. This review focuses on the key pathways of fatty acid metabolism, including uptake, esterification, lipolysis, and mitochondrial oxidation, and how the regulators of these pathways are altered in cancer. Additionally, we discuss the potential link that fatty acid metabolism may serve between obesity and changes in cancer progression. PMID:25866768

  8. Obesity and Cancer Progression: Is There a Role of Fatty Acid Metabolism?

    PubMed Central

    Balaban, Seher; Lee, Lisa S.; Schreuder, Mark; Hoy, Andrew J.

    2015-01-01

    Currently, there is renewed interest in elucidating the metabolic characteristics of cancer and how these characteristics may be exploited as therapeutic targets. Much attention has centered on glucose, glutamine and de novo lipogenesis, yet the metabolism of fatty acids that arise from extracellular, as well as intracellular, stores as triacylglycerol has received much less attention. This review focuses on the key pathways of fatty acid metabolism, including uptake, esterification, lipolysis, and mitochondrial oxidation, and how the regulators of these pathways are altered in cancer. Additionally, we discuss the potential link that fatty acid metabolism may serve between obesity and changes in cancer progression. PMID:25866768

  9. Studies in iodine metabolism. Progress report, 1982-1983

    SciTech Connect

    Van Middlesworth, L.

    1983-01-01

    Research progress is reported for the period 1982 to 1983 in the following areas: (1) monitoring of animal thyroids for /sup 129/I, /sup 125/I, /sup 131/I, /sup 226/Ra, and /sup 228/Ra; and (2) neonatal hypo-l thyroidism in laboratory rats. (ACR)

  10. (Regulation of terpene metabolism). Progress report. [Mentha piperita

    SciTech Connect

    Croteau, R.

    1986-01-01

    Studies on the regulation of monoterpene metabolism in M. piperita were conducted. All of the steps from the acyclic precursor geranyl pyrophosphate to the various menthol isomers have been demonstrated. The first intermediate to accumulate in vivo is d-pulegone. The emphasis has been on the demonstration, partial purification and characterization of the relevant enzymes in the pathway. The studies on the isopiperitenol dehydrogenase and isopiperitenone isomerase have been completed. We are not studying the endocyclic double-bond reductase (NADPH-dependent) and, based on substrate specificity studies and the previously demonstrated isomerization of cis- isopulegone to pulegone, are now virtually convinced that the major pathway to menthol(s) in peppermint involves reduction of isopiperitenone to isopulegone and isomerication of isopulegone to pulegone. 16 refs., 1 fig.

  11. BCAT1 expression associates with ovarian cancer progression: possible implications in altered disease metabolism

    PubMed Central

    Wang, Zhi-Qiang; Faddaoui, Adnen; Bachvarova, Magdalena; Plante, Marie; Gregoire, Jean; Renaud, Marie-Claude; Sebastianelli, Alexandra; Guillemette, Chantal; Gobeil, Stéphane; Macdonald, Elizabeth; Vanderhyden, Barbara; Bachvarov, Dimcho

    2015-01-01

    Previously, we have identified the branched chain amino-acid transaminase 1 (BCAT1) gene as notably hypomethylated in low-malignant potential (LMP) and high-grade (HG) serous epithelial ovarian tumors, compared to normal ovarian tissues. Here we show that BCAT1 is strongly overexpressed in both LMP and HG serous epithelial ovarian tumors, which probably correlates with its hypomethylated status. Knockdown of the BCAT1 expression in epithelial ovarian cancer (EOC) cells led to sharp decrease of cell proliferation, migration and invasion and inhibited cell cycle progression. BCAT1 silencing was associated with the suppression of numerous genes and pathways known previously to be implicated in ovarian tumorigenesis, and the induction of some tumor suppressor genes (TSGs). Moreover, BCAT1 suppression resulted in downregulation of numerous genes implicated in lipid production and protein synthesis, suggesting its important role in controlling EOC metabolism. Further metabolomic analyses were indicative for significant depletion of most amino acids and different phospho- and sphingolipids following BCAT1 knockdown. Finally, BCAT1 suppression led to significantly prolonged survival time in xenograft model of advanced peritoneal EOC. Taken together, our findings provide new insights about the functional role of BCAT1 in ovarian carcinogenesis and identify this transaminase as a novel EOC biomarker and putative EOC therapeutic target. PMID:26372729

  12. Mitochondrial-associated metabolic disorders: foundations, pathologies and recent progress

    PubMed Central

    2013-01-01

    Research in the last decade has revolutionized the way in which we view mitochondria. Mitochondria are no longer viewed solely as cellular powerhouses; rather, mitochondria are now understood to be vibrant, mobile structures, constantly undergoing fusion and fission, and engaging in intimate interactions with other cellular compartments and structures. Findings have implicated mitochondria in a wide variety of cellular processes and molecular interactions, such as calcium buffering, lipid flux, and intracellular signaling. As such, it does not come as a surprise that an increasing number of human pathologies have been associated with functional defects in mitochondria. The difficulty in understanding and treating human pathologies caused by mitochondrial dysfunction arises from the complex relationships between mitochondria and other cellular processes, as well as the genetic background of such diseases. This review attempts to provide a summary of the background knowledge and recent developments in mitochondrial processes relating to mitochondrial-associated metabolic diseases arising from defects or deficiencies in mitochondrial function, as well as insights into current and future avenues for investigation. PMID:24499129

  13. Newborn screening of metabolic disorders: recent progress and future developments.

    PubMed

    Rinaldo, Piero; Lim, James S; Tortorelli, Silvia; Gavrilov, Dimitar; Matern, Dietrich

    2008-01-01

    Tandem mass spectrometry has been the main driver behind a significant expansion in newborn screening programs. The ability to detect more than 40 conditions by a single test underscores the need to better understand the clinical and laboratory characteristics of the conditions being tested, and the complexity of pattern recognition and differential diagnoses of one or more elevated markers. The panel of conditions recommended by the American College of Medical Genetics, including 20 primary conditions and 22 secondary targets that are detectable by tandem mass spectrometry has been adopted as the standard of care in the vast majority of US states. The evolution of newborn screening is far from being idle as a large number of infectious, genetic, and metabolic conditions are currently under investigation at variable stages of test development and clinical validation. In the US, a formal process with oversight by the Advisory Committee on Heritable Disorders and Genetic Diseases in Newborns and Children has been established for nomination and evidence-based review of new candidate conditions. If approved, these conditions could be added to the uniform panel and consequently pave the way to large scale implementation. PMID:18626194

  14. Classical and Non-Classical Roles for Pre-Receptor Control of DHT Metabolism in Prostate Cancer Progression.

    PubMed

    Zhang, Ailin; Zhang, Jiawei; Plymate, Stephen; Mostaghel, Elahe A

    2016-04-01

    Androgens play an important role in prostate cancer (PCa) development and progression. Accordingly, androgen deprivation therapy remains the front-line treatment for locally recurrent or advanced PCa, but patients eventually relapse with the lethal form of the disease termed castration resistant PCa (CRPC). Importantly, castration does not eliminate androgens from the prostate tumor microenvironment which is characterized by elevated tissue androgens that are well within the range capable of activating the androgen receptor (AR). In this mini-review, we discuss emerging data that suggest a role for the enzymes mediating pre-receptor control of dihydrotestosterone (DHT) metabolism, including AKR1C2, HSD17B6, HSD17B10, and the UGT family members UGT2B15 and UGT2B17, in controlling intratumoral androgen levels, and thereby influencing PCa progression. We review the expression of steroidogenic enzymes involved in this pathway in primary PCa and CRPC, the activity and regulation of these enzymes in PCa experimental models, and the impact of genetic variation in genes mediating pre-receptor DHT metabolism on PCa risk. Finally, we discuss recent data that suggests several of these enzymes may also play an unrecognized role in CRPC progression separate from their role in androgen inactivation. PMID:26797685

  15. Extra focal convective suppressing solar collector. Final technical progress report

    SciTech Connect

    1996-05-01

    This progress report describes work done on the Extra Focal Convective Suppressing Solar Collector. The topics of the report include sensor refinement for the tracking electronics, tracking controller refinement, system optics evaluation, absorber system material evaluation and performance, tracking hardware evaluation and refinement, and full scale prototype construction and testing.

  16. Role of abnormal lipid metabolism in development, progression, diagnosis and therapy of pancreatic cancer

    PubMed Central

    Swierczynski, Julian; Hebanowska, Areta; Sledzinski, Tomasz

    2014-01-01

    There is growing evidence that metabolic alterations play an important role in cancer development and progression. The metabolism of cancer cells is reprogrammed in order to support their rapid proliferation. Elevated fatty acid synthesis is one of the most important aberrations of cancer cell metabolism. An enhancement of fatty acids synthesis is required both for carcinogenesis and cancer cell survival, as inhibition of key lipogenic enzymes slows down the growth of tumor cells and impairs their survival. Based on the data that serum fatty acid synthase (FASN), also known as oncoantigen 519, is elevated in patients with certain types of cancer, its serum level was proposed as a marker of neoplasia. This review aims to demonstrate the changes in lipid metabolism and other metabolic processes associated with lipid metabolism in pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic neoplasm, characterized by high mortality. We also addressed the influence of some oncogenic factors and tumor suppressors on pancreatic cancer cell metabolism. Additionally the review discusses the potential role of elevated lipid synthesis in diagnosis and treatment of pancreatic cancer. In particular, FASN is a viable candidate for indicator of pathologic state, marker of neoplasia, as well as, pharmacological treatment target in pancreatic cancer. Recent research showed that, in addition to lipogenesis, certain cancer cells can use fatty acids from circulation, derived from diet (chylomicrons), synthesized in liver, or released from adipose tissue for their growth. Thus, the interactions between de novo lipogenesis and uptake of fatty acids from circulation by PDAC cells require further investigation. PMID:24605027

  17. The Role of Mitochondria in Cancer Induction, Progression and Changes in Metabolism.

    PubMed

    Rogalinska, Malgorzata

    2016-01-01

    Mitochondria play important roles as energetic centers. Mutations in mitochondrial DNA (mtDNA) were found in several diseases, including cancers. Studies on cytoplasmic hybrids (cybrids) confirm that directed mutation introduced into mtDNA could be a reason for cancer induction. Mitochondria could also be a factor linking cancer transformation and progression. The importance of mitochondria in cancer also confirms their involvement in the resistance to treatment. Resistance to treatment of cancer cells can frequently be a reason for glycolysis acceleration. It could be explained by cancer cells' high proliferation index and high energy request. The involvement of mitochondria in metabolic disturbances of several metabolic diseases, including cancers, was reported. These data confirm that cancer induction, as well as cancer progression, could have metabolic roots. The aberrant products observed in prostate cells involved in the Krebs cycle could promote cancer progression. These multiple relationships between alterations on a genetic level translated into disturbances in cellular metabolism and their potential relation with epigenetic control of gene expression make cancerogenesis more complicated and prognoses' success in studies on cancer etiology more distant in time. PMID:26471969

  18. Nuclear Physics Laboratory, University of Colorado, Final Progress Report

    SciTech Connect

    Kinney, E.R., ed.

    2004-05-12

    OAK-B135 The results and progress of research funded by DOE grant number DOE-FG03-95ER40913 at the University of Colorado at Boulder is described. Includes work performed at the HERMES experiment at DESY to study the quark structure of the nucleon and the hadronization process in nuclei, as well as hadronic reactions studied at LAMPF, KEK, and Fermilab.

  19. Cerebral glucose metabolism in corticobasal degeneration comparison with progressive supranuclear palsy using statistical mapping analysis.

    PubMed

    Juh, Rahyeong; Pae, Chi-Un; Kim, Tae-Suk; Lee, Chang-Uk; Choe, Boyoung; Suh, Taesuk

    This study measured the cerebral glucose metabolism in patients suffering from corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). The aim was to determine if there is a different metabolic pattern using (18)F-labeled 2-deoxyglucose ((18)F-FDG) positron emission tomography (PET). The regional cerebral glucose metabolism was examined in 8 patients diagnosed clinically with CBD (mean age 69.6 +/- 7.8 years; male/female: 5/3), 8 patients with probable PSP (mean age 67.8 +/- 4.5 years; male/female: 4/4) and 22 healthy controls. The regional cerebral glucose metabolism between the three groups was compared using statistical parametric mapping (SPM) with a voxel-by-voxel approach (p < 0.001, 200-voxel level). Compared with the normal controls, asymmetry in the regional glucose metabolism was observed in the parietal, frontal and cingulate in the CBD patients. In the PSP patients, the glucose metabolism was lower in the orbitofrontal, middle frontal, cingulate, thalamus and mid-brain than their age matched normal controls. A comparison of the two patient groups demonstrated relative hypometabolism in the thalamus, the mid-brain in the PSP patients and the parietal lobe in CBD patients. These results suggest that when making a differential diagnosis of CBD and PSP, voxel-based analysis of the (18)F-FDG PET images using a SPM might be a useful tool in clinical examinations. PMID:15936506

  20. [Research Progress on role of Abnormal Tryptophan Metabolism in Immune Thrombocytopenia].

    PubMed

    Li, Zhao-Jian; Liu, Xiao-Qian; Xu, Jun-Qing; Chu, Xiao-Xia

    2015-12-01

    Immune thrombocytopenia (ITP) is a common acquired autoimmune hematological disorders. Platelet autoantibodies lead to the decrease of platelet production and (or) increase of its destruction. The latest researches showed that the abnormal tryptophan metabolism mediated by indoleamine-2, 3-dioxygenase(IDO) is related with the pathogenesis of ITP. The patients with ITP show less expression of IDO, reduction of Treg cells and increase of autoreactive T cells and autoantibodies. CTLA-4-Ig can improve the expression of IDO in the patients with ITP, which also can inhibit the proliferation and activation of self-reactive T cells. Thus, clarifying the abnormal tryptophan metabolism mediated by IDO may provide a new idea for improving the understand of the pathogenesis and treatment of ITP. This review focuses on reasearch progress of the tryptophan metabolism mediated by IDO and ITP. PMID:26708916

  1. Repeat cross-sectional data on the progression of the metabolic syndrome in Ossabaw miniature swine

    PubMed Central

    McKenney-Drake, Mikaela L.; Rodenbeck, Stacey D.; Owen, Meredith K.; Schultz, Kyle A.; Alloosh, Mouhamad; Tune, Johnathan D.; Sturek, Michael

    2016-01-01

    Ossabaw miniature swine were fed an excess calorie, atherogenic diet for 6, 9, or 12 months. Increased body weight, hypertension, and increased plasma cholesterol and triglycerides are described in Table 1. For more detailed interpretations and conclusions about the data, see our associated research study, “Biphasic alterations in coronary smooth muscle Ca2+ regulation during coronary artery disease progression in metabolic syndrome” McKenney-Drake, et al. (2016) [1]. PMID:27158656

  2. Repeat cross-sectional data on the progression of the metabolic syndrome in Ossabaw miniature swine.

    PubMed

    McKenney-Drake, Mikaela L; Rodenbeck, Stacey D; Owen, Meredith K; Schultz, Kyle A; Alloosh, Mouhamad; Tune, Johnathan D; Sturek, Michael

    2016-06-01

    Ossabaw miniature swine were fed an excess calorie, atherogenic diet for 6, 9, or 12 months. Increased body weight, hypertension, and increased plasma cholesterol and triglycerides are described in Table 1. For more detailed interpretations and conclusions about the data, see our associated research study, "Biphasic alterations in coronary smooth muscle Ca(2+) regulation during coronary artery disease progression in metabolic syndrome" McKenney-Drake, et al. (2016) [1]. PMID:27158656

  3. Final Progress Report for Ionospheric Dusty Plasma In the Laboratory [Smokey Plasma

    SciTech Connect

    Robertson, Scott

    2010-09-28

    “Ionospheric Dusty Plasma in the Laboratory” is a research project with the purpose of finding and reproducing the characteristics of plasma in the polar mesosphere that is unusually cold (down to 140 K) and contains nanometer-sized dust particles. This final progress report summarizes results from four years of effort that include a final year with a no-cost extension.

  4. Nuclear research with the electromagnetic probe. Final progress report

    SciTech Connect

    Meziani, Z.E.

    1994-10-01

    This is the final report on the research carried at Stanford University under contract DE-FG03-88ER40439. All the work accomplished under this grant is reported in the publications listed as part of the Principal Investigator bibliography at the end of this report. In the last few years our research was directed at some of the forefront questions in nuclear physics. We investigated the nuclear medium effects on the intrinsic properties of bound nucleons, specifically the ectromagnetic form factors. For these studies we performed a number of specialized electron scattering experiments with specific sensitivity to nuclear medium effects. At the next level of structure, elementary constituents of matter are quarks and gluons. Defining the energy regime where the quark-gluon description of nuclear systems becomes more relevant than the nucleon-meson description is of great importance in thoroughly understanding the nuclear structure. To explore this transition region, we studied the scaling region in the disintegration of the deuteron, the simplest nuclear system with high energy photons. Finally we focused on the investigation of the nucleon internal spin structure along with the test of the Bjoerken sum rule a fundamental sum rule of QCD.

  5. Final Progress Report for FG02-89ER14030

    SciTech Connect

    Hanson, Maureen R

    2011-10-26

    have provided more information on stromule formation and function and the actin-myosin machinery that mediates the intracellular trafficking that is required for photosynthesis and metabolism to operate efficiently within the plant cell.

  6. 1993 annual final progress report: July 1992 through June 1993

    SciTech Connect

    Rohatgi, A.; Crotty, G.; Chen, Z.; Sana, P.; Salami, J.; Doolittle, A.; Pang, A.; Pham, T.

    1994-11-01

    This is the first annual report since the Inauguration of the University Center of Excellence for Photovoltaics Research and Development (UCEP) at Georgia Tech. The essential objective of the Center is to improve the fundamental understanding of the science and technology of advanced PV devices and materials, to provide training and enrich the educational experience of students in the field, and to increase US competitiveness by providing guidelines to industry and DOE for achieving cost-effective and high efficiency PV devices. These objectives are to be accomplished through a combination of research and education. This report summarizes the technical accomplishments, including modeling, processing, and characterization of cast multicrystalline silicon solar cells; use of modeling and PCD measurements to develop a road map for progressing toward 20% multicrystalline and 25% single crystalline cells; the development of a novel PECVD SiN/SiO{sub 2} AR coating that also provides good surface passivation; PECVD deposited SiO{sub 2} films with record low S and D{sub it} at the SiO{sub 2}/Si interface; and educational activities and accomplishments.

  7. Development of a polystyrene insulation system. Final technical progress report

    SciTech Connect

    Rupert, J.G.

    1984-09-20

    An adhesive coating system for loose fill polystyrene materials was developed as a product primarily for retrofit insulation of residential buildings that would neither shrink nor settle. Several problems with the coated system including flammability and shrinkage led us to consider an alternative system in which an expanded rock product called perlite was considered as an alternative to polystyrene. The primary problems with perlite are that it is very expensive and the coated structure is extremely brittle. A very attractive commercial market for retrofit insulation using either polystyrene beads or shredded polystyrene was identified. Specifically, it was demonstrated that commercial cement block buildings can be reinsulated by filling the cores of the cement blocks with a payback period of three years. With additional development, it appears that the payback period can be reduced to 2 years at present natural gas prices. The potential market for a commercial system of this kind was analyzed and determined to be on the order of ten billion dollars nationally. The estimated potential energy savings are on order of one quad. At this time, the system is being redesigned to handle commercial buildings which have areas on the order of several hundred thousand square feet. Test marketing of the present system is in progress.

  8. Verification of Steelmaking Slags Iron Content Final Technical Progress Report

    SciTech Connect

    J.Y. Hwang

    2006-10-04

    The steel industry in the United States generates about 30 million tons of by-products each year, including 6 million tons of desulfurization and BOF/BOP slag. The recycling of BF (blast furnace) slag has made significant progress in past years with much of the material being utilized as construction aggregate and in cementitious applications. However, the recycling of desulfurization and BOF/BOP slags still faces many technical, economic, and environmental challenges. Previous efforts have focused on in-plant recycling of the by-products, achieving only limited success. As a result, large amounts of by-products of various qualities have been stockpiled at steel mills or disposed into landfills. After more than 50 years of stockpiling and landfilling, available mill site space has diminished and environmental constraints have increased. The prospect of conventionally landfilling of the material is a high cost option, a waste of true national resources, and an eternal material liability issue. The research effort has demonstrated that major inroads have been made in establishing the viability of recycling and reuse of the steelmaking slags. The research identified key components in the slags, developed technologies to separate the iron units and produce marketable products from the separation processes. Three products are generated from the technology developed in this research, including a high grade iron product containing about 90%Fe, a medium grade iron product containing about 60% Fe, and a low grade iron product containing less than 10% Fe. The high grade iron product contains primarily metallic iron and can be marketed as a replacement of pig iron or DRI (Direct Reduced Iron) for steel mills. The medium grade iron product contains both iron oxide and metallic iron and can be utilized as a substitute for the iron ore in the blast furnace. The low grade iron product is rich in calcium, magnesium and iron oxides and silicates. It has a sufficient lime value and

  9. Targeting metabolic flexibility by simultaneously inhibiting respiratory complex I and lactate generation retards melanoma progression

    PubMed Central

    Chaube, Balkrishna; Malvi, Parmanand; Singh, Shivendra Vikram; Mohammad, Naoshad; Meena, Avtar Singh; Bhat, Manoj Kumar

    2015-01-01

    Melanoma is a largely incurable skin malignancy owing to the underlying molecular and metabolic heterogeneity confounded by the development of resistance. Cancer cells have metabolic flexibility in choosing either oxidative phosphorylation (OXPHOS) or glycolysis for ATP generation depending upon the nutrient availability in tumor microenvironment. In this study, we investigated the involvement of respiratory complex I and lactate dehydrogenase (LDH) in melanoma progression. We show that inhibition of complex I by metformin promotes melanoma growth in mice via elevating lactate and VEGF levels. In contrast, it leads to the growth arrest in vitro because of enhanced extracellular acidification as a result of increased glycolysis. Inhibition of LDH or lactate generation causes decrease in glycolysis with concomitant growth arrest both in vitro and in vivo. Blocking lactate generation in metformin-treated melanoma cells results in diminished cell proliferation and tumor progression in mice. Interestingly, inhibition of either LDH or complex I alone does not induce apoptosis, whereas inhibiting both together causes depletion in cellular ATP pool resulting in metabolic catastrophe induced apoptosis. Overall, our study suggests that LDH and complex I play distinct roles in regulating glycolysis and cell proliferation. Inhibition of these two augments synthetic lethality in melanoma. PMID:26484566

  10. Microbial Regulation of Glucose Metabolism and Cell-Cycle Progression in Mammalian Colonocytes

    PubMed Central

    Donohoe, Dallas R.; Wali, Aminah; Brylawski, Bruna P.; Bultman, Scott J.

    2012-01-01

    A prodigious number of microbes inhabit the human body, especially in the lumen of the gastrointestinal (GI) tract, yet our knowledge of how they regulate metabolic pathways within our cells is rather limited. To investigate the role of microbiota in host energy metabolism, we analyzed ATP levels and AMPK phosphorylation in tissues isolated from germfree and conventionally-raised C57BL/6 mice. These experiments demonstrated that microbiota are required for energy homeostasis in the proximal colon to a greater extent than other segments of the GI tract that also harbor high densities of bacteria. This tissue-specific effect is consistent with colonocytes utilizing bacterially-produced butyrate as their primary energy source, whereas most other cell types utilize glucose. However, it was surprising that glucose did not compensate for butyrate deficiency. We measured a 3.5-fold increase in glucose uptake in germfree colonocytes. However, 13C-glucose metabolic-flux experiments and biochemical assays demonstrated that they shifted their glucose metabolism away from mitochondrial oxidation/CO2 production and toward increased glycolysis/lactate production, which does not yield enough ATPs to compensate. The mechanism responsible for this metabolic shift is diminished pyruvate dehydrogenase (PDH) levels and activity. Consistent with perturbed PDH function, the addition of butyrate, but not glucose, to germfree colonocytes ex vivo stimulated oxidative metabolism. As a result of this energetic defect, germfree colonocytes exhibited a partial block in the G1-to-S-phase transition that was rescued by a butyrate-fortified diet. These data reveal a mechanism by which microbiota regulate glucose utilization to influence energy homeostasis and cell-cycle progression of mammalian host cells. PMID:23029553

  11. Brain metabolic maps in Mild Cognitive Impairment predict heterogeneity of progression to dementia

    PubMed Central

    Cerami, Chiara; Della Rosa, Pasquale Anthony; Magnani, Giuseppe; Santangelo, Roberto; Marcone, Alessandra; Cappa, Stefano F.; Perani, Daniela

    2014-01-01

    [18F]FDG-PET imaging has been recognized as a crucial diagnostic marker in Mild Cognitive Impairment (MCI), supporting the presence or the exclusion of Alzheimer's Disease (AD) pathology. A clinical heterogeneity, however, underlies MCI definition. In this study, we aimed to evaluate the predictive role of single-subject voxel-based maps of [18F]FDG distribution generated through statistical parametric mapping (SPM) in the progression to different dementia subtypes in a sample of 45 MCI. Their scans were compared to a large normal reference dataset developed and validated for comparison at single-subject level. Additionally, Aβ42 and Tau CSF values were available in 34 MCI subjects. Clinical follow-up (mean 28.5 ± 7.8 months) assessed subsequent progression to AD or non-AD dementias. The SPM analysis showed: 1) normal brain metabolism in 14 MCI cases, none of them progressing to dementia; 2) the typical temporo-parietal pattern suggestive for prodromal AD in 15 cases, 11 of them progressing to AD; 3) brain hypometabolism suggestive of frontotemporal lobar degeneration (FTLD) subtypes in 7 and dementia with Lewy bodies (DLB) in 2 subjects (all fulfilled FTLD or DLB clinical criteria at follow-up); and 4) 7 MCI cases showed a selective unilateral or bilateral temporo-medial hypometabolism without the typical AD pattern, and they all remained stable. In our sample, objective voxel-based analysis of [18F]FDG-PET scans showed high predictive prognostic value, by identifying either normal brain metabolism or hypometabolic patterns suggestive of different underlying pathologies, as confirmed by progression at follow-up. These data support the potential usefulness of this SPM [18F]FDG PET analysis in the early dementia diagnosis and for improving subject selection in clinical trials based on MCI definition. PMID:25610780

  12. Altered Metabolic Homeostasis in Amyotrophic Lateral Sclerosis: Mechanisms of Energy Imbalance and Contribution to Disease Progression.

    PubMed

    Ioannides, Zara A; Ngo, Shyuan T; Henderson, Robert D; McCombe, Pamela A; Steyn, Frederik J

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the death of motor neurones, which leads to paralysis and death in an average of 3 years following diagnosis. The cause of ALS is unknown, but there is substantial evidence that metabolic factors, including nutritional state and body weight, affect disease progression and survival. This review provides an overview of the characteristics of metabolic dysregulation in ALS focusing on mechanisms that lead to disrupted energy supply (at a whole-body and cellular level) and altered energy expenditure. We discuss how a decrease in energy supply occurs in parallel with an increase in energy demand and leads to a state of chronic energy deficit which has a negative impact on disease outcome in ALS. We conclude by presenting potential and tested strategies to compensate for, or correct this energy imbalance, and speculate on promising areas for further research. PMID:27400276

  13. Progress and Challenges in Developing Metabolic Footprints from Diet in Human Gut Microbial Cometabolism12

    PubMed Central

    Duffy, Linda C; Raiten, Daniel J; Hubbard, Van S; Starke-Reed, Pamela

    2015-01-01

    Homo sapiens harbor trillions of microbes, whose microbial metagenome (collective genome of a microbial community) using omic validation interrogation tools is estimated to be at least 100-fold that of human cells, which comprise 23,000 genes. This article highlights some of the current progress and open questions in nutrition-related areas of microbiome research. It also underscores the metabolic capabilities of microbial fermentation on nutritional substrates that require further mechanistic understanding and systems biology approaches of studying functional interactions between diet composition, gut microbiota, and host metabolism. Questions surrounding bacterial fermentation and degradation of dietary constituents (particularly by Firmicutes and Bacteroidetes) and deciphering how microbial encoding of enzymes and derived metabolites affect recovery of dietary energy by the host are more complex than previously thought. Moreover, it is essential to understand to what extent the intestinal microbiota is subject to dietary control and to integrate these data with functional metabolic signatures and biomarkers. Many lines of research have demonstrated the significant role of the gut microbiota in human physiology and disease. Probiotic and prebiotic products are proliferating in the market in response to consumer demand, and the science and technology around these products are progressing rapidly. With high-throughput molecular technologies driving the science, studying the bidirectional interactions of host-microbial cometabolism, epithelial cell maturation, shaping of innate immune development, normal vs. dysfunctional nutrient absorption and processing, and the complex signaling pathways involved is now possible. Substantiating the safety and mechanisms of action of probiotic/prebiotic formulations is critical. Beneficial modulation of the human microbiota by using these nutritional and biotherapeutic strategies holds considerable promise as next

  14. Progress and challenges in developing metabolic footprints from diet in human gut microbial cometabolism.

    PubMed

    Duffy, Linda C; Raiten, Daniel J; Hubbard, Van S; Starke-Reed, Pamela

    2015-05-01

    Homo sapiens harbor trillions of microbes, whose microbial metagenome (collective genome of a microbial community) using omic validation interrogation tools is estimated to be at least 100-fold that of human cells, which comprise 23,000 genes. This article highlights some of the current progress and open questions in nutrition-related areas of microbiome research. It also underscores the metabolic capabilities of microbial fermentation on nutritional substrates that require further mechanistic understanding and systems biology approaches of studying functional interactions between diet composition, gut microbiota, and host metabolism. Questions surrounding bacterial fermentation and degradation of dietary constituents (particularly by Firmicutes and Bacteroidetes) and deciphering how microbial encoding of enzymes and derived metabolites affect recovery of dietary energy by the host are more complex than previously thought. Moreover, it is essential to understand to what extent the intestinal microbiota is subject to dietary control and to integrate these data with functional metabolic signatures and biomarkers. Many lines of research have demonstrated the significant role of the gut microbiota in human physiology and disease. Probiotic and prebiotic products are proliferating in the market in response to consumer demand, and the science and technology around these products are progressing rapidly. With high-throughput molecular technologies driving the science, studying the bidirectional interactions of host-microbial cometabolism, epithelial cell maturation, shaping of innate immune development, normal vs. dysfunctional nutrient absorption and processing, and the complex signaling pathways involved is now possible. Substantiating the safety and mechanisms of action of probiotic/prebiotic formulations is critical. Beneficial modulation of the human microbiota by using these nutritional and biotherapeutic strategies holds considerable promise as next

  15. [Impact of lipid metabolism parameters on the development and progression of coronary artery disease : An update].

    PubMed

    Sinning, D; Leistner, D M; Landmesser, U

    2016-06-01

    Disorders of lipid metabolism play a major role in the development and progression of coronary artery disease. Dyslipidemia therefore plays a central role in therapeutic approaches for prevention and treatment of cardiovascular events associated with coronary artery disease. Epidemiological studies have shown an association between various lipid metabolism parameters, the risk of developing coronary artery disease and progression of a pre-existing disease. In particular, increased levels of low-density lipoprotein cholesterol (LDL-C), reduced levels of HDL cholesterol (HDL-C), as well as high levels of triglycerides and increased lipoprotein(a) [Lp(a)] levels can be taken into account when assessing the risk stratification of patients for primary prevention of coronary artery disease. Lifestyle and dietary changes, intensified statin therapy and possibly the addition of ezetimibe remain the major interventions in both primary and secondary prevention of coronary artery disease, as they improve the prognosis particularly by lowering levels of LDL-C. Recently, genetic studies have contributed to extending our understanding of the relationship between lipid metabolism and coronary artery disease. A causal role for progression of coronary artery disease could be demonstrated for LDL-C, Lpa and triglyceride-rich lipoproteins (TRL), which could not be demonstrated for HDL-C in various studies. Furthermore, the effect of reduction of LDL-C by proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition and by the cholesteryl ester transfer protein (CETP) inhibitor anacetrapib on cardiovascular events is currently being investigated in large clinical outcome study programs. PMID:27215419

  16. Effect of SO/sub 2/ on light modulation of plant metabolism. Progress report

    SciTech Connect

    Anderson, L.E.

    1985-01-01

    This progress report briefly notes conclusions of work done on SO/sub 2/ effect on light modulation of plant metabolism. Conclusions include: effect of light activation on kinetic parameters of fructosebisphosphatase - for this enzyme K/sub m/ decreases and V/sub max/ increases as a result of light activation; and the effect of sulfite and arsenite on light activation in 2 Pisum cultivars - the differences in sensitivity to SO/sub 2/ is directly reflected in differences in a thylakoid bound factor (LEM) to SO/sub 2/.

  17. Cell cycle progression is an essential regulatory component of phospholipid metabolism and membrane homeostasis.

    PubMed

    Sanchez-Alvarez, Miguel; Zhang, Qifeng; Finger, Fabian; Wakelam, Michael J O; Bakal, Chris

    2015-09-01

    We show that phospholipid anabolism does not occur uniformly during the metazoan cell cycle. Transition to S-phase is required for optimal mobilization of lipid precursors, synthesis of specific phospholipid species and endoplasmic reticulum (ER) homeostasis. Average changes observed in whole-cell phospholipid composition, and total ER lipid content, upon stimulation of cell growth can be explained by the cell cycle distribution of the population. TORC1 promotes phospholipid anabolism by slowing S/G2 progression. The cell cycle stage-specific nature of lipid biogenesis is dependent on p53. We propose that coupling lipid metabolism to cell cycle progression is a means by which cells have evolved to coordinate proliferation with cell and organelle growth. PMID:26333836

  18. Metabolic Tumor Burden Predicts for Disease Progression and Death in Lung Cancer

    SciTech Connect

    Lee, Percy; Weerasuriya, Dilani K.; Lavori, Philip W.; Quon, Andrew; Hara, Wendy; Maxim, Peter G.; Le, Quynh-Thu; Wakelee, Heather A.; Donington, Jessica S.; Graves, Edward E.; Loo, Billy W.

    2007-10-01

    Purpose: In lung cancer, stage is an important prognostic factor for disease progression and survival. However, stage may be simply a surrogate for underlying tumor burden. Our purpose was to assess the prognostic value of tumor burden measured by {sup 18}F-fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging. Patients and Methods: We identified 19 patients with lung cancer who had staging PET-CT scans before any therapy, and adequate follow-up (complete to time of progression for 18, and death for 15 of 19). Metabolically active tumor regions were segmented on pretreatment PET scans semi-automatically using custom software. We determined the relationship between times to progression (TTP) and death (OS) and two PET parameters: total metabolic tumor volume (MTV), and standardized uptake value (SUV). Results: The estimated median TTP and OS for the cohort were 9.3 months and 14.8 months. On multivariate Cox proportional hazards regression analysis, an increase in MTV of 25 ml (difference between the 75th and 25th percentiles) was associated with increased hazard of progression and of death (5.4-fold and 7.6-fold), statistically significant (p = 0.0014 and p = 0.001) after controlling for stage, treatment intent (definitive or palliative), age, Karnofsky performance status, and weight loss. We did not find a significant relationship between SUV and TTP or OS. Conclusions: In this study, high tumor burden assessed by PET MTV is an independent poor prognostic feature in lung cancer, promising for stratifying patients in randomized trials and ultimately for selecting risk-adapted therapies. These results will need to be validated in larger cohorts with longer follow-up, and evaluated prospectively.

  19. 77 FR 26316 - Progress Energy Florida; Final Environmental Impact Statement for Combined Licenses for Levy...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-03

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Progress Energy Florida; Final Environmental Impact Statement for Combined Licenses for Levy Nuclear Plant Units 1 and 2 Notice is hereby given that the U.S. Nuclear Regulatory Commission (NRC or the Commission) and the U.S. Army Corps of...

  20. Current progress of targetron technology: development, improvement and application in metabolic engineering.

    PubMed

    Liu, Ya-Jun; Zhang, Jie; Cui, Gu-Zhen; Cui, Qiu

    2015-06-01

    Targetrons are mobile group II introns that can recognize their DNA target sites by base-pairing RNA-DNA interactions with the aid of site-specific binding reverse transcriptases. Targetron technology stands out from recently developed gene targeting methods because of the flexibility, feasibility, and efficiency, and is particularly suitable for the genetic engineering of difficult microorganisms, including cellulolytic bacteria that are considered promising candidates for biomass conversion via consolidated bioprocessing. Along with the development of the thermotargetron method for thermophiles, targetron technology becomes increasingly important for the metabolic engineering of industrial microorganisms aiming at biofuel/chemical production. To summarize the current progress of targetron technology and provide new insights on the use of the technology, this paper reviews the retrohoming mechanisms of both mesophilic and thermophilic targetron methods based on various group II introns, investigates the improvement of targetron tools for high target efficiency and specificity, and discusses the current applications in the metabolic engineering for bacterial producers. Although there are still intellectual property and technical restrictions in targetron applications, we propose that targetron technology will contribute to both biochemistry research and the metabolic engineering for industrial productions. PMID:25735546

  1. Recent progress in development of synthetic biology platforms and metabolic engineering of Corynebacterium glutamicum.

    PubMed

    Woo, Han Min; Park, Jin-Byung

    2014-06-20

    The paradigm of synthetic biology has been evolving, along with relevant engineering, to achieve designed bio-systems. Synthetic biology has reached the point where it is possible to develop microbial strains to produce desired chemicals. Recent advances in this field have promoted metabolic engineering of Corynebacterium glutamicum as an amino-acid producer for use in intelligent microbial-cell factories. Here, we review recent advances that address C. glutamicum as a potential model organism for synthetic biology, and evaluate their industrial applications. Finally, we highlight the perspective of developing C. glutamicum as a step toward advanced microbial-cell factories that could produce valuable chemicals from renewable resources. PMID:24632177

  2. Obesity dependent metabolic signatures associated with nonalcoholic fatty liver disease progression

    PubMed Central

    Barr, J.; Caballería, J.; Martínez-Arranz, I.; Domínguez-Díez, A.; Alonso, C.; Muntané, J.; Pérez-Cormenzana, M.; García-Monzón, C.; Mayo, R.; Martín-Duce, A.; Romero-Gómez, M.; Iacono, O. Lo; Tordjman, J.; Andrade, R.J.; Pérez-Carreras, M.; Le Marchand-Brustel, Y.; Tran, A.; Fernández-Escalante, C.; Arévalo, E.; García–Unzueta, M.; Clement, K.; Crespo, J.; Gual, P.; Gómez-Fleitas, M.; Martínez-Chantar, M.L.; Castro, A.; Lu, S.C.; Vázquez-Chantada, M.; Mato, J.M.

    2012-01-01

    Our understanding of the mechanisms by which nonalcoholic fatty liver disease (NAFLD) progresses from simple steatosis to steatohepatitis (NASH) is still very limited. Despite the growing number of studies linking the disease with altered serum metabolite levels, an obstacle to the development of metabolome-based NAFLD predictors has been the lack of large cohort data from biopsy-proven patients matched for key metabolic features such as obesity. We studied 467 biopsied individuals with normal liver histology (n=90) or diagnosed with NAFLD (steatosis, n=246; NASH, n=131), randomly divided into estimation (80% of all patients) and validation (20% of all patients) groups. Qualitative determinations of 540 serum metabolite variables were performed using ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS). The metabolic profile was dependent on patient body-mass index (BMI), suggesting that the NAFLD pathogenesis mechanism may be quite different depending on an individual’s level of obesity. A BMI-stratified multivariate model based on the NAFLD serum metabolic profile was used to separate patients with and without NASH. The area under the receiver operating characteristic curve was 0.87 in the estimation and 0.85 in the validation group. The cutoff (0.54) corresponding to maximum average diagnostic accuracy (0.82) predicted NASH with a sensitivity of 0.71 and a specificity of 0.92 (negative/positive predictive values = 0.82/0.84). The present data, indicating that a BMI-dependent serum metabolic profile may be able to reliably distinguish NASH from steatosis patients, have significant implications for the development of NASH biomarkers and potential novel targets for therapeutic intervention. PMID:22364559

  3. 40 CFR 60.1630 - How do I comply with the increment of progress for achieving final compliance?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Emission Guidelines and Compliance Times for Small Municipal Waste Combustion Units Constructed on or... progress for achieving final compliance? For the final compliance increment of progress, you must complete two items: (a) Complete all process changes and complete retrofit construction as specified in...

  4. Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression.

    PubMed

    Chang, Chih-Hao; Qiu, Jing; O'Sullivan, David; Buck, Michael D; Noguchi, Takuro; Curtis, Jonathan D; Chen, Qiongyu; Gindin, Mariel; Gubin, Matthew M; van der Windt, Gerritje J W; Tonc, Elena; Schreiber, Robert D; Pearce, Edward J; Pearce, Erika L

    2015-09-10

    Failure of T cells to protect against cancer is thought to result from lack of antigen recognition, chronic activation, and/or suppression by other cells. Using a mouse sarcoma model, we show that glucose consumption by tumors metabolically restricts T cells, leading to their dampened mTOR activity, glycolytic capacity, and IFN-γ production, thereby allowing tumor progression. We show that enhancing glycolysis in an antigenic "regressor" tumor is sufficient to override the protective ability of T cells to control tumor growth. We also show that checkpoint blockade antibodies against CTLA-4, PD-1, and PD-L1, which are used clinically, restore glucose in tumor microenvironment, permitting T cell glycolysis and IFN-γ production. Furthermore, we found that blocking PD-L1 directly on tumors dampens glycolysis by inhibiting mTOR activity and decreasing expression of glycolysis enzymes, reflecting a role for PD-L1 in tumor glucose utilization. Our results establish that tumor-imposed metabolic restrictions can mediate T cell hyporesponsiveness during cancer. PMID:26321679

  5. [Physiology and genetics of metabolic flux control in Zymomonas mobilis]. Progress report

    SciTech Connect

    Conway, T.

    1992-07-01

    The funded research deals with the physiology and genetics of glycolytic flux control in Zymomonas mobilis. Two fundamental biological questions are begin addressed: First, how do the enzymes of glycolytic pathways act in concert to regulate metabolic flux? Second, what is the role of gene expression in regulating high level synthesis of the glycolytic enzymes in a balance that allows proper glycolytic flux control? The specific objectives of the grant are as follows: 1. To clone the structural and regulatory regions of the Z. mobilis genes encoding glucose-6-phosphate dehydrogenase, phosphoglucose isomerase, enolase, 6-phosphogluconate dehydratase, 2- keto-3-deoxy- 6-phosphogluconate aldolase, glucokinase and fructokinase. 2. To characterize the structure of these genes with respect to nucleotide sequence, transcriptional initiation sites promoter location, evolutionary relatedness to similar genes from other organisms, and organization of these genes on the genome. 3. To investigate the effects of genetically engineered alterations in the levels of the cloned enzymes on metabolic flux and cell growth. 4. To study transcriptional and post-transcriptional regulation of the genes encoding the enzymes of the Entner-Doudoroff pathway. The first two specific objectives have now been fully completed. Significant progress has been made on the fourth objective and work on the third objective is well underway.

  6. Global reprogramming of transcription and metabolism in Medicago truncatula during progressive drought and after rewatering

    PubMed Central

    Zhang, Ji-Yi; Cruz de Carvalho, Maria H; Torres-Jerez, Ivone; Kang, Yun; Allen, Stacy N; Huhman, David V; Tang, Yuhong; Murray, Jeremy; Sumner, Lloyd W; Udvardi, Michael K

    2014-01-01

    Medicago truncatula is a model legume forage crop native to the arid and semi-arid environments of the Mediterranean. Given its drought-adapted nature, it is an ideal candidate to study the molecular and biochemical mechanisms conferring drought resistance in plants. Medicago plants were subjected to a progressive drought stress over 14 d of water withholding followed by rewatering under controlled environmental conditions. Based on physiological measurements of plant water status and changes in morphology, plants experienced mild, moderate and severe water stress before rehydration. Transcriptome analysis of roots and shoots from control, mildly, moderately and severely stressed, and rewatered plants, identified many thousands of genes that were altered in expression in response to drought. Many genes with expression tightly coupled to the plant water potential (i.e. drought intensity) were identified suggesting an involvement in Medicago drought adaptation responses. Metabolite profiling of drought-stressed plants revealed the presence of 135 polar and 165 non-polar compounds in roots and shoots. Combining Medicago metabolomic data with transcriptomic data yielded insight into the regulation of metabolic pathways operating under drought stress. Among the metabolites detected in drought-stressed Medicago plants, myo-inositol and proline had striking regulatory profiles indicating involvement in Medicago drought tolerance. Global transcriptional and metabolic responses to drought and rewatering were investigated in Medicago truncatula, a naturally drought-adapted model legume species. Integration of metabolomic and transcriptomic data yielded insights into the regulation of metabolic pathways underlying drought-stress adaptation. Many genes and metabolites with expression tightly coupled to drought intensity were identified, suggesting active involvement in Medicago drought resistance. These could prove useful targets for future translational approaches to improve

  7. The role of proteomics in progressing insights into plant secondary metabolism

    PubMed Central

    Martínez-Esteso, María J.; Martínez-Márquez, Ascensión; Sellés-Marchart, Susana; Morante-Carriel, Jaime A.; Bru-Martínez, Roque

    2015-01-01

    The development of omics has enabled the genome-wide exploration of all kinds of biological processes at the molecular level. Almost every field of plant biology has been analyzed at the genomic, transcriptomic and proteomic level. Here we focus on the particular contribution that proteomic technologies have made in progressing knowledge and characterising plant secondary metabolism (SM) pathways since early expectations were created 15 years ago. We analyzed how three major issues in the proteomic analysis of plant SM have been implemented in various research studies. These issues are: (i) the selection of a suitable plant material rich in secondary metabolites of interest, such as specialized tissues and organs, and in vitro cell cultures; (ii) the proteomic strategy to access target proteins, either a comprehensive or a differential analysis; (iii) the proteomic approach, represented by the hypothesis-free discovery proteomics and the hypothesis-driven targeted proteomics. We also examine to what extent the most-advanced technologies have been incorporated into proteomic research in plant SM and highlight some cutting edge techniques that would strongly benefit the progress made in this field. PMID:26217358

  8. Dissolved organic matter and lake metabolism. Technical progress report, 1 July 1979-30 June 1980

    SciTech Connect

    Wetzel, R.G.

    1980-01-01

    Progress in research to evaluate the impact of utilization of fossil fuels on surface water is reported. Analyses of regulatory mechanisms of growth and rates of carbon cycling center on evaluation of quantitative control interactions among the microflora of the pelagial zones of several lakes of progressively greater eutrophy, littoral photosynthetic producer-decomposer complex, and allochthonous inorganic-organic influxes and their biotic processing. The underlying thesis is that quantification of the dynamic carbon fluxes among these components and their rate control mechanisms by physical and chemical factors are fundamental to elucidation of the rate functions of lake eutrophication. A major portion of the research has been directed towards the fate and nutrient mechanisms regulating qualitative and quantitative utilization and losses of organic carbon synthesized within lakes and their drainage basins. It has become increasingly apparent that the wetland and littoral flora, and attendant epiphytic and benthic microflora, have major regulatory controls on biogeochemical cycling of whole lake systems. A major effort on factors regulating the metabolism of littoral macrophytes and attached algae has been coupled to integrated studies on their decomposition and the fate of detrital dissolved and particulate organic matter. These organic products are being coupled to influences on enzymatic activity and inorganic nutrient cycling.

  9. Role of body composition and metabolic profile in Barrett’s oesophagus and progression to cancer

    PubMed Central

    Di Caro, Simona; Cheung, Wui Hang; Fini, Lucia; Keane, Margaret G.; Theis, Belinda; Haidry, Rehan; Di Renzo, Laura; De Lorenzo, Antonino; Lovat, Laurence; Batterham, Rachel L.

    2016-01-01

    Background and aims The aim of this study was to evaluate the risk for Barrett’s oesophagus (BE) on the basis of body composition, metabolic pathways, adipokines and metabolic syndrome (MS), as well as their role in cancer progression. Methods In patients with and without BE at gastroscopy, data on MS, BMI, waist/hip ratio for abdominal obesity (AO) and body fat percentage by bioimpedance were obtained. Fasting plasma glucose, insulin, HbA1c, lipid, serum adiponectin and leptin levels were measured. The homoeostasis model assessment (HOMA-IR) was used to estimate insulin resistance. Histological findings for BE were correlated with the above parameters. Risk factors for BE identified using univariate analysis were entered into a multivariate logistic regression analysis. Results A total of 250 patients and 224 controls (F/M: 189/285, mean age 58.08±15.51 years) were enroled. In the BE and control groups, 39.6 versus 31.3% were overweight, 32 versus 22.8% were obese, 75.6 versus 51.3% had AO, and 28.1 versus 18.9% were metabolically obese, respectively. AO [odds ratio (OR) 3.08], increased body fat percentage (OR 2.29), and higher BMI (overweight: OR 2.04; obese: OR 2.26) were significantly associated with BE. A positive trend was found in Normal Weight Obese Syndrome (OR 1.69). MS was associated with BE (overweight: OR 3.05; obese: OR 5.2; AO: OR 8.08). Insulin levels (P=0.05) and HOMA-IR (P<0.001) were higher in BE. AO was the only independent risk factor associated with BE (OR 1.65; P=0.02) and high-grade dysplasia (OR 2.44) on multivariate analysis. Conclusion AO was strongly associated with BE and dysplasia. BE was associated with MS and higher insulin/HOMA-IR, suggesting the activation of specific metabolic pathways in patients with altered body composition. PMID:26671515

  10. Correlating Structure and Function of Drug-Metabolizing Enzymes: Progress and Ongoing Challenges

    PubMed Central

    Johnson, Eric F.; Connick, J. Patrick; Reed, James R.; Backes, Wayne L.; Desai, Manoj C.; Xu, Lianhong; Estrada, D. Fernando; Laurence, Jennifer S.

    2014-01-01

    This report summarizes a symposium sponsored by the American Society for Pharmacology and Experimental Therapeutics at Experimental Biology held April 20-24 in Boston, MA. Presentations discussed the status of cytochrome P450 (P450) knowledge, emphasizing advances and challenges in relating structure with function and in applying this information to drug design. First, at least one structure of most major human drug-metabolizing P450 enzymes is known. However, the flexibility of these active sites can limit the predictive value of one structure for other ligands. A second limitation is our coarse-grain understanding of P450 interactions with membranes, other P450 enzymes, NADPH–cytochrome P450 reductase, and cytochrome b5. Recent work has examined differential P450 interactions with reductase in mixed P450 systems and P450:P450 complexes in reconstituted systems and cells, suggesting another level of functional control. In addition, protein nuclear magnetic resonance is a new approach to probe these protein/protein interactions, identifying interacting b5 and P450 surfaces, showing that b5 and reductase binding are mutually exclusive, and demonstrating ligand modulation of CYP17A1/b5 interactions. One desired outcome is the application of such information to control drug metabolism and/or design selective P450 inhibitors. A final presentation highlighted development of a CYP3A4 inhibitor that slows clearance of human immunodeficiency virus drugs otherwise rapidly metabolized by CYP3A4. Although understanding P450 structure/function relationships is an ongoing challenge, translational advances will benefit from continued integration of existing and new biophysical approaches. PMID:24130370

  11. Testosterone deficiency induced by progressive stages of diabetes mellitus impairs glucose metabolism and favors glycogenesis in mature rat Sertoli cells.

    PubMed

    Rato, Luís; Alves, Marco G; Duarte, Ana I; Santos, Maria S; Moreira, Paula I; Cavaco, José E; Oliveira, Pedro F

    2015-09-01

    The incidence of type 2 diabetes mellitus and its prodromal stage, pre-diabetes, is rapidly increasing among young men, leading to disturbances in testosterone synthesis. However, the impact of testosterone deficiency induced by these progressive stages of diabetes on the metabolic behavior of Sertoli cells remains unknown. We evaluated the effects of testosterone deficiency associated with pre-diabetes and type 2 diabetes on Sertoli cells metabolism, by measuring (1) the expression and/or activities of glycolysis and glycogen metabolism-related proteins and (2) the metabolite secretion/consumption in Sertoli cells obtained from rat models of different development stages of the disease, to unveil the mechanisms by which testosterone deregulation may affect spermatogenesis. Glucose and pyruvate uptake were decreased in cells exposed to the testosterone concentration found in pre-diabetic rats (600nM), whereas the decreased testosterone concentrations found in type 2 diabetic rats (7nM) reversed this profile. Lactate production was not altered, although the expression and/or activity of lactate dehydrogenase and monocarboxylate transporter 4 were affected by progressive testosterone-deficiency. Sertoli cells exposed to type 2 diabetic conditions exhibited intracellular glycogen accumulation. These results illustrate that gradually reduced levels of testosterone, induced by progressive stages of diabetes mellitus, favor a metabolic reprogramming toward glycogen synthesis. Our data highlights a pivotal role for testosterone in the regulation of spermatogenesis metabolic support by Sertoli cells, particularly in individuals suffering from metabolic diseases. Such alterations may be in the basis of male subfertility/infertility associated with the progression of diabetes mellitus. PMID:26148570

  12. Cyclin D1-Cdk4 controls glucose metabolism independently of cell cycle progression.

    PubMed

    Lee, Yoonjin; Dominy, John E; Choi, Yoon Jong; Jurczak, Michael; Tolliday, Nicola; Camporez, Joao Paulo; Chim, Helen; Lim, Ji-Hong; Ruan, Hai-Bin; Yang, Xiaoyong; Vazquez, Francisca; Sicinski, Piotr; Shulman, Gerald I; Puigserver, Pere

    2014-06-26

    Insulin constitutes a principal evolutionarily conserved hormonal axis for maintaining glucose homeostasis; dysregulation of this axis causes diabetes. PGC-1α (peroxisome-proliferator-activated receptor-γ coactivator-1α) links insulin signalling to the expression of glucose and lipid metabolic genes. The histone acetyltransferase GCN5 (general control non-repressed protein 5) acetylates PGC-1α and suppresses its transcriptional activity, whereas sirtuin 1 deacetylates and activates PGC-1α. Although insulin is a mitogenic signal in proliferative cells, whether components of the cell cycle machinery contribute to its metabolic action is poorly understood. Here we report that in mice insulin activates cyclin D1-cyclin-dependent kinase 4 (Cdk4), which, in turn, increases GCN5 acetyltransferase activity and suppresses hepatic glucose production independently of cell cycle progression. Through a cell-based high-throughput chemical screen, we identify a Cdk4 inhibitor that potently decreases PGC-1α acetylation. Insulin/GSK-3β (glycogen synthase kinase 3-beta) signalling induces cyclin D1 protein stability by sequestering cyclin D1 in the nucleus. In parallel, dietary amino acids increase hepatic cyclin D1 messenger RNA transcripts. Activated cyclin D1-Cdk4 kinase phosphorylates and activates GCN5, which then acetylates and inhibits PGC-1α activity on gluconeogenic genes. Loss of hepatic cyclin D1 results in increased gluconeogenesis and hyperglycaemia. In diabetic models, cyclin D1-Cdk4 is chronically elevated and refractory to fasting/feeding transitions; nevertheless further activation of this kinase normalizes glycaemia. Our findings show that insulin uses components of the cell cycle machinery in post-mitotic cells to control glucose homeostasis independently of cell division. PMID:24870244

  13. Cyclin D1-CDK4 Controls Glucose Metabolism Independently of Cell Cycle Progression

    PubMed Central

    Lee, Yoonjin; Dominy, John E.; Choi, Yoon Jong; Jurczak, Michael; Tolliday, Nicola; Camporez, Joao Paulo; Chim, Helen; Lim, Ji-Hong; Ruan, Hai-Bin; Yang, Xiaoyong; Vazquez, Francisca; Sicinski, Piotr; Shulman, Gerald I.; Puigserver, Pere

    2014-01-01

    Insulin constitutes a major evolutionarily conserved hormonal axis for maintaining glucose homeostasis1-3; dysregulation of this axis causes diabetes2,4. PGC-1α links insulin signaling to the expression of glucose and lipid metabolic genes5-7. GCN5 acetylates PGC-1α and suppresses its transcriptional activity, whereas SIRT1 deacetylates and activates PGC-1α8,9. Although insulin is a mitogenic signal in proliferative cells10,11, whether components of the cell cycle machinery contribute to insulin’s metabolic action is poorly understood. Herein, we report that insulin activates cyclin D1-CDK4, which, in turn, increases GCN5 acetyltransferase activity and suppresses hepatic glucose production independently of cell cycle progression. Through a cell-based high throughput chemical screen, we identified a CDK4 inhibitor that potently decreases PGC-1α acetylation. Insulin/GSK3β signaling induces cyclin D1 protein stability via sequestering cyclin D1 in the nucleus. In parallel, dietary amino acids increase hepatic cyclin D1 mRNA transcripts. Activated cyclin D1-CDK4 kinase phosphorylates and activates GCN5, which then acetylates and inhibits PGC-1α activity on gluconeogenic genes. Loss of hepatic cyclin D1 results in increased gluconeogenesis and hyperglycemia. In diabetic models, cyclin D1-CDK4 is chronically elevated and refractory to fasting/feeding transitions; nevertheless further activation of this kinase normalizes glycemia. Our findings show that insulin uses components of the cell cycle machinery in post-mitotic cells to control glucose homeostasis independently of cell division. PMID:24870244

  14. Regulation of terpene metabolism. Final technical report, March 15, 1988--March 14, 1996

    SciTech Connect

    Croteau, R.

    1996-12-31

    This research focuses on the following topics: the biosynthesis and catabolism of monoterpenes; the organization of monoterpene metabolism; the developmental regulation of monoterpene metabolism; the flux control of precursor supply; and the integration of monoterpene and higher terpenoid metabolism.

  15. Final Progress Report - Grant No.DE-FG02-98ER62558

    SciTech Connect

    Smith, T.F.

    2003-05-01

    This final progress report contains a comparison of actual accomplishments with the goals and objectives proposed for the period. It was proposed in the original aims of the proposal that an integrated set of gene sequence/function/structure analysis tools be assembled to support maximal extraction functional information from among the available complete genome Open Reading Frames (ORFs) and their probable regulatory regions. This report lists the progress that was made on these three major components of the proposal: (1) The construction of diagnostic functional patterns/profiles for all probable protein functional domains. (2) The development of methodologies needed to construct full hash tables and associated ORF distributions of all possible regulatory words. The development of sequence comparative tools to search for and identify regulatory circuits among sets of coordinately regulated genes. (3) The construction of prototype data structures, assembled (and updated) from existing databases and other data resources, to support the above developments and their validation.

  16. Flow-induced vibration for light water reactors. Final progress report, July 1981-September 1981

    SciTech Connect

    Torres, M.R.

    1981-11-01

    Flow-Induced Vibration for Light Water Reactors (FIV for LWRs) is a program designed to improve the FIV performance of light water reactors through the development of design criteria, analytical models for predicting behavior of components, and general scaling laws to improve the accuracy of reduced-scale tests, and through the identification of high FIV risk areas. The program is managed by the General Electric Nuclear Power Systems Engineering Department and has three major contributors: General Electric Nuclear Power Systems Engineering Department (NPSED), General Electric Corporate Research and Development (CR and D) and Argonne National Laboratory (ANL). The program commenced December 1, 1976. This progress report summarizes the accomplishments achieved during the final period from July 1981 to September 1981. This is the last quarterly progress report to be issued for this program.

  17. Nonlinear and Nonideal MHD. Final annual progress report, January 1, 2003 through December 31, 2003

    SciTech Connect

    Callen, James D

    2003-04-30

    This is the third and final annual progress report on the current 3-year ''Nonlinear and Nonideal MHD'' DoE grand DE-FG02-86ER53218 for the six months since the November 2002 progress report. During this grant year the funding level was $309k. The participating personnel and their approximate degree of funded involvement in this research project this grant year has been as follows: Professor J. D. Callen (PI, 1.8 months during academic year, 2.2 summer months); Professor C.C. Hegna (Co-PI: 2.3 months during academic year, 1.5 summer months); postdoc Dr. S. Gupta (100%); and graduate students A.L. Garcia-Perciante (50% RA) and X. Liu (50% RA).

  18. Extreme Performance Scalable Operating Systems Final Progress Report (July 1, 2008 - October 31, 2011)

    SciTech Connect

    Malony, Allen D; Shende, Sameer

    2011-10-31

    This is the final progress report for the FastOS (Phase 2) (FastOS-2) project with Argonne National Laboratory and the University of Oregon (UO). The project started at UO on July 1, 2008 and ran until April 30, 2010, at which time a six-month no-cost extension began. The FastOS-2 work at UO delivered excellent results in all research work areas: * scalable parallel monitoring * kernel-level performance measurement * parallel I/0 system measurement * large-scale and hybrid application performance measurement * onlne scalable performance data reduction and analysis * binary instrumentation

  19. Genetic alterations in fatty acid transport and metabolism genes are associated with metastatic progression and poor prognosis of human cancers

    PubMed Central

    Nath, Aritro; Chan, Christina

    2016-01-01

    Reprogramming of cellular metabolism is a hallmark feature of cancer cells. While a distinct set of processes drive metastasis when compared to tumorigenesis, it is yet unclear if genetic alterations in metabolic pathways are associated with metastatic progression of human cancers. Here, we analyzed the mutation, copy number variation and gene expression patterns of a literature-derived model of metabolic genes associated with glycolysis (Warburg effect), fatty acid metabolism (lipogenesis, oxidation, lipolysis, esterification) and fatty acid uptake in >9000 primary or metastatic tumor samples from the multi-cancer TCGA datasets. Our association analysis revealed a uniform pattern of Warburg effect mutations influencing prognosis across all tumor types, while copy number alterations in the electron transport chain gene SCO2, fatty acid uptake (CAV1, CD36) and lipogenesis (PPARA, PPARD, MLXIPL) genes were enriched in metastatic tumors. Using gene expression profiles, we established a gene-signature (CAV1, CD36, MLXIPL, CPT1C, CYP2E1) that strongly associated with epithelial-mesenchymal program across multiple cancers. Moreover, stratification of samples based on the copy number or expression profiles of the genes identified in our analysis revealed a significant effect on patient survival rates, thus confirming prominent roles of fatty acid uptake and metabolism in metastatic progression and poor prognosis of human cancers. PMID:26725848

  20. Genetic alterations in fatty acid transport and metabolism genes are associated with metastatic progression and poor prognosis of human cancers.

    PubMed

    Nath, Aritro; Chan, Christina

    2016-01-01

    Reprogramming of cellular metabolism is a hallmark feature of cancer cells. While a distinct set of processes drive metastasis when compared to tumorigenesis, it is yet unclear if genetic alterations in metabolic pathways are associated with metastatic progression of human cancers. Here, we analyzed the mutation, copy number variation and gene expression patterns of a literature-derived model of metabolic genes associated with glycolysis (Warburg effect), fatty acid metabolism (lipogenesis, oxidation, lipolysis, esterification) and fatty acid uptake in >9000 primary or metastatic tumor samples from the multi-cancer TCGA datasets. Our association analysis revealed a uniform pattern of Warburg effect mutations influencing prognosis across all tumor types, while copy number alterations in the electron transport chain gene SCO2, fatty acid uptake (CAV1, CD36) and lipogenesis (PPARA, PPARD, MLXIPL) genes were enriched in metastatic tumors. Using gene expression profiles, we established a gene-signature (CAV1, CD36, MLXIPL, CPT1C, CYP2E1) that strongly associated with epithelial-mesenchymal program across multiple cancers. Moreover, stratification of samples based on the copy number or expression profiles of the genes identified in our analysis revealed a significant effect on patient survival rates, thus confirming prominent roles of fatty acid uptake and metabolism in metastatic progression and poor prognosis of human cancers. PMID:26725848

  1. 40 CFR 62.15040 - What are the requirements for meeting increments of progress and achieving final compliance?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Combustion Units Constructed on or Before August 30, 1999 Compliance Schedule and Increments of Progress § 62.... (3) Initiate onsite construction. (4) Complete onsite construction. (5) Achieve final compliance....

  2. A glycolytic phenotype is associated with prostate cancer progression and aggressiveness: a role for monocarboxylate transporters as metabolic targets for therapy

    PubMed Central

    Pertega-Gomes, Nelma; Felisbino, Sergio; Massie, Charlie E; Vizcaino, Jose R; Coelho, Ricardo; Sandi, Chiranjeevi; Simoes-Sousa, Susana; Jurmeister, Sarah; Ramos-Montoya, Antonio; Asim, Mohammad; Tran, Maxine; Oliveira, Elsa; Lobo da Cunha, Alexandre; Maximo, Valdemar; Baltazar, Fatima; Neal, David E; Fryer, Lee GD

    2015-01-01

    Metabolic adaptation is considered an emerging hallmark of cancer, whereby cancer cells exhibit high rates of glucose consumption with consequent lactate production. To ensure rapid efflux of lactate, most cancer cells express high levels of monocarboxylate transporters (MCTs), which therefore may constitute suitable therapeutic targets. The impact of MCT inhibition, along with the clinical impact of altered cellular metabolism during prostate cancer (PCa) initiation and progression, has not been described. Using a large cohort of human prostate tissues of different grades, in silico data, in vitro and ex vivo studies, we demonstrate the metabolic heterogeneity of PCa and its clinical relevance. We show an increased glycolytic phenotype in advanced stages of PCa and its correlation with poor prognosis. Finally, we present evidence supporting MCTs as suitable targets in PCa, affecting not only cancer cell proliferation and survival but also the expression of a number of hypoxia-inducible factor target genes associated with poor prognosis. Herein, we suggest that patients with highly glycolytic tumours have poorer outcome, supporting the notion of targeting glycolytic tumour cells in prostate cancer through the use of MCT inhibitors. © 2015 Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID:25875424

  3. Metabolism

    MedlinePlus

    Metabolism refers to all the physical and chemical processes in the body that convert or use energy, ... Tortora GJ, Derrickson BH. Metabolism. In: Tortora GJ, Derrickson BH. Principles of Anatomy and Physiology . 14th ed. Hoboken, NJ: John H Wiley and Sons; 2013: ...

  4. Recent progress in vitamin D metabolism and the chemistry of vitamin D metabolites

    SciTech Connect

    Schnoes, H.K.; DeLuca, H.F.

    1980-08-01

    The molecular mechanism of action of vitamin D and the elucidation of the vitamin D endocrine system are illustrated by selected examples of recent chemical work in our laboratories. One of these is the isolation and identification of vitamin D/sub 3/ as the antirachitic substance produced in irradiated skin. A second is the isolation and identification of the calcitroic acid, a major metabolite of 1,25-dihydroxyvitamin D/sub 3/ with potential function. A third is the isolation and identification of 25-hydroxyvitamin D/sub 3/-26,23-lactone, a major metabolite of vitamin D in the plasma of animals given large amounts of vitamin D. A fourth is a detailed study of 24,24-difluoro-25-hydroxyvitamin D/sub 3/ to test whether 24-hydroxylation plays an important role in the function of vitamin D. Other important developments include the chemical synthesis of high specific activity radioactive vitamin D metabolites for use in the elucidation of their molecular mechanism of action, cellular sites of action, and in quantitative metabolite assays. Finally, recent progress in synthetic methodology, providing a convenient route to 1..cap alpha..-hydroxylated vitamin D compounds, is summarized.

  5. Expression profiling in progressive stages of fumarate-hydratase deficiency: the contribution of metabolic changes to tumorigenesis.

    PubMed

    Ashrafian, Houman; O'Flaherty, Linda; Adam, Julie; Steeples, Violetta; Chung, Yuen-Li; East, Phil; Vanharanta, Sakari; Lehtonen, Heli; Nye, Emma; Hatipoglu, Emine; Miranda, Melroy; Howarth, Kimberley; Shukla, Deepa; Troy, Helen; Griffiths, John; Spencer-Dene, Bradley; Yusuf, Mohammed; Volpi, Emanuela; Maxwell, Patrick H; Stamp, Gordon; Poulsom, Richard; Pugh, Christopher W; Costa, Barbara; Bardella, Chiara; Di Renzo, Maria Flavia; Kotlikoff, Michael I; Launonen, Virpi; Aaltonen, Lauri; El-Bahrawy, Mona; Tomlinson, Ian; Pollard, Patrick J

    2010-11-15

    Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by mutations in the Krebs cycle enzyme fumarate hydratase (FH). It has been proposed that "pseudohypoxic" stabilization of hypoxia-inducible factor-α (HIF-α) by fumarate accumulation contributes to tumorigenesis in HLRCC. We hypothesized that an additional direct consequence of FH deficiency is the establishment of a biosynthetic milieu. To investigate this hypothesis, we isolated primary mouse embryonic fibroblast (MEF) lines from Fh1-deficient mice. As predicted, these MEFs upregulated Hif-1α and HIF target genes directly as a result of FH deficiency. In addition, detailed metabolic assessment of these MEFs confirmed their dependence on glycolysis, and an elevated rate of lactate efflux, associated with the upregulation of glycolytic enzymes known to be associated with tumorigenesis. Correspondingly, Fh1-deficient benign murine renal cysts and an advanced human HLRCC-related renal cell carcinoma manifested a prominent and progressive increase in the expression of HIF-α target genes and in genes known to be relevant to tumorigenesis and metastasis. In accord with our hypothesis, in a variety of different FH-deficient tissues, including a novel murine model of Fh1-deficient smooth muscle, we show a striking and progressive upregulation of a tumorigenic metabolic profile, as manifested by increased PKM2 and LDHA protein. Based on the models assessed herein, we infer that that FH deficiency compels cells to adopt an early, reversible, and progressive protumorigenic metabolic milieu that is reminiscent of that driving the Warburg effect. Targets identified in these novel and diverse FH-deficient models represent excellent potential candidates for further mechanistic investigation and therapeutic metabolic manipulation in tumors. PMID:20978192

  6. Applications of mass spectrometry in drug metabolism: 50 years of progress.

    PubMed

    Wen, Bo; Zhu, Mingshe

    2015-02-01

    Mass spectrometry plays a pivotal role in drug metabolism studies, which are an integral part of drug discovery and development nowadays. Metabolite identification has become critical to understanding the metabolic fate of drug candidates and to aid lead optimization with improved metabolic stability, toxicology and efficacy profiles. Ever since the introduction of atmospheric ionization techniques in the early 1990s, liquid chromatography coupled with mass spectrometry (LC/MS) has secured a central role as the predominant analytical platform for metabolite identification as LC and MS technologies continually advanced. In this review, we discuss the evolution of both MS technology and its applications over the past 50 years to meet the increasing demand of drug metabolism studies. These advances include ionization sources, mass analyzers, a wide range of MS acquisition strategies and data mining tools that have substantially accelerated the metabolite identification process and changed the overall drug metabolism landscape. Exemplary applications for characterization and identification of both small-molecule xenobiotics and biological macromolecules are described. In addition, this review discusses novel MS technologies and applications, including xenobiotic metabolomics that hold additional promise for advancing drug metabolism research, and offers thoughts on remaining challenges in studying the metabolism and disposition of drugs and other xenobiotics. PMID:25639893

  7. Implications of quantum metabolism and natural selection for the origin of cancer cells and tumor progression

    NASA Astrophysics Data System (ADS)

    Davies, Paul; Demetrius, Lloyd A.; Tuszynski, Jack A.

    2012-03-01

    Empirical studies give increased support for the hypothesis that the sporadic form of cancer is an age-related metabolic disease characterized by: (a) metabolic dysregulation with random abnormalities in mitochondrial DNA, and (b) metabolic alteration - the compensatory upregulation of glycolysis to offset mitochondrial impairments. This paper appeals to the theory of Quantum Metabolism and the principles of natural selection to formulate a conceptual framework for a quantitative analysis of the origin and proliferation of the disease. Quantum Metabolism, an analytical theory of energy transduction in cells inspired by the methodology of the quantum theory of solids, elucidates the molecular basis for differences in metabolic rate between normal cells, utilizing predominantly oxidative phosphorylation, and cancer cells utilizing predominantly glycolysis. The principles of natural selection account for the outcome of competition between the two classes of cells. Quantum Metabolism and the principles of natural selection give an ontogenic and evolutionary rationale for cancer proliferation and furnish a framework for effective therapeutic strategies to impede the spread of the disease.

  8. Carbon metabolism in legume nodules. Progress report, July 1982-July 1983

    SciTech Connect

    LaRue, T.A.

    1983-01-01

    The goal is to understand how the legume nodule metabolizes carbohydrate to provide energy and reductant for symbiotic fixation. The working hypothesis has been that the plant cytosol is microacrobic and that some carbon metabolism may be via anaerobic pathways similar to those in roots of flood tolerant plants. A method of analyzing redox changes in intact mitochondria, bacteroids or bacteria was adapted; a method of manipulating nitrogenase activity by oxygen inhibition was developed; the production of alcohol by soybean nodules was studied; and enzymes metabolizing alcohol/aldehyde were found in other nitrogen fixing systems. (ACR)

  9. [Research progress of the gene polymorphisms of metabolic enzyme related to polycyclic aromatic hydrocarbons risk of preterm birth].

    PubMed

    Liu, N; Li, Z W

    2016-05-01

    The etiology and underlying biological mechanisms for preterm birth are relatively intricate, involving both genetic and environmental factors. Therefore, in the process of research on environmental factors of preterm birth, individual genetic susceptibility is an important aspect which cannot be ignored. Detoxification and metabolism abilities of enzymes to the environmental toxins is determined by their genetic polymorphism, which directly affect the toxic effects of poison. The measurement of gene polymorphisms related to metabolic enzymes may have important significance in the research of biological mechanisms, the risk prediction for preterm birth and the development of the preventive measures. In the recent studies, exposure to polycyclic aromatic hydrocarbons (PAH) seems to be an important risk factor for preterm birth. Cytochrome P450 (CYP450s) and glutathione S-transferases (GSTs) are the main metabolic enzymes of PAH and many other xenobiotics, and the polymorphisms of CYP1A1, CYP2E1, GSTM1, GSTT1 and GSTT2 may be associated with the risk of preterm birth. In this paper, we summarized that the research progress on the relationship between the gene polymorphisms of metabolic enzyme related to PAH and the risk of preterm birth. PMID:27141907

  10. Carbon monoxide metabolism by the photosynthetic bacterium Rhodospirillum rubrum. Progress report, November 15, 1990--November 15, 1991

    SciTech Connect

    Ludden, P.W.; Roberts, G.P.

    1991-12-31

    Research continued on carbon monoxide metabolism by Rhodospirillum rubrum. In the past year, progress was made in: (1) the identification and isolation of the physiological electron carrier from monoxide dehydrogenase (CODH) to hydrogenase in R. rubrum; (2) the isolation, sequencing and mutagenesis of the genes encoding the components of the CO oxidation system in R. rubrum, (3) the purification and characterization of the CO-induced hydrogenase activity of R. rubrum; (4) the spectroscopic investigation of the cobalt-substituted form of the enzyme.

  11. Quantitative Tools for Dissection of Hydrogen-Producing Metabolic Networks-Final Report

    SciTech Connect

    Rabinowitz, Joshua D.; Dismukes, G.Charles.; Rabitz, Herschel A.; Amador-Noguez, Daniel

    2012-10-19

    During this project we have pioneered the development of integrated experimental-computational technologies for the quantitative dissection of metabolism in hydrogen and biofuel producing microorganisms (i.e. C. acetobutylicum and various cyanobacteria species). The application of these new methodologies resulted in many significant advances in the understanding of the metabolic networks and metabolism of these organisms, and has provided new strategies to enhance their hydrogen or biofuel producing capabilities. As an example, using mass spectrometry, isotope tracers, and quantitative flux-modeling we mapped the metabolic network structure in C. acetobutylicum. This resulted in a comprehensive and quantitative understanding of central carbon metabolism that could not have been obtained using genomic data alone. We discovered that biofuel production in this bacterium, which only occurs during stationary phase, requires a global remodeling of central metabolism (involving large changes in metabolite concentrations and fluxes) that has the effect of redirecting resources (carbon and reducing power) from biomass production into solvent production. This new holistic, quantitative understanding of metabolism is now being used as the basis for metabolic engineering strategies to improve solvent production in this bacterium. In another example, making use of newly developed technologies for monitoring hydrogen and NAD(P)H levels in vivo, we dissected the metabolic pathways for photobiological hydrogen production by cyanobacteria Cyanothece sp. This investigation led to the identification of multiple targets for improving hydrogen production. Importantly, the quantitative tools and approaches that we have developed are broadly applicable and we are now using them to investigate other important biofuel producers, such as cellulolytic bacteria.

  12. Rawlins UCG Demonstration Project. Final technical progress report, January 1, 1987--February 9, 1988

    SciTech Connect

    Not Available

    1988-08-03

    Department of Energy Participation in the Rawlins UCG Demonstration Project began officially on November 9, 1987. Even though their financial participation began at this time, they will receive technical information from the start of the project which was on January 1, 1987. The Rawlins UCG Demonstration Project is progressing in Phase I with the majority of the emphasis on facility design, site characterization and the environmental work. The site characterization field work is estimated to be completed by the end of February with the final report completion towards the end of Phase I. The facility design effort is close to the 40% level. It is anticipated that all permits will be applied for in Phase I and most of them will be granted by the end of Phase I. The obtaining of the private financing continues to be a major activity in the project. All of the financing must be in place before the continuation for DOE funding to Phase II will be applied for.

  13. 40 CFR 62.15085 - How do I comply with the increment of progress for achieving final compliance?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... municipal waste combustion unit identified in the final control plan and complete process changes to the... DESIGNATED FACILITIES AND POLLUTANTS Federal Plan Requirements for Small Municipal Waste Combustion Units... of progress, you must complete two items: (a) Complete all process changes and complete...

  14. Final Technical Progress Report: Development of Low-Cost Suspension Heliostat; December 7, 2011 - December 6, 2012

    SciTech Connect

    Bender, W.

    2013-01-01

    Final technical progress report of SunShot Incubator Solaflect Energy. The project succeeded in demonstrating that the Solaflect Suspension Heliostat design is viable for large-scale CSP installations. Canting accuracy is acceptable and is continually improving as Solaflect improves its understanding of this design. Cost reduction initiatives were successful, and there are still many opportunities for further development and further cost reduction.

  15. Newborn Screening for Genetic-Metabolic Diseases: Progress, Principles and Recommendations.

    ERIC Educational Resources Information Center

    Holtzman, Neil A.

    This monograph, designed for persons involved in the organization and regulation of screening of newborns infants for Phenylketonuria (PKU) and other genetic-metabolic diseases reviews new developments in the field, makes recommendations, and provides information about specific conditions other than PKU that are detectable by screening. Discussed…

  16. Twenty-five years of progress in bilirubin metabolism (1952-77).

    PubMed Central

    Billing, B H

    1978-01-01

    This review deals with the development of our understanding of the chemistry of bilirubin and its glucuronide derivatives during the years 1952-1977. It examines the relation between haem metabolism and bilirubin formation and our present knowledge of hepatic transport of bilirubin. The heterogeneity of familial hyperbilirubinaemia is discussed. PMID:98394

  17. Physiology and genetics of metabolic flux control in Zymomonas mobilis. Progress report

    SciTech Connect

    Conway, T.

    1992-08-01

    This work seeks to understand the role of gene expression in regulating glycolytic enzyme synthesis in a balance that allows proper glycoltic flux control. The seven genes targeted for study in this laboratory have been cloned and sequenced, and molecular details of regulation have been investigated. Clear that glycolytic enzyme synthesis is coordinated to prevent the build up of toxic metabolic intermediates. The genetic mechanisms responsible for regulating balanced expression of the EntnerDoudoroff and glycolytic genes in Z. mobilis are beginning to be understood. Several layers of genetic control, perhaps in a hierarchal arrangement act in concert to determine the relative abundance of the glycolytic enzymes. These genetic controls involve differential translational efficiency, highly conserved promoter sequences, transcription factors, differential mRNA stabilities, and nucleolytic mRNA processing. The serendipitous cloning of the glucose facilitator, glf, as a result of linkage to several other genes of interest will have a significant impact on the study of Z. mobilis metabolism. The glucose facilitator is being characterized in a genetically reconstituted system in E. coli. Molecular genetic studies indicate that the ratio of glf expression to that of glk, zmf, and edd is carefully regulated, and suggests a critical role in metabolic control. Regulation of glycolytic gene expression is now sufficiently well understood to allow use of the glycolytic genes as tools to manipulate specified enzyme levels for the purpose of analyzing metabolic flux control. The critical genes have been subcloned for stable expression in Z. mobilis and placed under control of a regulated promoter system involving the tac promoter, the lacI repressor, and gene induction in by IPTG. HPLC methods have been developed that allow quantitation of virtually all of the metabolic intermediates in the cell pool.

  18. The Correlation of PPARα Activity and Cardiomyocyte Metabolism and Structure in Idiopathic Dilated Cardiomyopathy during Heart Failure Progression

    PubMed Central

    Czarnowska, E.; Domal-Kwiatkowska, D.; Reichman-Warmusz, E.; Bierla, J. B.; Sowinska, A.; Ratajska, A.; Goral-Radziszewska, K.; Wojnicz, R.

    2016-01-01

    This study aimed to define relationship between PPARα expression and metabolic-structural characteristics during HF progression in hearts with DCM phenotype. Tissue endomyocardial biopsy samples divided into three groups according to LVEF ((I) 45–50%, n = 10; (II) 30–40%, n = 15; (III) <30%, n = 15; and control (donor hearts, >60%, n = 6)) were investigated. The PPARα mRNA expression in the failing hearts was low in Group (I), high in Group (II), and comparable to that of the control in Group (III). There were analogous changes in the expression of FAT/CD36 and CPT-1 mRNA in contrast to continuous overexpression of GLUT-4 mRNA and significant increase of PDK-4 mRNA in Group (II). In addition, significant structural changes of cardiomyocytes with glycogen accumulation were accompanied by increased expression of PPARα. For the entire study population with HF levels of FAT/CD36 mRNA showed a strong tendency of negative correlation with LVEF. In conclusion, PPARα elevated levels may be a direct cause of adverse remodeling, both metabolic and structural. Thus, there is limited time window for therapy modulating cardiac metabolism and protecting cardiomyocyte structure in failing heart. PMID:26981112

  19. Improved methods for water shutoff. Final technical progress report, October 1, 1997--September 30, 1998

    SciTech Connect

    Seright, R.S.; Liang, J.T.; Schrader, R.; Hagstrom, J. II; Liu, J.; Wavrik, K.

    1998-10-01

    In the United States, more than 20 billion barrels of salt water are produced each year during oilfield operations. A tremendous economic incentive exists to reduce water production if that can be accomplished without significantly sacrificing hydrocarbon production. This three-year research project had three objectives. The first objective was to identify chemical blocking agents that will (a) during placement, flow readily through fractures without penetrating significantly into porous rock and with screening out or developing excessive pressure gradients and (b) at a predictable and controllable time, become immobile and resistant breakdown upon exposure to moderate to high pressure gradients. The second objective was to identify schemes that optimize placement of the above blocking agents. The third objective was to explain why gels and other chemical blocking agents reduce permeability to one phase (e.g., water) more than that to another phase (e.g., oil or gas). The authors also wanted to identify conditions that maximize this phenomenon. This project consisted of three tasks, each of which addressed one of the above objectives. This report describes work performed during the third and final period of the project. During this three-year project, they: (1) Developed a procedure and software for sizing gelant treatments in hydraulically fractured production wells; (2) Developed a method (based on interwell tracer results) to determine the potential for applying gel treatments in naturally fractured reservoirs; (3) Characterized gel properties during extrusion through fractures; (4) Developed a method to predict gel placement in naturally fractured reservoirs; (5) Made progress in elucidating the mechanism for why some gels can reduce permeability to water more than that to oil; (6) Demonstrated the limitations of using water/oil ratio diagnostic plots to distinguish between channeling and coning; and (7) Proposed a philosophy for diagnosing and attacking water

  20. Progress in the care of common inherited atherogenic disorders of apolipoprotein B metabolism.

    PubMed

    Ellis, Katrina L; Hooper, Amanda J; Burnett, John R; Watts, Gerald F

    2016-08-01

    Familial hypercholesterolaemia, familial combined hyperlipidaemia (FCH) and elevated lipoprotein(a) are common, inherited disorders of apolipoprotein B metabolism that markedly accelerate the onset of atherosclerotic cardiovascular disease (ASCVD). These disorders are frequently encountered in clinical lipidology and need to be accurately identified and treated in both index patients and their family members, to prevent the development of premature ASCVD. The optimal screening strategies depend on the patterns of heritability for each condition. Established therapies are widely used along with lifestyle interventions to regulate levels of circulating lipoproteins. New therapeutic strategies are becoming available, and could supplement traditional approaches in the most severe cases, but their long-term cost-effectiveness and safety have yet to be confirmed. We review contemporary developments in the understanding, detection and care of these highly atherogenic disorders of apolipoprotein B metabolism. PMID:27199287

  1. The Emerging Role of Disturbed CoQ Metabolism in Nonalcoholic Fatty Liver Disease Development and Progression

    PubMed Central

    Botham, Kathleen M.; Napolitano, Mariarosaria; Bravo, Elena

    2015-01-01

    Although non-alcoholic fatty liver disease (NAFLD), characterised by the accumulation of triacylglycerol in the liver, is the most common liver disorder, the causes of its development and progression to the more serious non-alcoholic steatohepatitis (NASH) remain incompletely understood. Oxidative stress has been implicated as a key factor in both these processes, and mitochondrial dysfunction and inflammation are also believed to play a part. Coenzyme Q (CoQ) is a powerful antioxidant found in all cell membranes which has an essential role in mitochondrial respiration and also has anti-inflammatory properties. NAFLD has been shown to be associated with disturbances in plasma and liver CoQ concentrations, but the relationship between these changes and disease development and progression is not yet clear. Dietary supplementation with CoQ has been found to be hepatoprotective and to reduce oxidative stress and inflammation as well as improving mitochondrial dysfunction, suggesting that it may be beneficial in NAFLD. However, studies using animal models or patients with NAFLD have given inconclusive results. Overall, evidence is now emerging to indicate that disturbances in CoQ metabolism are involved in NAFLD development and progression to NASH, and this highlights the need for further studies with human subjects to fully clarify its role. PMID:26633474

  2. The Emerging Role of Disturbed CoQ Metabolism in Nonalcoholic Fatty Liver Disease Development and Progression.

    PubMed

    Botham, Kathleen M; Napolitano, Mariarosaria; Bravo, Elena

    2015-12-01

    Although non-alcoholic fatty liver disease (NAFLD), characterised by the accumulation of triacylglycerol in the liver, is the most common liver disorder, the causes of its development and progression to the more serious non-alcoholic steatohepatitis (NASH) remain incompletely understood. Oxidative stress has been implicated as a key factor in both these processes, and mitochondrial dysfunction and inflammation are also believed to play a part. Coenzyme Q (CoQ) is a powerful antioxidant found in all cell membranes which has an essential role in mitochondrial respiration and also has anti-inflammatory properties. NAFLD has been shown to be associated with disturbances in plasma and liver CoQ concentrations, but the relationship between these changes and disease development and progression is not yet clear. Dietary supplementation with CoQ has been found to be hepatoprotective and to reduce oxidative stress and inflammation as well as improving mitochondrial dysfunction, suggesting that it may be beneficial in NAFLD. However, studies using animal models or patients with NAFLD have given inconclusive results. Overall, evidence is now emerging to indicate that disturbances in CoQ metabolism are involved in NAFLD development and progression to NASH, and this highlights the need for further studies with human subjects to fully clarify its role. PMID:26633474

  3. Apple Peel Supplemented Diet Reduces Parameters of Metabolic Syndrome and Atherogenic Progression in ApoE−/− Mice

    PubMed Central

    Gonzalez, Jaime; Donoso, Wendy; Sandoval, Nathalie; Reyes, María; Gonzalez, Priscila; Gajardo, Monica; Morales, Erik; Neira, Amalia; Razmilic, Iván; Yuri, José A.

    2015-01-01

    Cardiovascular Diseases (CVD) represent about 30% of all causes of death worldwide. The development of CVD is related in many cases with the previous existence of metabolic syndrome (MS). It is known that apple consumption has a cardiovascular protecting effect, containing phenolic compounds with antioxidant effect, which are concentrated in the fruit peel. The objective of this study was to test the effect of apple peel consumption in a murine model of MS and apoE−/− mice. Apple supplemented diets reduced the biochemical parameters (glycaemia, total cholesterol, HDL-cholesterol, LDL-cholesterol, ureic nitrogen, triglycerides, insulin, and asymmetric dimethylarginine (ADMA)) of MS model in CF1 mice significantly. The model apoE−/− mouse was used to evaluate the capacity of the apple peel to revert the progression of the atherogenesis. FD with HAP reverts cholesterol significantly and slows down the progression of the plate diminishing the cholesterol accumulation area. With these results, it can be concluded that the consumption of apple peel reduces several MS parameters and the atherogenic progression in mice. PMID:26075004

  4. Apple Peel Supplemented Diet Reduces Parameters of Metabolic Syndrome and Atherogenic Progression in ApoE-/- Mice.

    PubMed

    Gonzalez, Jaime; Donoso, Wendy; Sandoval, Nathalie; Reyes, María; Gonzalez, Priscila; Gajardo, Monica; Morales, Erik; Neira, Amalia; Razmilic, Iván; Yuri, José A; Moore-Carrasco, Rodrigo

    2015-01-01

    Cardiovascular Diseases (CVD) represent about 30% of all causes of death worldwide. The development of CVD is related in many cases with the previous existence of metabolic syndrome (MS). It is known that apple consumption has a cardiovascular protecting effect, containing phenolic compounds with antioxidant effect, which are concentrated in the fruit peel. The objective of this study was to test the effect of apple peel consumption in a murine model of MS and apoE-/- mice. Apple supplemented diets reduced the biochemical parameters (glycaemia, total cholesterol, HDL-cholesterol, LDL-cholesterol, ureic nitrogen, triglycerides, insulin, and asymmetric dimethylarginine (ADMA)) of MS model in CF1 mice significantly. The model apoE-/- mouse was used to evaluate the capacity of the apple peel to revert the progression of the atherogenesis. FD with HAP reverts cholesterol significantly and slows down the progression of the plate diminishing the cholesterol accumulation area. With these results, it can be concluded that the consumption of apple peel reduces several MS parameters and the atherogenic progression in mice. PMID:26075004

  5. D-erythroascorbic acid: Its preparations, chemistry, and metabolism (fungi and plants). Final report

    SciTech Connect

    Loewus, F.A.; Seib, P.A.

    1991-12-31

    The origin of oxalate in plants has received considerable attention and glycolate metabolism has been generally regarded as a prime precursor candidate although studies on the metabolism of L-ascorbic acid single out that plant constituent as well. Experiments with oxalate-accumulating plants that contain little or no tartaric acid revealed the presence of a comparable L-ascorbic acid metabolism with the exception that the cleavage products were oxalic acid and L-threonic acid or products of L-threonic acid metabolism. A reasonable mechanism for cleavage of L-ascorbic acid at the endiolic bond is found in studies on the photooxygenation of L-ascorbic acid. Presumably, analogs of L-ascorbic acid that differ only in the substituent at C4 also form a hydroperoxide in the presence of alkaline hydrogen peroxide and subsequently yield oxalic acid and the corresponding aldonic acid or its lactone. We became interested in such a possibility when we discovered that L-ascorbic acid was rare or absent in certain yeasts and fungi whereas a L-ascorbic acid analog, D-glycero-pent-2-enono- 1,4-lactone (D-erythroascorbic acid), was present. It has long been known that oxalate occurs in yeasts and fungi and its production plays a role in plant pathogenesis. As to the biosynthetic origin of fungal oxalic acid there is little information although it is generally assumed that oxaloacetate or possibly, glycolate, might be that precursor.

  6. Metabolism of proposed nerve agent pretreatment, pyridostigmine bromide. Final report, December 1995-December 1996

    SciTech Connect

    Leo, K.U.

    1996-12-01

    A reverse phase High Pressure Liquid Chromatography (HPLC) method was developed to separate pyridostigmine bromide from four potential metabolites. Using male and female microsomes from both rat and human, our data suggest that pyridostigmine bromide is not metabolized by the human live microsomes or DNA expressed human CYP-450s via direct observation of no metabolites being formed for incubations up to 90 minutes. Indirect evidence that pyridostigmine metabolism is not via the major human hepatic CYP-450s involved in drug metabolism, 1A2, 2C9, 2E1, 2D6, and 3A4, was observed by failure to inhibit these isozymes while co-incubated with substrates specific for those isozymes at concentrations of 2-3 times Km. The following CYP-450 substrates were co-incubated with pyridostigmine: phenacetin, tolbutamide, chlorzoxazone, bufuralol, and testosterone. Using unlabelled and 14C-pyridostigmine, metabolite formation was not observed in both male and female rat and human subcellular fractions, specifically cytosol and S9, or under conditions favoring human FMO activity (pH 8.3). These findings indicate the metabolism of pyridostigmine bromide is unlikely to be under any component of sexual dimorphism.

  7. Integration of Carbon, Nitrogen, and Oxygen Metabolism in Escherichia coli--Final Report

    SciTech Connect

    Rabinowitz, Joshua D; Wingreen, Ned s; Rabitz, Herschel A; Xu, Yifan

    2012-10-22

    A key challenge for living systems is balancing utilization of multiple elemental nutrients, such as carbon, nitrogen, and oxygen, whose availability is subject to environmental fluctuations. As growth can be limited by the scarcity of any one nutrient, the rate at which each nutrient is assimilated must be sensitive not only to its own availability, but also to that of other nutrients. Remarkably, across diverse nutrient conditions, E. coli grows nearly optimally, balancing effectively the conversion of carbon into energy versus biomass. To investigate the link between the metabolism of different nutrients, we quantified metabolic responses to nutrient perturbations using LC-MS based metabolomics and built differential equation models that bridge multiple nutrient systems. We discovered that the carbonaceous substrate of nitrogen assimilation, -ketoglutarate, directly inhibits glucose uptake and that the upstream glycolytic metabolite, fructose-1,6-bisphosphate, ultrasensitively regulates anaplerosis to allow rapid adaptation to changing carbon availability. We also showed that NADH controls the metabolic response to changing oxygen levels. Our findings support a general mechanism for nutrient integration: limitation for a nutrient other than carbon leads to build-up of the most closely related product of carbon metabolism, which in turn feedback inhibits further carbon uptake.

  8. Final 2004 Report on Adequate Yearly Progress in the Montgomery County Public Schools

    ERIC Educational Resources Information Center

    Stevenson, Jose W.

    2005-01-01

    The vast majority of Montgomery County public schools made sufficient progress on state testing and accountability standards in 2004 to comply with the adequate yearly progress (AYP) requirements under the "No Child Left Behind (NCLB) Act of 2001." Information released by the Maryland State Department of Education (MSDE) in October 2004 shows that…

  9. 40 CFR 62.15065 - How do I comply with the increment of progress for submittal of a final control plan?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....15065 How do I comply with the increment of progress for submittal of a final control plan? For your... 40 Protection of Environment 8 2010-07-01 2010-07-01 false How do I comply with the increment of progress for submittal of a final control plan? 62.15065 Section 62.15065 Protection of...

  10. Monitoring genetic and metabolic potential for in situ bioremediation: Mass spectrometry. 1997 annual progress report

    SciTech Connect

    Buchanan, M.V.; Hurst, G.B.; Britt, P.F.; McLuckey, S.A.; Doktycz, M.J.

    1997-09-01

    'A number of US Department of Energy (DOE) sites are contaminated with mixtures of dense non-aqueous phase liquids (DNAPLs) such as carbon tetrachloride, chloroform,. perchloroethylene, and trichloroethylene. At many of these sites, in situ microbial bioremediation is an attractive strategy for cleanup because it has the potential to degrade DNAPLs in situ without producing toxic byproducts. A rapid screening method to determine the broad range metabolic and genetic potential for contaminant degradation would greatly reduce the cost and time involved in assessment for in situ bioremediation as well as for monitoring ongoing bioremediation treatment. In this project, the ORNL Organic Mass Spectrometry (OMS) group is developing mass-spectrometry-based methods to screen for the genetic and metabolic potential for assessment and monitoring of in situ bioremediation of DNAPLs. In close collaboration, Professor Mary Lidstrom''s group at the University of Washington is identifying short DNA sequences related to microbial processes involved in the biodegradation of pollutants. This work will lay the foundation for development of a field-portable mass-spectrometry-based technique for rapid assessment and monitoring of bioremediation processes on site.'

  11. Metabolic therapy with Deanna Protocol supplementation delays disease progression and extends survival in amyotrophic lateral sclerosis (ALS) mouse model.

    PubMed

    Ari, Csilla; Poff, Angela M; Held, Heather E; Landon, Carol S; Goldhagen, Craig R; Mavromates, Nicholas; D'Agostino, Dominic P

    2014-01-01

    Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and eventual death from respiratory failure. There is currently no cure or effective treatment for ALS. Besides motor neuron degeneration, ALS is associated with impaired energy metabolism, which is pathophysiologically linked to mitochondrial dysfunction and glutamate excitotoxicity. The Deanna Protocol (DP) is a metabolic therapy that has been reported to alleviate symptoms in patients with ALS. In this study we hypothesized that alternative fuels in the form of TCA cycle intermediates, specifically arginine-alpha-ketoglutarate (AAKG), the main ingredient of the DP, and the ketogenic diet (KD), would increase motor function and survival in a mouse model of ALS (SOD1-G93A). ALS mice were fed standard rodent diet (SD), KD, or either diets containing a metabolic therapy of the primary ingredients of the DP consisting of AAKG, gamma-aminobutyric acid, Coenzyme Q10, and medium chain triglyceride high in caprylic triglyceride. Assessment of ALS-like pathology was performed using a pre-defined criteria for neurological score, accelerated rotarod test, paw grip endurance test, and grip strength test. Blood glucose, blood beta-hydroxybutyrate, and body weight were also monitored. SD+DP-fed mice exhibited improved neurological score from age 116 to 136 days compared to control mice. KD-fed mice exhibited better motor performance on all motor function tests at 15 and 16 weeks of age compared to controls. SD+DP and KD+DP therapies significantly extended survival time of SOD1-G93A mice by 7.5% (p = 0.001) and 4.2% (p = 0.006), respectively. Sixty-three percent of mice in the KD+DP and 72.7% of the SD+DP group lived past 125 days, while only 9% of the control animals survived past that point. Targeting energy metabolism with metabolic therapy produces a therapeutic effect in ALS mice which may prolong

  12. Metabolic Therapy with Deanna Protocol Supplementation Delays Disease Progression and Extends Survival in Amyotrophic Lateral Sclerosis (ALS) Mouse Model

    PubMed Central

    Ari, Csilla; Poff, Angela M.; Held, Heather E.; Landon, Carol S.; Goldhagen, Craig R.; Mavromates, Nicholas; D’Agostino, Dominic P.

    2014-01-01

    Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and eventual death from respiratory failure. There is currently no cure or effective treatment for ALS. Besides motor neuron degeneration, ALS is associated with impaired energy metabolism, which is pathophysiologically linked to mitochondrial dysfunction and glutamate excitotoxicity. The Deanna Protocol (DP) is a metabolic therapy that has been reported to alleviate symptoms in patients with ALS. In this study we hypothesized that alternative fuels in the form of TCA cycle intermediates, specifically arginine-alpha-ketoglutarate (AAKG), the main ingredient of the DP, and the ketogenic diet (KD), would increase motor function and survival in a mouse model of ALS (SOD1-G93A). ALS mice were fed standard rodent diet (SD), KD, or either diets containing a metabolic therapy of the primary ingredients of the DP consisting of AAKG, gamma-aminobutyric acid, Coenzyme Q10, and medium chain triglyceride high in caprylic triglyceride. Assessment of ALS-like pathology was performed using a pre-defined criteria for neurological score, accelerated rotarod test, paw grip endurance test, and grip strength test. Blood glucose, blood beta-hydroxybutyrate, and body weight were also monitored. SD+DP-fed mice exhibited improved neurological score from age 116 to 136 days compared to control mice. KD-fed mice exhibited better motor performance on all motor function tests at 15 and 16 weeks of age compared to controls. SD+DP and KD+DP therapies significantly extended survival time of SOD1-G93A mice by 7.5% (p = 0.001) and 4.2% (p = 0.006), respectively. Sixty-three percent of mice in the KD+DP and 72.7% of the SD+DP group lived past 125 days, while only 9% of the control animals survived past that point. Targeting energy metabolism with metabolic therapy produces a therapeutic effect in ALS mice which may

  13. 1H NMR Based Serum Metabolic Profiles Associated with Pathological Progression of Pancreatic Islet β Cell Tumor in Rip1-Tag2 Mice

    PubMed Central

    Yang, Yongxia; Liu, Ying; Zheng, Lingyun; Zhang, Qianqian; Gu, Quliang; Wang, Linlin; Wang, Lijing

    2015-01-01

    Pancreatic islet β cell tumor is the most common islet cell tumor. A well-characterized tumor progression in Rip1-Tag2 mice undergoes five stages, involving normal, hyperplasia, angiogenic islets, tumorigenesis and invasive carcinoma. 1H NMR based metabonomics was applied to identify potential biomarkers for monitoring pancreatic islet β cell tumor progression in Rip1-Tag2 mice. Multivariate analysis results showed the serum metabonome at hyperplasia stage shared the similar characteristics with the ones at normal stage as a result of slight proliferation of pancreatic islet β cells. At angiogenic islets stage, the up-regulated glycolysis, disturbed choline and phospholipid metabolism composed the metabolic signature. In addition to the changes mentioned above, several metabolites were identified as early biomarkers for tumorigenesis, including increased methionine, citrate and choline, and reduced acetate, taurine and glucose, which suggested the activated energy and amino acid metabolism. All the changes were aggravated at invasive carcinoma stage, coupled with notable changes in alanine, glutamate and glycine. Moreover, the distinct metabolic phenotype was found associated with the implanting of SV40 large T antigen in Rip1-Tag2 mice. The combined metabolic and multivariate statistics approach provides a robust method for screening the biomarkers of disease progression and examining the association between gene and metabolism. PMID:25892966

  14. The role of statins in preventing the progression of congestive heart failure in patients with metabolic syndrome.

    PubMed

    Fazio, Giovanni; Amoroso, Gisella Rita; Barbaro, Giuseppe; Novo, Giuseppina; Novo, Salvatore

    2008-01-01

    Heart Failure (CHF) is a very important public health problem in the world and certainly one of the most common debilitating diseases and cause of mortality. Current knowledge underlines that incidence rates are also influenced by the coexisting pathologic conditions that accelerate the development of disease or increase its severity. Important scientific evidence is emerging to demonstrate a strong correlation between HF and the metabolic syndrome (MetS). Hypolipemia-inducing medication offers the opportunity to discuss the possible existence of pharmacological substances that in addition to their specific targets have several demonstrated pleiotropic effects that could be beneficial in HF. Although several trials investigated statins treatment effects on HF in general, some evidence exists about the role that these drugs can have in the progression of the disease in the specific category of HF patients affected by MetS. In this review the possible positive effects of the statins treatment in this specific subset of patients are discussed. PMID:18991677

  15. The impact of RNA binding motif protein 4-regulated splicing cascade on the progression and metabolism of colorectal cancer cells

    PubMed Central

    Lin, Ying-Ju; Lin, Jung-Chun

    2015-01-01

    Dysregulated splicing of pre-messenger (m)RNA is considered a molecular occasion of carcinogenesis. However, the underlying mechanism is complex and remains to be investigated. Herein, we report that the upregulated miR-92a reduced the RNA-binding motif 4 (RBM4) protein expression, leading to the imbalanced expression of the neuronal polypyrimidine tract-binding (nPTB) protein through alternative splicing-coupled nonsense mediated decay (NMD) mechanism. Increase in nPTB protein enhances the relative level of fibroblast growth factor receptor 2 IIIc (FGFR2) and pyruvate kinase M2 (PKM2) transcripts which contribute to the progression and metabolic signature of CRC cells. Expression profiles of RBM4 and downstream alternative splicing events are consistently observed in cancerous tissues compared to adjacent normal tissues. These results constitute a mechanistic understanding of RBM4 on repressing the carcinogenesis of colorectal cells. PMID:26506517

  16. Response to diet-induced obesity produces time-dependent induction and progression of metabolic osteoarthritis in rat knees.

    PubMed

    Collins, Kelsey H; Hart, David A; Reimer, Raylene A; Seerattan, Ruth A; Herzog, Walter

    2016-06-01

    Obesity, and corresponding chronic-low grade inflammation, is associated with the onset and progression of knee OA. The origin of this inflammation is poorly understood. Here, the effect of high fat, high sucrose (HFS) diet induced obesity (DIO) on local (synovial fluid), and systemic (serum) inflammation is evaluated after a 12-week obesity induction and a further 16-week adaptation period. For 12-weeks of obesity induction, n = 40 DIO male Sprague-Dawley rats consumed a HFS diet while the control group (n = 14) remained on chow. DIO rats were allocated to prone (DIO-P, top 33% based on weight change) or resistant (DIO-R, bottom 33%) groups at 12-weeks. Animals were euthanized at 12- and after an additional 16-weeks on diet (28-weeks). At sacrifice, body composition and knee joints were collected and assessed. Synovial fluid and sera were profiled using cytokine array analysis. At 12-weeks, DIO-P animals demonstrated increased Modified Mankin scores compared to DIO-R and chow (p = 0.026), and DIO-R had higher Mankin scores compared to chow (p = 0.049). While numerous systemic and limited synovial fluid inflammatory markers were increased at 12-weeks in DIO animals compared to chow, by 28-weeks there were limited systemic differences but marked increases in local synovial fluid inflammatory marker concentrations. Metabolic OA may manifest from an initial systemic inflammatory disturbance. Twelve weeks of obesity induction leads to a unique inflammatory profile and induction of metabolic OA which is altered after a further 16-weeks of obesity and HFS diet intake, suggesting that obesity is a dynamic, progressive process. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1010-1018, 2016. PMID:26572064

  17. Pediatric non alcoholic fatty liver disease: old and new concepts on development, progression, metabolic insight and potential treatment targets

    PubMed Central

    2013-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in children. NAFLD has emerged to be extremely prevalent, and predicted by obesity and male gender. It is defined by hepatic fat infiltration >5% hepatocytes, in the absence of other causes of liver pathology. It includes a spectrum of disease ranging from intrahepatic fat accumulation (steatosis) to various degrees of necrotic inflammation and fibrosis (non-alcoholic steatohepatatis [NASH]). NAFLD is associated, in children as in adults, with severe metabolic impairments, determining an increased risk of developing the metabolic syndrome. It can evolve to cirrhosis and hepatocellular carcinoma, with the consequent need for liver transplantation. Both genetic and environmental factors seem to be involved in the development and progression of the disease, but its physiopathology is not yet entirely clear. In view of this mounting epidemic phenomenon involving the youth, the study of NAFLD should be a priority for all health care systems. This review provides an overview of current and new clinical-histological concepts of pediatric NAFLD, going through possible implications into patho-physiolocical and therapeutic perspectives. PMID:23530957

  18. Decreased Expression of Fructose-1,6-bisphosphatase Associates with Glucose Metabolism and Tumor Progression in Hepatocellular Carcinoma.

    PubMed

    Hirata, Hidenari; Sugimachi, Keishi; Komatsu, Hisateru; Ueda, Masami; Masuda, Takaaki; Uchi, Ryutaro; Sakimura, Shotaro; Nambara, Sho; Saito, Tomoko; Shinden, Yoshiaki; Iguchi, Tomohiro; Eguchi, Hidetoshi; Ito, Shuhei; Terashima, Kotaro; Sakamoto, Katsumi; Hirakawa, Masakazu; Honda, Hiroshi; Mimori, Koshi

    2016-06-01

    Fructose-1,6-bisphosphatase (FBP1), the rate-limiting enzyme in gluconeogenesis, is reduced in expression in certain cancers where it has been hypothesized to act as a tumor suppressor, including in hepatocellular carcinoma (HCC). Here, we report functional evidence supporting this hypothesis, providing a preclinical rationale to develop FBP1 as a therapeutic target for HCC treatment. Three independent cohorts totaling 594 cases of HCC were analyzed to address clinical significance. Lower FBP1 expression associated with advanced tumor stage, poor overall survival, and higher tumor recurrence rates. In HCC cell lines, where endogenous FBP1 expression is low, engineering its ectopic overexpression inhibited tumor growth and intracellular glucose uptake by reducing aerobic glycolysis. In patient specimens, promoter methylation and copy-number loss of FBP1 were independently associated with decreased FBP1 expression. Similarly, FBP1 downregulation in HCC cell lines was also associated with copy-number loss. HCC specimens exhibiting low expression of FBP1 had a highly malignant phenotype, including large tumor size, poor differentiation, impaired gluconeogenesis, and enhanced aerobic glycolysis. The effects of FBP1 expression on prognosis and glucose metabolism were confirmed by gene set enrichment analysis. Overall, our findings established that FBP1 downregulation in HCC contributed to tumor progression and poor prognosis by altering glucose metabolism, and they rationalize further study of FBP1 as a prognostic biomarker and therapeutic target in HCC patients. Cancer Res; 76(11); 3265-76. ©2016 AACR. PMID:27197151

  19. The increased level of COX-dependent arachidonic acid metabolism in blood platelets from secondary progressive multiple sclerosis patients.

    PubMed

    Morel, Agnieszka; Miller, Elzbieta; Bijak, Michal; Saluk, Joanna

    2016-09-01

    Platelet activation is increasingly postulated as a possible component of the pathogenesis of multiple sclerosis (MS), especially due to the increased risk of cardiovascular events in MS. Arachidonic acid cascade metabolized by cyclooxygenase (COX) is a key pathway of platelet activation. The aim of our study was to investigate the COX-dependent arachidonic acid metabolic pathway in blood platelets from secondary progressive multiple sclerosis (SP MS) patients. The blood samples were obtained from 50 patients (man n = 22; female n = 28), suffering from SP MS, diagnosed according to the revised McDonald criteria. Platelet aggregation was measured in platelet-rich plasma after arachidonic acid stimulation. The level of COX activity and thromboxane B2 concentration were determined by ELISA method. Lipid peroxidation was assessed by measuring the level of malondialdehyde. The results were compared with a control group of healthy volunteers. We found that blood platelets obtained from SP MS patients were more sensitive to arachidonic acid and their response measured as platelet aggregation was stronger (about 14 %) relative to control. We also observed a significantly increased activity of COX (about 40 %) and synthesis of thromboxane B2 (about 113 %). The generation of malondialdehyde as a marker of lipid peroxidation was about 10 % higher in SP MS than in control. Cyclooxygenase-dependent arachidonic acid metabolism is significantly increased in blood platelets of patients with SP MS. Future clinical studies are required to recommend the use of low-dose aspirin, and possibly other COX inhibitors in the prevention of cardiovascular risk in MS. PMID:27507559

  20. Progress in drug development for Alzheimer's disease: An overview in relation to mitochondrial energy metabolism.

    PubMed

    Hroudová, Jana; Singh, Namrata; Fišar, Zdeněk; Ghosh, Kallol K

    2016-10-01

    Current possibilities of Alzheimer's disease (AD) treatment are very limited and are based on administration of cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and/or N-methyl-d-aspartate receptor antagonist, memantine. Newly synthesized drugs affect multiple AD pathophysiological pathways and can act as inhibitors of cholinesterases (AChE, BuChE), inhibitors of monoamine oxidases (MAO-A, MAO-B), modulators of mitochondrial permeability transition pores, modulators of amyloid-beta binding alcohol dehydrogenase and antioxidants. Effects of clinically used as well as newly developed AD drugs were studied in relation to energy metabolism and mitochondrial functions, including oxidative phosphorylation, activities of enzymes of citric acid cycle or electron transfer system, mitochondrial membrane potential, calcium homeostasis, production of reactive oxygen species and MAO activity. PMID:27094132

  1. [Regulation of terpene metabolism]. Annual progress report, March 15, 1989--March 14, 1990

    SciTech Connect

    Croteau, R.

    1989-11-09

    Terpenoid oils, resins, and waxes from plants are important renewable resources. The objective of this project is to understand the regulation of terpenoid metabolism using the monoterpenes (C{sub 10}) as a model. The pathways of monoterpene biosynthesis and catabolism have been established, and the relevant enzymes characterized. Developmental studies relating enzyme levels to terpene accumulation within the oil gland sites of synthesis, and work with bioregulators, indicate that monoterpene production is controlled by terpene cyclases, the enzymes catalyzing the first step of the monoterpene pathway. As the leaf oil glands mature, cyclase levels decline and monoterpene biosynthesis ceases. Yield then decreases as the monoterpenes undergo catabolism by a process involving conversion to a glycoside and transport from the leaf glands to the root. At this site, the terpenoid is oxidatively degraded to acetate that is recycled into other lipid metabolites. During the transition from terpene biosynthesis to catabolism, the oil glands undergo dramatic ultrastructural modification. Degradation of the producing cells results in mixing of previously compartmentized monoterpenes with the catabolic enzymes, ultimately leading to yield decline. This regulatory model is being applied to the formation of other terpenoid classes (C{sub 15} C{sub 20}, C{sub 30}, C{sub 40}) within the oil glands. Preliminary investigations on the formation of sesquiterpenes (C{sub 15}) suggest that the corresponding cyclases may play a lesser role in determining yield of these products, but that compartmentation effects are important. From these studies, a comprehensive scheme for the regulation of terpene metabolism is being constructed. Results from this project wail have important consequences for the yield and composition of terpenoid natural products that can be made available for industrial exploitation.

  2. Altered intramuscular lipid metabolism relates to diminished insulin action in men, but not women, in progression to diabetes.

    PubMed

    Perreault, Leigh; Bergman, Bryan C; Hunerdosse, Devon M; Eckel, Robert H

    2010-11-01

    Whether sex differences in intramuscular triglyceride (IMTG) metabolism underlie sex differences in the progression to diabetes are unknown. Therefore, the current study examined IMTG concentration and fractional synthesis rate (FSR) in obese men and women with normal glucose tolerance (NGT) vs. those with prediabetes (PD). PD (n = 13 men and 7 women) and NGT (n = 7 men and 12 women) groups were matched for age and anthropometry. Insulin action was quantified using a hyperinsulinemic-euglycemic clamp with infusion of [6,6-(2)H(2)]-glucose. IMTG concentration was measured by gas chromatography/mass spectrometry (GC/MS) and FSR by GC/combustion isotope ratio MS (C-IRMS), from muscle biopsies taken after infusion of [U-(13)C]palmitate during 4 h of rest. In PD men, the metabolic clearance rate (MCR) of glucose was lower during the clamp (4.71 ± 0.77 vs. 8.62 ± 1.26 ml/kg fat-free mass (FFM)/min, P = 0.04; with a trend for lower glucose rate of disappearance (Rd), P = 0.07), in addition to higher IMTG concentration (41.2 ± 5.0 vs. 21.2 ± 3.4 µg/mg dry weight, P ≤ 0.01), lower FSR (0.21 ± 0.03 vs. 0.42 ± 0.06 %/h, P ≤ 0.01), and lower oxidative capacity (P = 0.03) compared to NGT men. In contrast, no difference in Rd, IMTG concentration, or FSR was seen in PD vs. NGT women. Surprisingly, glucose Rd during the clamp was not different between NGT men and women (P = 0.25) despite IMTG concentration being higher (42.6 ± 6.1 vs. 21.2 ± 3.4 µg/mg dry weight, P = 0.03) and FSR being lower (0.23 ± 0.04 vs. 0.42 ± 0.06 %/h, P = 0.02) in women. Alterations in IMTG metabolism relate to diminished insulin action in men, but not women, in the progression toward diabetes. PMID:20379150

  3. [Regulation of terpene metabolism]. Annual progress report, March 15, 1990--March 14, 1991

    SciTech Connect

    Croteau, R.

    1991-12-31

    During the last grant period, we have completed studies on the key pathways of monoterpene biosynthesis and catabolism in sage and peppermint, and have, by several lines of evidence, deciphered the rate-limiting step of each pathway. We have at least partially purified and characterized the relevant enzymes of each pathway. We have made a strong case, based on analytical, in vivo, and in vitro studies, that terpene accumulation depends upon the balance between biosynthesis and catabolism, and provided supporting evidence that these processes are developmentally-regulated and very closely associated with senescence of the oil glands. Oil gland ontogeny has been characterized at the ultrastructural level. We have exploited foliar-applied bioregulators to delay gland senescence, and have developed tissue explant and cell culture systems to study several elusive aspects of catabolism. We have isolated pure gland cell clusters and localized monoterpene biosynthesis and catabolism within these structures, and have used these preparations as starting materials for the purification to homogeneity of target ``regulatory`` enzymes. We have thus developed the necessary background knowledge, based on a firm understanding of enzymology, as well as the necessary experimental tools for studying the regulation of monoterpene metabolism at the molecular level. Furthermore, we are now in a position to extend our systematic approach to other terpenoid classes (C{sub 15}-C{sub 30}) produced by oil glands.

  4. Recent Progress on Bile Acid Receptor Modulators for Treatment of Metabolic Diseases.

    PubMed

    Xu, Yanping

    2016-07-28

    Bile acids are steroid-derived molecules synthesized in the liver, secreted from hepatocytes into the bile canaliculi, and subsequently stored in the gall bladder. During the feeding, bile flows into the duodenum, where it contributes to the solubilization and digestion of lipid-soluble nutrients. After a meal, bile-acid levels increase in the intestine, liver, and also in the systemic circulation. Therefore, serum bile-acid levels serve as an important sensing mechanism for nutrient and energy. Recent studies have described bile acids as versatile signaling molecules endowed with systemic endocrine functions. Bile acids are ligands for G-protein coupled receptors (GPCRs) such as TGR5 (also known as GPBAR1, M-BAR, and BG37) and nuclear hormone receptors including farnesoid X receptor (FXR; also known as NR1H4). Acting through these diverse signaling pathways, bile acids regulate triglyceride, cholesterol, glucose homeostasis, and energy expenditure. These bile-acid-controlled signaling pathways have become the source of promising novel drug targets to treat common metabolic and hepatic diseases. PMID:26878262

  5. Anti-microRNA-21 oligonucleotides prevent Alport nephropathy progression by stimulating metabolic pathways.

    PubMed

    Gomez, Ivan G; MacKenna, Deidre A; Johnson, Bryce G; Kaimal, Vivek; Roach, Allie M; Ren, Shuyu; Nakagawa, Naoki; Xin, Cuiyan; Newitt, Rick; Pandya, Shweta; Xia, Tai-He; Liu, Xueqing; Borza, Dorin-Bogdan; Grafals, Monica; Shankland, Stuart J; Himmelfarb, Jonathan; Portilla, Didier; Liu, Shiguang; Chau, B Nelson; Duffield, Jeremy S

    2015-01-01

    MicroRNA-21 (miR-21) contributes to the pathogenesis of fibrogenic diseases in multiple organs, including the kidneys, potentially by silencing metabolic pathways that are critical for cellular ATP generation, ROS production, and inflammatory signaling. Here, we developed highly specific oligonucleotides that distribute to the kidney and inhibit miR-21 function when administered subcutaneously and evaluated the therapeutic potential of these anti-miR-21 oligonucleotides in chronic kidney disease. In a murine model of Alport nephropathy, miR-21 silencing did not produce any adverse effects and resulted in substantially milder kidney disease, with minimal albuminuria and dysfunction, compared with vehicle-treated mice. miR-21 silencing dramatically improved survival of Alport mice and reduced histological end points, including glomerulosclerosis, interstitial fibrosis, tubular injury, and inflammation. Anti-miR-21 enhanced PPARα/retinoid X receptor (PPARα/RXR) activity and downstream signaling pathways in glomerular, tubular, and interstitial cells. Moreover, miR-21 silencing enhanced mitochondrial function, which reduced mitochondrial ROS production and thus preserved tubular functions. Inhibition of miR-21 was protective against TGF-β-induced fibrogenesis and inflammation in glomerular and interstitial cells, likely as the result of enhanced PPARα/RXR activity and improved mitochondrial function. Together, these results demonstrate that inhibition of miR-21 represents a potential therapeutic strategy for chronic kidney diseases including Alport nephropathy. PMID:25415439

  6. Anti–microRNA-21 oligonucleotides prevent Alport nephropathy progression by stimulating metabolic pathways

    PubMed Central

    Gomez, Ivan G.; MacKenna, Deidre A.; Johnson, Bryce G.; Kaimal, Vivek; Roach, Allie M.; Ren, Shuyu; Nakagawa, Naoki; Xin, Cuiyan; Newitt, Rick; Pandya, Shweta; Xia, Tai-He; Liu, Xueqing; Borza, Dorin-Bogdan; Grafals, Monica; Shankland, Stuart J.; Himmelfarb, Jonathan; Portilla, Didier; Liu, Shiguang; Chau, B. Nelson; Duffield, Jeremy S.

    2014-01-01

    MicroRNA-21 (miR-21) contributes to the pathogenesis of fibrogenic diseases in multiple organs, including the kidneys, potentially by silencing metabolic pathways that are critical for cellular ATP generation, ROS production, and inflammatory signaling. Here, we developed highly specific oligonucleotides that distribute to the kidney and inhibit miR-21 function when administered subcutaneously and evaluated the therapeutic potential of these anti–miR-21 oligonucleotides in chronic kidney disease. In a murine model of Alport nephropathy, miR-21 silencing did not produce any adverse effects and resulted in substantially milder kidney disease, with minimal albuminuria and dysfunction, compared with vehicle-treated mice. miR-21 silencing dramatically improved survival of Alport mice and reduced histological end points, including glomerulosclerosis, interstitial fibrosis, tubular injury, and inflammation. Anti–miR-21 enhanced PPARα/retinoid X receptor (PPARα/RXR) activity and downstream signaling pathways in glomerular, tubular, and interstitial cells. Moreover, miR-21 silencing enhanced mitochondrial function, which reduced mitochondrial ROS production and thus preserved tubular functions. Inhibition of miR-21 was protective against TGF-β–induced fibrogenesis and inflammation in glomerular and interstitial cells, likely as the result of enhanced PPARα/RXR activity and improved mitochondrial function. Together, these results demonstrate that inhibition of miR-21 represents a potential therapeutic strategy for chronic kidney diseases including Alport nephropathy. PMID:25415439

  7. Metabolism leaves its mark on the powerhouse: recent progress in post-translational modifications of lysine in mitochondria

    PubMed Central

    Papanicolaou, Kyriakos N.; O'Rourke, Brian; Foster, D. Brian

    2014-01-01

    Lysine modifications have been studied extensively in the nucleus, where they play pivotal roles in gene regulation and constitute one of the pillars of epigenetics. In the cytoplasm, they are critical to proteostasis. However, in the last decade we have also witnessed the emergence of mitochondria as a prime locus for post-translational modification (PTM) of lysine thanks, in large measure, to evolving proteomic techniques. Here, we review recent work on evolving set of PTM that arise from the direct reaction of lysine residues with energized metabolic thioester-coenzyme A intermediates, including acetylation, succinylation, malonylation, and glutarylation. We highlight the evolutionary conservation, kinetics, stoichiometry, and cross-talk between members of this emerging family of PTMs. We examine the impact on target protein function and regulation by mitochondrial sirtuins. Finally, we spotlight work in the heart and cardiac mitochondria, and consider the roles acetylation and other newly-found modifications may play in heart disease. PMID:25228883

  8. FY08 LDRD Final Report Probabilistic Inference of Metabolic Pathways from Metagenomic Sequence Data

    SciTech Connect

    D'haeseleer, P

    2009-03-01

    Metagenomic 'shotgun' sequencing of environmental microbial communities has the potential to revolutionize microbial ecology, allowing a cultivation-independent, yet sequence-based analysis of the metabolic capabilities and functions present in an environmental sample. Although its intensive sequencing requirements are a good match for the continuously increasing bandwidth at sequencing centers, the complexity, seemingly inexhaustible novelty, and 'scrambled' nature of metagenomic data is also proving a tremendous challenge for analysis. In fact, many metagenomics projects do not go much further than providing a list of novel gene variants and over- or under-represented functional gene categories. In this project, we proposed to develop a set of novel metagenomic sequence analysis tools, including a binning method to group sequences by species, inference of phenotypes and metabolic pathways from these reconstructed species, and extraction of coarse-grained flux models. We proposed to closely collaborate with the DOE Joint Genome Institute to align these tools with their metagenomics analysis needs and the developing IMG/M metagenomics pipeline. Results would be cross-validated with simulated metagenomic data using a testing platform developed at the JGI.

  9. A Report on Early State and Local Progress towards WIA Implementation. Final Interim Report.

    ERIC Educational Resources Information Center

    D'Amico, Ronald; Kogan, Deborah; Kreutzer, Suzanne; Wiegand, Andrew; Baker, Alberta; Carrick, Gardner; McCarthy, Carole

    Early state and local progress toward implementation of the Workforce Investment Act of 1998 (WIA) was reviewed. Data were collected through visits to selected sites in Florida, Kentucky, Pennsylvania, Texas, Utah, and Vermont and a 90-item Workforce System Information and Evaluation (WSIE) data collection form. The following aspects of WIA…

  10. Development of Career Progression Systems for Employees in the Foodservice Industry. Final Report.

    ERIC Educational Resources Information Center

    National Restaurant Association, Chicago, IL.

    Firms representing four segments of the foodservice industry (institutional foodservice (9 jobs), commercial restaurants (19 jobs), hotel foodservice (100 jobs), and airline foodservice (10 jobs), participated in a career and training study to test the feasibility of designing and implementing career progression (c.p.) systems within these…

  11. Seminar on Foci for Progress in Scientific Publications: A Summary and Final Report.

    ERIC Educational Resources Information Center

    Battelle Memorial Inst., Columbus, OH.

    A one-day seminar was convened on November 4, 1969, to consider problems involved in communicating scientific information and the progress that has been made in improving the scientific publication mechanism. Thirty participants representing different types of information producers, users, and organizations contributed to the seminar discussion.…

  12. Slow Progress In Finalizing Measles And Rubella Elimination In The European Region.

    PubMed

    Biellik, Robin; Davidkin, Iria; Esposito, Susanna; Lobanov, Andrey; Kojouharova, Mira; Pfaff, Günter; Santos, José Ignacio; Simpson, John; Mamou, Myriam Ben; Butler, Robb; Deshevoi, Sergei; Huseynov, Shahin; Jankovic, Dragan; Shefer, Abigail

    2016-02-01

    All countries in the World Health Organization European Region committed to eliminating endemic transmission of measles and rubella by 2015, and disease incidence has decreased dramatically. However, there was little progress between 2012 and 2013, and the goal will likely not be achieved on time. Genuine political commitment, increased technical capacity, and greater public awareness are urgently needed, especially in Western Europe. PMID:26858387

  13. [Studies of the fundamental nature of catalytic acidity, sites and intermediates]: Final performance (technical progress) report

    SciTech Connect

    Not Available

    1993-12-31

    This project was concerned with the fundamental nature of catalyst acidity in the H-zeolites and silica/alumina cracking catalysts. This report summarizes the progress on this project over the past five years. The titles of the twelve papers generated by this research are provided in the attached bibliography in chronological order.

  14. The progression from a lower to a higher invasive stage of bladder cancer is associated with severe alterations in glucose and pyruvate metabolism

    SciTech Connect

    Conde, Vanessa R.; Oliveira, Pedro F.; Ramalhosa, Elsa; Pereira, José A.; Alves, Marco G.; Silva, Branca M.

    2015-07-01

    Cancer cells present a particular metabolic behavior. We hypothesized that the progression of bladder cancer could be accompanied by changes in cells glycolytic profile. We studied two human bladder cancer cells, RT4 and TCCSUP, in which the latter represents a more invasive stage. The levels of glucose, pyruvate, alanine and lactate in the extracellular media were measured by Proton Nuclear Magnetic Resonance. The protein expression levels of glucose transporters 1 (GLUT1) and 3 (GLUT3), monocarboxylate transporter 4 (MCT4), phosphofructokinase-1 (PFK1), glutamic-pyruvate transaminase (GPT) and lactate dehydrogenase (LDH) were determined. Our data showed that glucose consumption and GLUT3 levels were similar in both cell lines, but TCCSUP cells displayed lower levels of GLUT1 and PFK expression. An increase in pyruvate consumption, concordant with the higher levels of lactate and alanine production, was also detected in TCCSUP cells. Moreover, TCCSUP cells presented lower protein expression levels of GPT and LDH. These results illustrate that bladder cancer progression is associated with alterations in cells glycolytic profile, namely the switch from glucose to pyruvate consumption in the more aggressive stage. This may be useful to develop new therapies and to identify biomarkers for cancer progression. - Highlights: • Metabolic phenotype of less and high invasive bladder cancer cells was studied. • Bladder cancer progression involves alterations in cells glycolytic profile. • More invasive bladder cancer cells switch from glucose to pyruvate consumption. • Our results may help to identify metabolic biomarkers of bladder cancer progression.

  15. Metabolic Syndrome and Prostate Cancer: a Review of Complex Interplay Amongst Various Endocrine Factors in the Pathophysiology and Progression of Prostate Cancer.

    PubMed

    Rhee, Handoo; Vela, Ian; Chung, Eric

    2016-04-01

    The human prostate gland is an endocrine organ where dysregulation of various hormonal factors may play a pivotal role in the pathogenesis of prostate cancer. There is emerging epidemiological data to support the role of components of metabolic syndrome, namely, obesity, hypercholesterolaemia, diabetes and hyperinsulinaemia on the development and/or the progression of prostate cancer. Although the exact mechanisms behind the relationship between metabolic syndrome and prostate cancer remain largely unknown, various in vitro and animal experiments of metabolic syndrome models have been shown to promote survival, mitogenesis, metastasis and treatment resistance pathways, through various adaptive responses such as intracellular steroidogenesis and lipogenesis. Also, in a large proportion of men with metabolic syndrome, alteration in levels of hormones such as testosterone, leptin and adiponectin has been shown to contribute towards the aggression of prostate cancer. Whilst the exact bio-pathophysiological mechanisms between metabolic syndrome and prostate cancer are yet to be fully elucidated, medications that target specific components of metabolic syndrome have further provided evidence for the inter-relationship between metabolic syndrome, its components and prostate cancer. Emerging in vitro and molecular data is likely to bring us closer to utilizing this knowledge to target particular cancer survival pathways and improving outcomes for men with prostate cancer. PMID:26546071

  16. Metabolism of hydrazine. Final report 1 Oct 79-30 Sep 80. [Rats

    SciTech Connect

    Dost, F.N.; Broderick, D.J.; Krivak, B.M.; Reed, D.J.

    1981-06-01

    In rats exposed to atmospheric hydrazine, the log of blood hydrazine concentration was found to bear a more or less linear relation to atmospheric hydrazine levels. At 20-25 mg hydrazine/cu M, blood concentrations approached 100 nmole/ml, and were about 2 nmole/ml at atmospheric concentrations of about 3 mg/cu M. During exposure, blood concentrations tended to rise rather quickly in the first hour, then oscillated slowly around a generally constant level throughout six hours of exposure. Blood concentration of hydrazine following a single 1 nmole/kg dose decreased with a first phase halftime of about 45 minutes followed by a slower decrease with halftime of 27 hours. Less than one percent of such doses was excreted in bile. In vitro reaction of 5 m molar hydrazine in whole blood proceeded at a rate of about .016 micromole/m1/minute or about 10% in 30 minutes. With higher concentrations turnover becomes more rapid and can exceed the hemoglobin subunit equivalence by many fold. Extensive efforts to locate 15N/labelled urinary metabolities that would account for remaining uninventoried hydrazine have not yet succeeded.

  17. 2001 Gordon Research Conference on Applied and Environmental Microbiology. Final progress report [agenda and attendee list

    SciTech Connect

    Drake, Harold

    2001-07-26

    The Gordon Research Conference on Applied and Environmental Microbiology was held at Connecticut College, New London, Connecticut, July 22-27, 2001. The conference was attended by 121 participants. The attendees represented the spectrum of endeavor in this field, coming from academia, industry, and government laboratories, and included US and foreign scientists, senior researchers, young investigators, and students. Emphasis was placed on current unpublished research and discussion of the future target areas in this field. There was a conscious effort to stimulate discussion about the key issues in the field today. Session topics included the following: Environmental and applied genomics, Cell-to-cell signaling and multicellular behavior, Emerging technologies and methods, Novel metabolisms and ecosystems, Directed evolution of enzymes and pathways, Symbiotic and trophic relationships, Synthesis and application of novel biopolymers, and Microbes at the oxic-anoxic interface. There was also a special lecture titled ''Under the umbrella of the big tree: microbial biology into the 21st century.''

  18. Genetics of thermophilic bacteria. Final progress report, May 1, 1984--April 30, 1991

    SciTech Connect

    Welker, N.E.

    1991-12-31

    Organisms adapted to high temperature have evolved a variety of unique solutions to the biochemical problems imposed by this environment. Adaptation is commonly used to describe the biochemical properties of organisms which have become adapted to their environment (genetic adaptation). It can also mean the direct response-at the cellular level-of an organism to changes in temperature (physiological adaptation). Thermophilic bacilli (strains of Bacillus stearothermophilus) can exhibit a variety of biochemical adaptations in response to changes in temperature. These include changes in the composition and stability of the membrane, metabolic potential, the transport of amino acids, regulatory mechanisms, ribose methylation of tRNA, protein thermostability, and nutritional requirements. The objectives of the research were to develop efficient and reliable genetic systems to analyze and manipulate B. Stearothermophilus, and to use these systems initiate a biochemical, molecular, and genetic investigations of genes that are required for growth at high temperature.

  19. [Experimental and theoretical plasma physics program]. [Final progress report, 1982--1983

    SciTech Connect

    Griem, H.

    1983-12-31

    In recent years, members of the Maryland Theory Group have made significant contributions to the national fusion theory programs, and, in many cases, these theoretical developments helped to interpret experimental results and to design new experimental programs. In the following, the authors summarize the technical progress in five major areas: (1) RF interaction with plasmas including wave propagation and RF heating, (2) spheromak formation, equilibrium, and stability; (3) stability of nonaxisymmetric systems (EBT, mirrors, etc.); (4) stability theory of toroidal plasmas (tokamak, RFP, etc); and (5) nonlinear theory.

  20. Intermolecular potential functions and high resolution molecular spectroscopy of weakly bound complexes. Final progress report

    SciTech Connect

    Muenter, J.S.

    1997-04-01

    This report describes accomplishments over the past year in research supported by this grant. Two papers published in this period are briefly discussed. The general goal of the work is to consolidate the understanding of experimental results through a theoretical model of intermolecular potential energy surfaces. Progress in the experimental and theoretical phases of the program are presented and immediate goals outlined. The ability to construct analytic intermolecular potential functions that accurately predict the energy of interaction between small molecules will have great impact in many areas of chemistry, biochemistry, and biology.

  1. Experimental Program Final Technical Progress Report: 15 February 2007 to 30 September 2012

    SciTech Connect

    Kinney, Edward R.

    2014-09-12

    This is the final technical report of the grant DE-FG02-04ER41301 to the University of Colorado at Boulder entitled "Intermediate Energy Nuclear Physics" and describes the results of our funded activities during the period 15 February 2007 to 30 September 2012. These activities were primarily carried out at Fermilab, RHIC, and the German lab DESY. Significant advances in these experiments were carried out by members of the Colorado group and are described in detail.

  2. Gasoline from natural gas by sulfur processing. Quarterly progress report, January 1994--March 1994, final version

    SciTech Connect

    Erekson, E.J.; Miao, F.Q.

    1994-06-01

    This report presents the work performed at the Institute of Gas Technology (IGT) during the third program quarter from January 1, 1994 to March 31, 1994, under Department of Energy (DOE) Contract No. DE-AC22-93PC92114. This program has coordinated funding for Task I from IGT`s Sustaining Membership Program(SMP), while DOE is funding Tasks 2 through 8. Progress in all tasks is reported here. The overall objective of this research project is to develop a catalytic process to convert natural gas to liquid transportation fuels. The process consists of two steps that each utilize catalysts and sulfur containing intermediates: (1) to convert natural gas to CS{sub 2}, and (2) to convert CS{sub 2} to gasoline range liquids. Experimental data will be generated to demonstrate the potential of catalysts and the overall process. During this quarter, progress in the following areas has been made. Five catalysts for step I have been prepared. A total of thirty runs with catalysts, IGT-MS-103 and IGT-MS-105, were performed. At 5 seconds residence time and above 1000 {degrees}C the hydrogen sulfide decomposition approached equilibrium. H{sub 2}S conversion was 80% at 1131 {degrees}C. A total of fourteen runs were performed for carbon deposition/regeneration studies. Six catalysts as well as quartz wool were used in these studies. During the methane decomposition runs, carbon formation was found on the catalyst surface. During the subsequent hydrogen sulfide regeneration runs, a significant amount of carbon disulfide was detected in the product stream. Equilibrium calculations for the reaction of carbon with sulfur and with hydrogen sulfide were also performed in this quarter. At 1227{degrees}C, 1 atm, as high as 80% carbon conversion can be obtained at equilibrium.

  3. Progress Report for DOE FG02-08ER64510 (Final, April 2014)

    SciTech Connect

    Dunn, Robert

    2014-04-01

    Over the course of five years we have established a long-term array of warming chambers at Duke and Harvard Forest that simulate future conditions with regard to temperature. In these chambers, we have studied, ants, other animal taxa, fungi, bacteria and plants and their responses to the treatments. We have coupled these studies with lab experiments, large-scale observations, and models to contextualize our results. Finally, we have developed integrative models of the future distribution of species and their consequences as a result of warming in eastern North America and more generally.

  4. [Tampa Electric Company IGCC project]. Final public design report; Technical progress report

    SciTech Connect

    1996-07-01

    This final Public Design Report (PDR) provides completed design information about Tampa Electric Company`s Polk Power Station Unit No. 1, which will demonstrate in a commercial 250 MW unit the operating parameters and benefits of the integration of oxygen-blown, entrained-flow coal gasification with advanced combined cycle technology. Pending development of technically and commercially viable sorbent for the Hot Gas Cleanup System, the HGCU also is demonstrated. The report is organized under the following sections: design basis description; plant descriptions; plant systems; project costs and schedule; heat and material balances; general arrangement drawings; equipment list; and miscellaneous drawings.

  5. Final Progress Report: Coupled Biogeochemical Process Evaluation for Conceptualizing Trichloroethylene Cometabolism

    SciTech Connect

    Crawford, Ronald L; Paszczynski, Andrzej J

    2010-02-19

    Our goal within the overall project is to demonstrate the presence and abundance of methane monooxygenases (MMOs) enzymes and their genes within the microbial community of the Idaho National Laboratory (INL) Test Area North (TAN) site. MMOs are thought to be the primary catalysts of natural attenuation of trichloroethylene (TCE) in contaminated groundwater at this location. The actual presence of the proteins making up MMO complexes would provide direct evidence for its participation in TCE degradation. The quantitative estimation of MMO genes and their translation products (sMMO and pMMO proteins) and the knowledge about kinetics and substrate specificity of MMOs will be used to develop mathematical models of the natural attenuation process in the TAN aquifer. The model will be particularly useful in prediction of TCE degradation rate in TAN and possibly in the other DOE sites. Bacteria known as methanotrophs produce a set of proteins that assemble to form methane monooxygenase complexes (MMOs), enzymes that oxidize methane as their natural substrate, thereby providing a carbon and energy source for the organisms. MMOs are also capable of co-metabolically transforming chlorinated solvents like TCE into nontoxic end products such as carbon dioxide and chloride. There are two known forms of methane monooxygenase, a membrane-bound particulate form (pMMO) and a cytoplasmic soluble form (sMMO). pMMO consists of two components, pMMOH (a hydroxylase comprised of 47-, 27-, and 24-kDa subunits) and pMMOR (a reductase comprised of 63 and 8-kDa subunits). sMMO consists of three components: a hydroxylase (protein A-250 kDa), a dimer of three subunits (α2β2γ2), a regulatory protein (protein B-15.8 kDa), and a reductase (protein C-38.6 kDa). All methanotrophs will produce a methanol dehydrogenase to channel the product of methane oxidation (methanol) into the central metabolite formaldehyde. University of Idaho (UI) efforts focused on proteomic analyses using mass

  6. Development of a Coal Quality Expert. Final technical progress report No. 14, [July--September 1993

    SciTech Connect

    Not Available

    1994-01-17

    This is the fourteenth Technical Progress Report, describing work performed under DOE Contract No. DE-FC22-90PC89663, ``Development of a Coal Quality Expert.`` The contract is a Cooperative Agreement between the US Department of Energy, CQ Inc., and ABB Combustion Engineering, Inc. This report covers the period from July 1 through September 30, 1993. Five companies and five host utilities have teamed with CQ Inc. and ABB/CE to perform the work on this project. The work falls under DOE`s Clean Coal Technology Program category of ``Advanced Coal Cleaning.`` The 51-month project will provide the utility industry with a PC expert system to confidently and inexpensively evaluate the potential for coal cleaning, blending, and switching options to reduce emissions while producing lowest cost electricity. Specifically, this project will: (1) Enhance the existing Coal Quality Information System (CQIS) database and Coal Quality Impact Model (CQIM) to allow confident assessment of the effects of cleaning on specific boiler cost and performance; and (2) develop and validate a methodology, Coal Quality Expert (CQE) which allows accurate and detailed predictions of coal quality impacts on total power plant capital cost, operating cost, and performance based upon inputs from inactive bench-scale tests.

  7. Rawlins UCG Demonstration Project. Final technical progress report, May 10, 1988--August 9, 1988

    SciTech Connect

    Not Available

    1988-11-30

    The US Department of Energy and Energy International, Inc. have entered into a Cooperative Agreement to conduct a cost-shared field test demonstrating the operation of commercial-scale steeply dipping bed underground coal gasification (UCG) modules to provide the synthesis gas for a small-scale commercial ammonia plant. The field test and the commercial ammonia plant will be located near Rawlins, Wyoming. During this demonstration test, two or more modules will be operated simultaneously until one module is completely consumed and an additional module is brought on line. During this period, the average coal gasification rate will be between 500 and 1,200 tons per day. A portion of the raw UCC product gas. The UCG facility will continue to operate subsequent. to the demonstration to provide feedstock for the commercial plant. Energy International is responsible for accomplishing specific objectives in accordance with the Statement of Work by designing, installing, operating and monitoring the performance of the UCG modules as the feedstock source for the small-scale commercial ammonia plant. During this period, the project activities focused on project structuring, financing, and project management activities. Because the negotiations with investors were not completed on the schedule anticipated, adjustment of the schedule and activities was necessary. All major activities requiring the expenditure of funds were halted and work was suspended pending the availability of funds and new schedules. These changes have dictated the level of progress or delays for all of the tasks of the project throughout the period of this report.

  8. Theoretical studies in nuclear structure. Final progress report, June 1, 1991--July 31, 1996

    SciTech Connect

    Marshalek, E.R.

    1997-06-01

    The general purview of the project is the theory of collective motion in atomic nuclei. The chief aim is to elucidate the phenomena of (1) anharmonic multiphonon excitations, and (2) collective tilted rotation, both of which are topics of considerable current interest. In the primary stage of an investigation it is often necessary to develop appropriate mathematical tools, as was the case here. In the next stage, the formalism must be tested on simple soluble models. The work described here is mainly concerned with these two stages. The final stage of realistic applications will require more time, manpower and, of course, the necessary funding. Some planning for this last stage has been carried out and anticipated problems axe briefly discussed. As it turns out, both of the above topics can be approached within the unified framework of a theorem that I developed, called the Cranking Bifurcation Theorem (CBT) to be described below. The CBT can be regarded as an outgrowth of the boson expansion method, which provides a general, and, in principal, exact formalism for treating collective excitations. We begin with a brief discussion of the CBT and then continue on to the applications.

  9. Novel catalysts for methane activation. Final progress report, September 30, 1992--April 30, 1996

    SciTech Connect

    Hirschon, A.S.; Du, Y.; Wu, H.J.; Malhotra, R.; Wilson, R.B.

    1996-06-11

    This final report summarizes the results of our research under Contract No. DE-AC22-92PC92112, Novel Catalysts for Methane Activation. In this research we prepared and tested fullerene soots for converting methane into higher hydrocarbons. We conducted the methane conversions using dehydrocoupling conditions, primarily in the temperature regimes of 600{degrees}-1000{degrees}C and atmospheric pressures. The research was divided into three sections. The first section focused on comparing fullerene soots with other forms of carbon such as acetylene black and Norit-A. We found that the fullerene soot was indeed more reactive than the other forms of carbon. However, due to its high reactivity, it was not selective. The second section focused on the effect of metals on the reactivity of the soots, including both transition metals and alkali metals. We found that potassium could enhance the selectivities of fullerene soot to higher hydrocarbons, but the effect was unique to fullerene soot and did not improve the performance of other forms of carbon. The third part focused on the use of co-feeds for methane activation to enhance the selectivities and lower the temperature threshold of methane activation.

  10. Final Progress Report for Award DE-FG07-05ID14637.pdf

    SciTech Connect

    Cathy Dixon

    2012-03-09

    2004-2011 Final Report for AFCI University Fellowship Program. The goal of this effort was to be supportive of university students and university programs - particularly those students and programs that will help to strengthen the development of nuclear-related fields. The program also supported the stability of the nuclear infrastructure and developed research partnerships that are helping to enlarge the national nuclear science technology base. In this fellowship program, the U.S. Department of Energy sought master's degree students in nuclear, mechanical, or chemical engineering, engineering/applied physics, physics, chemistry, radiochemistry, or fields of science and engineering applicable to the AFCI/Gen IV/GNEP missions in order to meet future U.S. nuclear program needs. The fellowship program identified candidates and selected full time students of high-caliber who were taking nuclear courses as part of their degree programs. The DOE Academic Program Managers encouraged fellows to pursue summer internships at national laboratories and supported the students with appropriate information so that both the fellows and the nation's nuclear energy objectives were successful.

  11. Final Progress Report: Isotope Identification Algorithm for Rapid and Accurate Determination of Radioisotopes Feasibility Study

    SciTech Connect

    Rawool-Sullivan, Mohini; Bounds, John Alan; Brumby, Steven P.; Prasad, Lakshman; Sullivan, John P.

    2012-04-30

    This is the final report of the project titled, 'Isotope Identification Algorithm for Rapid and Accurate Determination of Radioisotopes,' PMIS project number LA10-HUMANID-PD03. The goal of the work was to demonstrate principles of emulating a human analysis approach towards the data collected using radiation isotope identification devices (RIIDs). It summarizes work performed over the FY10 time period. The goal of the work was to demonstrate principles of emulating a human analysis approach towards the data collected using radiation isotope identification devices (RIIDs). Human analysts begin analyzing a spectrum based on features in the spectrum - lines and shapes that are present in a given spectrum. The proposed work was to carry out a feasibility study that will pick out all gamma ray peaks and other features such as Compton edges, bremsstrahlung, presence/absence of shielding and presence of neutrons and escape peaks. Ultimately success of this feasibility study will allow us to collectively explain identified features and form a realistic scenario that produced a given spectrum in the future. We wanted to develop and demonstrate machine learning algorithms that will qualitatively enhance the automated identification capabilities of portable radiological sensors that are currently being used in the field.

  12. Role of carbohydrate response element-binding protein (ChREBP) in generating an aerobic metabolic phenotype and in breast cancer progression

    PubMed Central

    Airley, R E; McHugh, P; Evans, A R; Harris, B; Winchester, L; Buffa, F M; Al-Tameemi, W; Leek, R; Harris, A L

    2014-01-01

    Background: The lipogenic transcription factor carbohydrate response element-binding protein (ChREBP) may play a key role in malignant progression of breast cancer by allowing metabolic adaptations to take place in response to changes in oxygenation. Methods: Immunohistochemical analysis of ChREBP was carried out in human breast tumour tissue microarrays representative of malignant progression from normal breast through to metastatic cancer. The ChREBP protein and mRNA expressions were then analysed in a series of breast cancers for correlative analysis with common and breast-specific hypoxia signatures, and survival. Results: In invasive ductal carcinoma, ChREBP correlated significantly with mean ‘downregulated' hypoxia scores (r=0.3, P<0.015, n=67) and in two distinct breast progression arrays, ChREBP protein also increased with malignant progression (P<0.001). However, bioinformatic analysis of a large data set (2136 cases) revealed an apparent reversal in the relationship between ChREBP mRNA level and clinical outcome – not only being significantly correlated with increased survival (log rank P<0.001), but also downregulated in malignant tissue compared with adjacent normal tissue. Conclusion: The ChREBP expression may be reflective of an aerobic metabolic phenotype that may conflict with hypoxia-induced signalling but provide a mechanism for growth at the oxygenated edge of the tumours. PMID:24366300

  13. Coal plasticity at high heating rates and temperatures. Final technical progress report

    SciTech Connect

    Gerjarusak, S.; Peters, W.A.; Howard, J.B.

    1995-05-01

    Plastic coals are important feedstocks in coke manufacture, coal liquefaction, gasification, and combustion. During these processes, the thermoplastic behavior of these coals is also important since it may contribute to desirable or undesirable characteristics. For example, during liquefaction, the plastic behavior is desired since it leads to liquid-liquid reactions which are faster than solid-liquid reactions. During gasification, the elastic behavior is undesired since it leads to caking and agglomeration of coal particles which result in bed bogging in fixed or fluidized bed gasifiers. The plastic behavior of different coals was studied using a fast-response plastometer. A modified plastometer was used to measure the torque required to turn at constant angular speed a cone-shaped disk embedded in a thin layer of coal. The coal particles were packed between two metal plates which are heated electrically. Heating rates, final temperatures, pressures, and durations of experiment ranged from 200--800 K/s, 700--1300 K, vacuum-50 atm helium, and 0--40 s, respectively. The apparent viscosity of the molten coal was calculated from the measured torque using the governing equation of the cone-and-plate viscometer. Using a concentrated suspension model, the molten coal`s apparent viscosity was related to the quantity of the liquid metaplast present during pyrolysis. Seven coals from Argonne National Laboratory Premium Coal Sample Bank were studied. Five bituminous coals, from high-volatile to low-volatile bituminous, were found to have very good plastic behavior. Coal type strongly affects the magnitude and duration of plasticity. Hvb coals were most plastic. Mvb and lvb coals, though the maximum plasticity and plastic period were less. Low rank coals such as subbituminous and lignite did not exhibit any plasticity in the present studies. Coal plasticity is moderately well correlated with simple indices of coal type such as the elemental C,O, and H contents.

  14. Development of a Coal Quality Expert. Final technical progress report No. 8

    SciTech Connect

    Not Available

    1992-06-16

    During the past quarter, Tasks 2, 3, 4, 5, and 6 were active. Data reduction continued for the characterization of raw coal samples collected from five mines located in the Powder Basin in support of the Northern States Power (NSP) King test site. Four flowsheet tests were performed at the CQDC with the Pratt and Utley coals as part of the coal cleanability characterizations being performed for the Alabama Power Company`s (APC) Gaston test site. Babcock and Wilcox (B&W) performed pilot-scale combustion testing of the baseline and alternate coals used for the full-scale test bums at Northern States Power`s King Station. PSI Technology Company (PSIT) and the University of North Dakota`s Energy and Environmental Research Center (EERC) continued to work under ABB/CE to develop the slogging and fouling models. Work continued on the preparation of final test reports for the field tests performed at Public Service Oklahoma`s Northeastern Unit 4 and Mississippi Power Company`s Watson Unit 4, and plans and test schedules were developed for tests to be conducted later this year at Alabama Power Company`s Gaston Unit 5 and Duquesne Light Company`s Cheswick Unit 1. Task 5 and 6 activities were directed at overall CQE program definition, development of the CQE software specification, completion of the Acid Rain Advisor (ARA), and continued formulation of CQE algorithms and submodels. All laboratory analyses required for the raw-coal characterizations of the Powder River Basin coals--collected in support of the NSP King test program--were completed. Coal cleanability tests were performed with the Pratt and Utley Seam coals obtained from the Pittsburg and Midway Coal Company in support of the baseline coal test performed at APC`S Gaston Unit 5.

  15. The Cryogenic AntiCoincidence detector for ATHENA: the progress towards the final pixel design

    NASA Astrophysics Data System (ADS)

    Macculi, Claudio; Piro, Luigi; Cea, Donatella; Colasanti, Luca; Lotti, Simone; Natalucci, Lorenzo; Gatti, Flavio; Bagliani, Daniela; Biasotti, Michele; Corsini, Dario; Pizzigoni, Giulio; Torrioli, Guido; Barbera, Marco; Mineo, Teresa; Perinati, Emanuele

    2014-07-01

    related to one of the last sample produced (namely AC-S5), and steps to reach the final detector design will be discussed.

  16. Final Progress Report for the NASA Inductrack Model Rocket Launcher at the Lawrence Livermore National Laboratory

    SciTech Connect

    Tung, L S; Post, R F; Martinez-Frias, J

    2001-06-27

    The Inductrack magnetic levitation system, developed at the Lawrence Livermore National Laboratory, was studied for its possible use for launching rockets. Under NASA sponsorship, a small model system was constructed at the Laboratory to pursue key technical aspects of this proposed application. The Inductrack is a passive magnetic levitation system employing special arrays of high-field permanent magnets (Halbach arrays) on the levitating cradle, moving above a ''track'' consisting of a close-packed array of shorted coils with which are interleaved with special drive coils. Halbach arrays produce a strong spatially periodic magnetic field on the front surface of the arrays, while canceling the field on their back surface. Relative motion between the Halbach arrays and the track coils induces currents in those coils. These currents levitate the cradle by interacting with the horizontal component of the magnetic field. Pulsed currents in the drive coils, synchronized with the motion of the carrier, interact with the vertical component of the magnetic field to provide acceleration forces. Motional stability, including resistance to both vertical and lateral aerodynamic forces, is provided by having Halbach arrays that interact with both the upper and the lower sides of the track coils. At present, a 7.8 meter track composed of drive and levitation coils has been built and the electronic drive circuitry performs as designed. A 9 kg cradle that carries the Halbach array of permanent magnets has been built. A mechanical launcher is nearly complete which will provide an initial cradle velocity of 9 m/s into the electronic drive section. We have found that the drag forces from the levitation coils were higher than in our original design. However, measurements of drag force at velocities less than 1 m/s are exactly as predicted by theory. Provided here are recommended design changes to improve the track's performance so that a final velocity of 40 m/s can be achieved with

  17. Final Technical Progress Report Long term risk from actinides in the environment: Modes of mobility

    SciTech Connect

    Thomas B. Kirchner

    2002-03-22

    in diameter and approximately 22 cm long. A thin ''marker layer'' of white soil was added to the top of each column followed by a thin layer of soil that had been spiked with 137Cs, cerium and lanthanum was applied to the surface. Approximately 900 cm of water (the equivalent of about 30 years of rainfall) was then applied at a rate of 3.2 L d-1. All of the activity contained in the soil core appeared to be in the top few mm of soil, i.e. there was virtually no movement of the 134Cs labeled particles. Finally, a library of object-oriented model components was created using Visual Basic to support the construction of contaminant transport models. These components greatly simplify the task of building 1- to 3- dimensional simulation models for risk assessment. The model components created under this funding were subsequently applied to help answer questions regarding risks from irrigation associated with potential releases from the Yucca Mountain waste repository.

  18. Serum metabolomic profiling facilitates the non-invasive identification of metabolic biomarkers associated with the onset and progression of non-small cell lung cancer.

    PubMed

    Puchades-Carrasco, Leonor; Jantus-Lewintre, Eloisa; Pérez-Rambla, Clara; García-García, Francisco; Lucas, Rut; Calabuig, Silvia; Blasco, Ana; Dopazo, Joaquín; Camps, Carlos; Pineda-Lucena, Antonio

    2016-03-15

    Lung cancer (LC) is responsible for most cancer deaths. One of the main factors contributing to the lethality of this disease is the fact that a large proportion of patients are diagnosed at advanced stages when a clinical intervention is unlikely to succeed. In this study, we evaluated the potential of metabolomics by 1H-NMR to facilitate the identification of accurate and reliable biomarkers to support the early diagnosis and prognosis of non-small cell lung cancer (NSCLC).We found that the metabolic profile of NSCLC patients, compared with healthy individuals, is characterized by statistically significant changes in the concentration of 18 metabolites representing different amino acids, organic acids and alcohols, as well as different lipids and molecules involved in lipid metabolism. Furthermore, the analysis of the differences between the metabolic profiles of NSCLC patients at different stages of the disease revealed the existence of 17 metabolites involved in metabolic changes associated with disease progression.Our results underscore the potential of metabolomics profiling to uncover pathophysiological mechanisms that could be useful to objectively discriminate NSCLC patients from healthy individuals, as well as between different stages of the disease. PMID:26883203

  19. Serum metabolomic profiling facilitates the non-invasive identification of metabolic biomarkers associated with the onset and progression of non-small cell lung cancer

    PubMed Central

    Puchades-Carrasco, Leonor; Jantus-Lewintre, Eloisa; Pérez-Rambla, Clara; García-García, Francisco; Lucas, Rut; Calabuig, Silvia; Blasco, Ana; Dopazo, Joaquín; Camps, Carlos; Pineda-Lucena, Antonio

    2016-01-01

    Lung cancer (LC) is responsible for most cancer deaths. One of the main factors contributing to the lethality of this disease is the fact that a large proportion of patients are diagnosed at advanced stages when a clinical intervention is unlikely to succeed. In this study, we evaluated the potential of metabolomics by 1H-NMR to facilitate the identification of accurate and reliable biomarkers to support the early diagnosis and prognosis of non-small cell lung cancer (NSCLC). We found that the metabolic profile of NSCLC patients, compared with healthy individuals, is characterized by statistically significant changes in the concentration of 18 metabolites representing different amino acids, organic acids and alcohols, as well as different lipids and molecules involved in lipid metabolism. Furthermore, the analysis of the differences between the metabolic profiles of NSCLC patients at different stages of the disease revealed the existence of 17 metabolites involved in metabolic changes associated with disease progression. Our results underscore the potential of metabolomics profiling to uncover pathophysiological mechanisms that could be useful to objectively discriminate NSCLC patients from healthy individuals, as well as between different stages of the disease. PMID:26883203

  20. Effect on SO/sub 2/ light modulation of plant metabolism. Final progress report, June 1, 1983-May 31, 1985

    SciTech Connect

    Anderson, L.E.

    1985-01-01

    The effect of sulfite and arsenite on light activation in two pisum cultivars was examined. The experiments indicate that the difference in sensitivity to SO/sub 2/ is directly reflected in sensitivity of a thylakoid bound factor to SO/sub 2/. 2 figs. (DT)

  1. Final Progress Report

    SciTech Connect

    Bernstein, Herbert J

    2012-02-06

    The BIOMOL grant was for 'Local System Support for PDB Biological Unit Search and Display' to augment Rasmol's [Bernstein 2000] [Sayle, Milner-White 1995] existing macromolecular display functions with new capabilities by taking advantage of recent increases in local computing power in order to move functionality that is now scattered among various local and remote systems into one local package. Work included new algorithms for molecular surface display, an extended format for Protein Data Bank Entries, work on issues relating to the integration of multiple diffraction images formats.

  2. Final Technical Progress Report

    SciTech Connect

    J.Y. Hwang; R.C. Greenlund

    2002-12-31

    Michigan Technological University has demonstrated major inroads in establishing the viability of utilizing aluminum smelting by-product waste materials in lightweight concrete product applications. The research identified key elements of producing various forms of lightweight concrete products through utilizing various procedures and mixture components with the by-product materials. A process was developed through pilot plant testing that results in additional aluminum recovery at finer sizes, a clean returnable salt product through spray drying technology, and a low-salt-content oxide product with enough aluminum metal content that it can be used to form lightweight cementitious mixtures. Having three distinct products aids in generating favorable process economics. Revenue projections from aluminum recovery and salt recovery are enough to cover processing costs and create a cost-free oxide product to market for lightweight concrete applications. This supply side commercialization strategy offers aluminum by-product recyclers a potentially no cost product, which has been demonstrated through this project to create desirable and marketable lightweight concrete products of various forms. Environmental benefits to the public are tremendous. At best, all dross and salt cake materials have the potential to be completely recycled and utilized. At worst, disposal sites would see a reduced amount of material: a post processed oxide product with little salt and no hydrogen sulfide or ammonia gas generating capability, which, if isolated from high alkali conditions, would pose no reactivity concerns. The US aluminum industry has historically, along with the steel industry, been a leader in recycling metal. The findings from this project, increased metal recovery, improved salt recycling, and demonstrated end uses for oxide residues, will go a long way in helping the aluminum industry obtain 100% material utilization and zero discharge.

  3. Loss of ovarian function in the VCD mouse-model of menopause leads to insulin resistance and a rapid progression into the metabolic syndrome.

    PubMed

    Romero-Aleshire, Melissa J; Diamond-Stanic, Maggie K; Hasty, Alyssa H; Hoyer, Patricia B; Brooks, Heddwen L

    2009-09-01

    Factors comprising the metabolic syndrome occur with increased incidence in postmenopausal women. To investigate the effects of ovarian failure on the progression of the metabolic syndrome, female B(6)C(3)F(1) mice were treated with 4-vinylcyclohexene diepoxide (VCD) and fed a high-fat (HF) diet for 16 wk. VCD destroys preantral follicles, causing early ovarian failure and is a well-characterized model for the gradual onset of menopause. After 12 wk on a HF diet, VCD-treated mice had developed an impaired glucose tolerance, whereas cycling controls were unaffected [12 wk AUC HF mice 13,455 +/- 643 vs. HF/VCD 17,378 +/- 1140 mg/dl/min, P < 0.05]. After 16 wk on a HF diet, VCD-treated mice had significantly higher fasting insulin levels (HF 5.4 +/- 1.3 vs. HF/VCD 10.1 +/- 1.4 ng/ml, P < 0.05) and were significantly more insulin resistant (HOMA-IR) than cycling controls on a HF diet (HF 56.2 +/- 16.7 vs. HF/VCD 113.1 +/- 19.6 mg/dl x microU/ml, P < 0.05). All mice on a HF diet gained more weight than mice on a standard diet, and weight gain in HF/VCD mice was significantly increased compared with HF cycling controls. Interestingly, even without a HF diet, progression into VCD-induced menopause caused a significant increase in cholesterol and free fatty acids. Furthermore, in mice fed a standard diet (6% fat), insulin resistance developed 4 mo after VCD-induced ovarian failure. Insulin resistance following ovarian failure (menopause) was prevented by estrogen replacement. Studies here demonstrate that ovarian failure (menopause) accelerates progression into the metabolic syndrome and that estrogen replacement prevents the onset of insulin resistance in VCD-treated mice. Thus, the VCD model of menopause provides a physiologically relevant means of studying how sex hormones influence the progression of the metabolic syndrome. PMID:19439618

  4. Lipidomics to analyze the influence of diets with different EPA:DHA ratios in the progression of Metabolic Syndrome using SHROB rats as a model.

    PubMed

    Dasilva, Gabriel; Pazos, Manuel; García-Egido, Eduardo; Pérez-Jiménez, Jara; Torres, Josep Lluis; Giralt, Montserrat; Nogués, María-Rosa; Medina, Isabel

    2016-08-15

    The role of specific proportions of ω-3 EPA and DHA, in the modulation of inflammation and oxidative stress markers associated to the progression of Metabolic Syndrome was investigated. Potential inflammatory eicosanoids and docosanoids were discussed together to biomarkers of CVD, obesity, inflammation and oxidative stress in an animal model of metabolic disorders. Results evidenced a noteworthy health effect of 1:1 and 2:1 EPA:DHA proportions over 1:2 EPA:DHA based diets through a down-regulation in the production of strong pro-inflammatory ω-6 eicosanoids, a decrement of biomarkers of oxidative stress, and a modulation of fatty acid desaturase activities and plasma and membrane PUFAs towards greater anti-inflammatory profiles. Outcomes contribute to the general knowledge on the health benefits of marine lipids and their role on the progress of MetS, inflammation and oxidative stress. Results shed light on controversial protective mechanisms of EPA and DHA to better design dietary interventions aimed at reducing MetS. PMID:27006231

  5. Neuron-Glia Crosstalk in the Autonomic Nervous System and Its Possible Role in the Progression of Metabolic Syndrome: A New Hypothesis

    PubMed Central

    Del Rio, Rodrigo; Quintanilla, Rodrigo A.; Orellana, Juan A.; Retamal, Mauricio A.

    2015-01-01

    Metabolic syndrome (MS) is characterized by the following physiological alterations: increase in abdominal fat, insulin resistance, high concentration of triglycerides, low levels of HDL, high blood pressure, and a generalized inflammatory state. One of the pathophysiological hallmarks of this syndrome is the presence of neurohumoral activation, which involve autonomic imbalance associated to hyperactivation of the sympathetic nervous system. Indeed, enhanced sympathetic drive has been linked to the development of endothelial dysfunction, hypertension, stroke, myocardial infarct, and obstructive sleep apnea. Glial cells, the most abundant cells in the central nervous system, control synaptic transmission, and regulate neuronal function by releasing bioactive molecules called gliotransmitters. Recently, a new family of plasma membrane channels called hemichannels has been described to allow the release of gliotransmitters and modulate neuronal firing rate. Moreover, a growing amount of evidence indicates that uncontrolled hemichannel opening could impair glial cell functions, affecting synaptic transmission and neuronal survival. Given that glial cell functions are disturbed in various metabolic diseases, we hypothesize that progression of MS may relies on hemichannel-dependent impairment of glial-to-neuron communication by a mechanism related to dysfunction of inflammatory response and mitochondrial metabolism of glial cells. In this manuscript, we discuss how glial cells may contribute to the enhanced sympathetic drive observed in MS, and shed light about the possible role of hemichannels in this process. PMID:26648871

  6. Pharmacokinetics, metabolism, and excretion of (14)C-labeled belinostat in patients with recurrent or progressive malignancies.

    PubMed

    Calvo, Emiliano; Reddy, Guru; Boni, Valentina; García-Cañamaque, Lina; Song, Tao; Tjornelund, Jette; Choi, Mi Rim; Allen, Lee F

    2016-04-01

    Background Belinostat, a potent pan-inhibitor of histone deacetylase (HDAC) enzymes, is approved in the United States (US) for relapsed/refractory peripheral T-cell lymphoma. In nonclinical studies, bile and feces were identified as the predominant elimination routes (50-70 %), with renal excretion accounting for ~30-50 %. A Phase 1 human mass balance study was conducted to identify species-dependent variations in belinostat metabolism and elimination. Methods Patients received a single 30-min intravenous (IV) infusion of (14)C-labeled belinostat (1500 mg). Venous blood samples and pooled urine and fecal samples were evaluated using liquid chromatography - tandem mass spectroscopy for belinostat and metabolite concentrations pre-infusion through 7 days post-infusion. Total radioactivity was determined using liquid scintillation counting. Continued treatment with nonradiolabled belinostat (1000 mg/m(2) on Days 1-5 every 21 days) was permitted. Results Belinostat was extensively metabolized and mostly cleared from plasma within 8 h (N = 6), indicating that metabolism is the primary route of elimination. Systemic exposure for the 5 major metabolites was >20 % of parent, with belinostat glucuronide the predominant metabolite. Mean recovery of radioactive belinostat was 94.5 % ± 4.0 %, with the majority excreted within 48 and 96 h in urine and feces, respectively. Renal elimination was the principal excretion route (mean 84.8 % ± 9.8 % of total dose); fecal excretion accounted for 9.7 % ± 6.5 %. Belinostat was well tolerated, with mostly mild to moderate adverse events and no treatment-related severe/serious events. Conclusion Mass balance was achieved (~95 % mean recovery), with metabolism identified as the primary route of elimination. Radioactivity was predominantly excreted renally as belinostat metabolites. PMID:26769244

  7. Photons, Photosynthesis, and High-Performance Computing: Challenges, Progress, and Promise of Modeling Metabolism in Green Algae

    SciTech Connect

    Chang, C. H.; Graf, P.; Alber, D. M.; Kim, K.; Murray, G.; Posewitz, M.; Seibert, M.

    2008-01-01

    The complexity associated with biological metabolism considered at a kinetic level presents a challenge to quantitative modeling. In particular, the relatively sparse knowledge of parameters for enzymes with known kinetic responses is problematic. The possible space of these parameters is of high-dimension, and sampling of such a space typifies a combinatorial explosion of possible dynamic states. However, with sufficient quantitative transcriptomics, proteomics, and metabolomics data at hand, these challenges could be met by high-performance software with sampling, fitting, and optimization capabilities. With this in mind, we present the High-Performance Systems Biology Toolkit HiPer SBTK, an evolving software package to simulate, fit, and optimize metabolite concentrations and fluxes within the space of rate and binding parameters associated with detailed enzyme kinetic models. We present our chosen modeling paradigm for the formulation of metabolic pathway models, the means to address the challenge of representing such models in a precise and persistent fashion using the standardized Systems Biology Markup Language, and our second-generation model of H2-associated Chlamydomonas metabolism. Processing of such models for hierarchically parallelized simulation and optimization, job specification by the user through a GUI interface, software capabilities and initial scaling data, and the mapping of the computation to biological questions is also discussed. Moreover, we present near-term future software and model development goals.

  8. Metabolic products, mass spectral analyses, and synthesis of toxic trichothecenes. Final report, 15 April 1982-14 July 1985

    SciTech Connect

    Mirocha, C.J.

    1985-07-31

    A mass spectral library of the trichothecenes was developed and delivered to USAMRIID. The structure of Fusarochromanone (causes bone deformation) was elucidated and the biological activity of this metabolite was determined. Metabolic studies of T-2 toxin were determined in chickens and the metabolites were identified. Similarly, a kinetic study of T-2 metabolism was done using a cow as the subject. De-epoxy-diacetoxyscirpenol was found in a Fusarium culture for the first time and de-epoxy-T2 tetraol was found in cow urine for the first time. Morphologic lesions of T-2 toxin in the cat were described.

  9. Correlating tumor metabolic progression index measured by serial FDG PET-CT, apparent diffusion coefficient measured by magnetic resonance imaging (MRI) and blood genomics to patient’s outcome in advanced colorectal cancer: the CORIOLAN study

    PubMed Central

    2014-01-01

    Background Metastatic colorectal cancer (mCRC) may present various behaviours that define different courses of tumor evolution. There is presently no available tool designed to assess tumor aggressiveness, despite the fact that this is considered to have a major impact on patient outcome. Methods/Design CORIOLAN is a single-arm prospective interventional non-therapeutic study aiming mainly to assess the natural tumor metabolic progression index (TMPI) measured by serial FDG PET-CT without any intercurrent antitumor therapy as a prognostic factor for overall survival (OS) in patients with mCRC. Secondary objectives of the study aim to test the TMPI as a prognostic marker for progression-free survival (PFS), to assess the prognostic value of baseline tumor FDG uptake on PFS and OS, to compare TMPI to classical clinico-biological assessment of prognosis, and to test the prognostic value on OS and PFS of MRI-based apparent diffusion coefficient (ADC) and variation of vADC using voxel-based diffusion maps. Additionally, this study intends to identify genomic and epigenetic factors that correlate with progression of tumors and the OS of patients with mCRC. Consequently, this analysis will provide information about the signaling pathways that determine the natural and therapy-free course of the disease. Finally, it would be of great interest to investigate whether in a population of patients with mCRC, for which at present no known effective therapy is available, tumor aggressiveness is related to elevated levels of circulating tumor cells (CTCs) and to patient outcome. Discussion Tumor aggressiveness is one of the major determinants of patient outcome in advanced disease. Despite its importance, supported by findings reported in the literature of extreme outcomes for patients with mCRC treated with chemotherapy, no objective tool allows clinicians to base treatment decisions on this factor. The CORIOLAN study will characterize TMPI using FDG-PET-based metabolic imaging

  10. Summer investigations into the metabolic diversity of the microbial world. Progress report, May 5, 1992--April 30, 1993

    SciTech Connect

    Breznak, J.; Dworkin, M.

    1993-05-17

    The philosophy of the course described here is to underscore the essence of microbiology which is diversity>: diversity of morphology and cellular development, behavior, and metabolic and physiological functions. Emphasis is on microbes other than those customarily covered in conventional microbiology courses and includes: the archaebacteria, extremophiles, and array of obligate anaerobes, various phototrophs, and those microbes exhibiting complex developmental cycles. Also included are microbes carrying out a variety of transformations of organic and inorganic compounds, as well as those which normally occur in symbiotic association with other microbes or with higher forms of life.

  11. Primate polonium metabolic models and their use in estimation of systemic radiation doses from bioassay data. Final report

    SciTech Connect

    Cohen, N.

    1989-03-15

    A Polonium metabolic model was derived and incorporated into a Fortran algorithm which estimates the systemic radiation dose from {sup 210}Po when applied to occupational urine bioassay data. The significance of the doses estimated are examined by defining the degree of uncertainty attached to them through comprehensive statistical testing procedures. Many parameters necessary for dosimetry calculations (such as organ partition coefficients and excretion fractions), were evaluated from metabolic studies of {sup 210}Po in non-human primates. Two tamarins and six baboons were injected intravenously with {sup 210}Po citrate. Excreta and blood samples were collected. Five of the baboons were sacrificed at times ranging from 1 day to 3 months post exposure. Complete necropsies were performed and all excreta and the majority of all skeletal and tissue samples were analyzed radiochemically for their {sup 210}Po content. The {sup 210}Po excretion rate in the baboon was more rapid than in the tamarin. The biological half-time of {sup 210}Po excretion in the baboon was approximately 15 days while in the tamarin, the {sup 210}Po excretion rate was in close agreement with the 50 day biological half-time predicted by ICRP 30. Excretion fractions of {sup 210}Po in the non-human primates were found to be markedly different from data reported elsewhere in other species, including man. A thorough review of the Po urinalysis procedure showed that significant recovery losses resulted when metabolized {sup 210}Po was deposited out of raw urine. Polonium-210 was found throughout the soft tissues of the baboon but not with the partition coefficients for liver, kidneys, and spleen that are predicted by the ICRP 30 metabolic model. A fractional distribution of 0.29 for liver, 0.07 for kidneys, and 0.006 for spleen was determined. Retention times for {sup 210}Po in tissues are described by single exponential functions with biological half-times ranging from 15 to 50 days.

  12. Impact of Gentamicin Coadministration along with High Fructose Feeding on Progression of Renal Failure and Metabolic Syndrome in Sprague-Dawley Rats

    PubMed Central

    Ibraheem, Zaid O.; Basir, Rusliza; Aljobory, Ahmad Kh.; Ibrahim, Omar E.; Alsumaidaee, Ajwad; Yam, Mun Fee

    2014-01-01

    The current study evaluates the impact of high fructose feeding in rat model of gentamicin induced nephrotoxicity. Sprague-Dawley rats weighing 180–200 g were randomized into four groups; (C) received standard rodents chow with free access to ad libitum drinking water for 8 weeks and was considered as control, (F) received standard rodents chow with free access to drinking water supplemented with 20% (W/V) fructose for the same abovementioned period, (FG) was fed as group F and was given 80 mg/kg (body weight)/day gentamicin sulphate intraperitoneally during the last 20 days of the feeding period, and (G) was given gentamicin as above and fed as group C. Renal function was assessed at the end of the treatment period through measuring serum creatinine, uric acid and albumin, creatinine clearance, absolute and fractional excretion of both sodium and potassium, twenty-four-hour urinary excretion of albumin, and renal histology. For metabolic syndrome assessment, fasting plasma glucose and insulin were measured and oral glucose tolerance test was performed throughout the treatment period. Results showed that gentamicin enhances progression of fructose induced metabolic syndrome. On the other hand, fructose pretreatment before gentamicin injection produced a comparable degree of renal dysfunction to those which were given fructose-free water but the picture of nephrotoxicity was somewhat altered as it was characterized by higher extent of glomerular congestion and protein urea. Overall, more vigilance is required when nephrotoxic drugs are prescribed for patients with fructose induced metabolic syndrome. PMID:25045706

  13. (Summer investigations into the isolation, cultivation and metabolism of anaerobes involved in biodegradation): Progress report, year 4, summer 1988

    SciTech Connect

    Not Available

    1988-01-01

    In the laboratory our students were trained in modern techniques for the isolation and study of a wide variety of microbes from marine and brackish environments. Special emphasis was placed on anaerobes and archaebacteria. Microbial groups that were studied included the propionic bacteria, clostridia, methanogens, acetogens, hydrogen oxidizing anaerobes and aerobes, sulfate-reducing bacteria and sulfur-reducing bacteria, anoxic photosynthetic bacteria, cyanobacteria, spirochetes, symbiotic and non-symbiotic nitrogen fixing bacteria, luminescent bacteria, iron bacteria, magnetic bacteria, and sulfur oxidizing bacteria. The permanent staff led discussions and presented lectures on the metabolism, physiology and biochemistry of the groups listed above. Material was also presented on motility and chemotaxis of bacteria, and particular emphasis was given to molecular approaches to studying evolution of bacteria. We also had five successful Microbiology Mini-symposia (see attached schedule). These one-day symposia involved lecture/seminar presentations by investigators involved in state-of-the-art working particularly exciting areas within the scope of our course.

  14. 40 CFR 60.1585 - What are my requirements for meeting increments of progress and achieving final compliance?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... SOURCES Emission Guidelines and Compliance Times for Small Municipal Waste Combustion Units Constructed on... construction. (4) Complete onsite construction. (5) Achieve final compliance. (b) Class II units. If you...

  15. Reading Achievement in Disadvantaged Children as a Consequence of Non Verbal Perceptual Training. Final Technical Progress Report.

    ERIC Educational Resources Information Center

    Elkind, David; Deblinger, Jo Ann

    The theoretical orientation based on perceptual development, proposed by Piaget in 1961, is the starting point of this investigation. According to Piaget, the perception of the young child is "centered" on dominant aspects of the field. With maturity, perception becomes "decentered" and progressively freed from the field. The visual training…

  16. Main research accomplishments since the grant was last reviewed competitively. [Final technical progress report, November 1, 1992--July 31, 1993

    SciTech Connect

    Prakash, L.

    1993-11-01

    This project deals with the characterization of DNA repair genes and their encoded proteins involved in the incision step of excision repair and in postreplication repair and mutagenesis following exposure to UV light in eukaryotes: the yeast Saccharomyces cerevisiae and humans. Summarized in this report is progress in achieving the goals of this project.

  17. The effect of variable calcium and very low calcium diets on human calcium metabolism. Ph.D. Thesis. Final Report

    NASA Technical Reports Server (NTRS)

    Chu, J.

    1971-01-01

    The effects of a very low calcium diet, with variable high and low protein intake, on the dynamics of calcium metabolism and the mechanism of calciuretics, are examined. The experiment, using male subjects, was designed to study the role of intestinal calcium absorption on urinary calcium excretion, and the rate of production of endogeneously secreted calcium in the gastrointestinal tract. The study showed an average of 70% fractional absorption rate during very low calcium intake, and that a decrease in renal tubular reabsorption of calcium is responsible for calciuretic effects of high protein intake. The study also indicates that there is a tendency to develop osteoporosis after long periods of low calcium intake, especially with a concurrent high protein intake.

  18. Final Technical Progress Report; Closeout Certifications; CSSV Newsletter Volume I; CSSV Newsletter Volume II; CSSV Activity Journal; CSSV Final Financial Report

    SciTech Connect

    Houston, Johnny L; Geter, Kerry

    2013-08-23

    This Project?s third year of implementation in 2007-2008, the final year, as designated by Elizabeth City State University (ECSU), in cooperation with the National Association of Mathematicians (NAM) Inc., in an effort to promote research and research training programs in computational science ? scientific visualization (CSSV). A major goal of the Project was to attract the energetic and productive faculty, graduate and upper division undergraduate students of diverse ethnicities to a program that investigates science and computational science issues of long-term interest to the Department of Energy (DoE) and the nation. The breadth and depth of computational science?scientific visualization and the magnitude of resources available are enormous for permitting a variety of research activities. ECSU?s Computational Science-Science Visualization Center will serve as a conduit for directing users to these enormous resources.

  19. Long-term omega-3 fatty acid supplementation prevents expression changes in cochlear homocysteine metabolism and ameliorates progressive hearing loss in C57BL/6J mice.

    PubMed

    Martínez-Vega, Raquel; Partearroyo, Teresa; Vallecillo, Néstor; Varela-Moreiras, Gregorio; Pajares, María A; Varela-Nieto, Isabel

    2015-12-01

    Omega-3 polyunsaturated fatty acids (PUFAs) are essential nutrients well known for their beneficial effects, among others on cognitive development and maintenance, inflammation and oxidative stress. Previous studies have shown an inverse association between high plasma levels of PUFAs and age-related hearing loss, and the relationship between low serum folate and elevated plasma homocysteine levels and hearing loss. Therefore, we used C57BL/6J mice and long-term omega-3 supplementation to evaluate the impact on hearing by analyzing their auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) thresholds. The omega-3 group showed significantly lower ABR hearing thresholds (~25 dB sound pressure level) and higher DPOAE amplitudes in mid-high frequencies when compared to the control group. These changes did not correlate with alterations between groups in plasma homocysteine or serum folate levels as measured by high-performance liquid chromatography and a microbiological method, respectively. Aging in the control group was associated with imbalanced cytokine expression toward increased proinflammatory cytokines as determined by quantitative reverse transcriptase polymerase chain reaction; these changes were prevented by omega-3 supplementation. Genes involved in homocysteine metabolism showed decreased expression during aging of control animals, and only alterations in Bhmt and Cbs were significantly prevented by omega-3 feeding. Western blotting showed that omega-3 supplementation precluded the CBS protein increase detected in 10-month-old controls but also produced an increase in BHMT protein levels. Altogether, the results obtained suggest a long-term protective role of omega-3 supplementation on cochlear metabolism and progression of hearing loss. PMID:26321228

  20. Development of laser excited atomic fluorescence and ionization methods. Final technical progress report, May 1, 1988--December 31, 1991

    SciTech Connect

    Winefordner, J.D.

    1991-12-31

    Progress report: May 1, 1988 to December 31, 1991. The research supported by DE-FG05-88ER13881 during the past (nearly) 3 years can be divided into the following four categories: (1) theoretical considerations of the ultimate detection powers of laser fluorescence and laser ionization methods; (2) experimental evaluation of laser excited atomic fluorescence; (3) fundamental studies of atomic and molecular parameters in flames and plasmas; (4) other studies.

  1. Final Technical Progress Report: High-Efficiency Low-Cost Thin-Film GaAs Photovoltaic Module Development Program; July 14, 2010 - January 13, 2012

    SciTech Connect

    Mattos, L.

    2012-03-01

    This is the final technical progress report of the High-Efficiency Low-Cost Thin-Film GaAs Photovoltaic Module Development Program. Alta Devices has successfully completed all milestones and deliverables established as part of the NREL PV incubator program. During the 18 months of this program, Alta has proven all key processes required to commercialize its solar module product. The incubator focus was on back end process steps directed at conversion of Alta's high quality solar film into high efficiency 1-sun PV modules. This report describes all program deliverables and the work behind each accomplishment.

  2. Effect of petroleum-related pollutants on Aurelia growth and development. Final progress report, September 12, 1977-August 31, 1982

    SciTech Connect

    Spangenberg, D.B.

    1982-01-01

    Petroleum-related hydrocarbons were tested using the Aurelia Metamorphosis Test System. In addition, extensive studies were made of the effects of Alaskan crude petroleum oil, cadmium, and sodium azide on Aurelia metamorphosis. The Aurelia Budding Test System was applied to phenol, aniline, and naphthalene and the Aurelia Genetic Modification Test System was developed to determine whether chemically-treated organisms had genetic damage which could be revealed in progeny over a long period of time. The Aurelia Genetic Modification Test System was applied to aniline, phenol, Alaskan crude petroleum oil, and sodium azide-treated organisms. It is concluded that the Aurelia can be used effectively to ferret out subtle effects of marine pollutants as well as far-reaching effects passed on through progeny over a long period of time. Pollutant effects are most rapidly revealed, however, in organisms undergoing metamorphosis especially with regard to effects related to iodine metabolism, calcium metabolism, and behavioral and morphological teratology. The premise is that specific effects of environmental pollutants must be known in order that these effects may be neutralized or prevented. Through an understanding of mechanisms of action of various pollutant components in simple indicator organisms such as Aurelia, it may ultimately be possible to maintain high standards of energy production and to have a safe and productive marine environment at the same time.

  3. Sucrose metabolism: gateway to diverse carbon use and sugar signaling.

    PubMed

    Ruan, Yong-Ling

    2014-01-01

    Sucrose metabolism plays pivotal roles in development, stress response, and yield formation, mainly by generating a range of sugars as metabolites to fuel growth and synthesize essential compounds (including protein, cellulose, and starch) and as signals to regulate expression of microRNAs, transcription factors, and other genes and for crosstalk with hormonal, oxidative, and defense signaling. This review aims to capture the most exciting developments in this area by evaluating (a) the roles of key sucrose metabolic enzymes in development, abiotic stress responses, and plant-microbe interactions; (b) the coupling between sucrose metabolism and sugar signaling from extra- to intracellular spaces; (c) the different mechanisms by which sucrose metabolic enzymes could perform their signaling roles; and (d) progress on engineering sugar metabolism and transport for high yield and disease resistance. Finally, the review outlines future directions for research on sugar metabolism and signaling to better understand and improve plant performance. PMID:24579990

  4. Fusion reactor systems studies. Progress report for the period November 1, 1996--October 31, 1997, and final report

    SciTech Connect

    El-Guebaly, L.A.; Blanchard, J.P.; Kulcinski, G.L.

    1997-08-01

    During FY97, the University of Wisconsin Fusion Technology Institute personnel have participated in the ARIES-RS and the ARIES-ST projects. The main areas of effort are: (1) neutronics analysis; (2) shielding of components and personnel; (3) neutron wall loading distribution; (4) radiation damage to in-vessel components; (5) components lifetimes; (6) embrittled materials designs issues; (7) stress and structural analysis; (8) activation, LOCA, and safety analysis; (9) support and fabrication of components; (10) vacuum system; and (11) maintenance. Progress made in these areas are summarized.

  5. Development of a Coal Quality Expert. Final technical progress report No. 12, [January 1--March 31, 1993

    SciTech Connect

    Not Available

    1993-08-12

    During the past quarter, Tasks 3, 4, 5, and 6 were active. Task 3 Pilot Scale Combustion Testing activity included data analysis of pilot- and bench-scale combustion samples in support of the development of CQE slogging and fouling models. Under Task 4, field testing at the fifth host utility site -- New England Power Service Company`s Brayton Point Unit 3 -- was completed in March with the testing of the alternate coal. Test plans were finalized for the sixth and final field test to be performed at Brayton Point Unit 2 in April 1993. Tasks 5 and 6 activities were directed at design and development of CQE base classes and objects, continued formulation and integration of CQE algorithms and submodels, development of the user interface prototype, and preparation of the Fireside Advisor.

  6. Filling Knowledge Gaps in Biological Networks: integrating global approaches to understand H2 metabolism in Chlamydomonas reinhardtii - Final Report

    SciTech Connect

    Posewitz, Matthew C

    2011-06-30

    The green alga Chlamydomonas reinhardtii (Chlamydomonas) has numerous genes encoding enzymes that function in fermentative pathways. Among these genes, are the [FeFe]-hydrogenases, pyruvate formate lyase, pyruvate ferredoxin oxidoreductase, acetate kinase, and phosphotransacetylase. We have systematically undertaken a series of targeted mutagenesis approaches to disrupt each of these key genes and omics techniques to characterize alterations in metabolic flux. Funds from DE-FG02-07ER64423 were specifically leveraged to generate mutants with disruptions in the genes encoding the [FeFe]-hydrogenases HYDA1 and HYDA2, pyruvate formate lyase (PFL1), and in bifunctional alcohol/aldehyde alcohol dehydrogenase (ADH1). Additionally funds were used to conduct global transcript profiling experiments of wildtype Chlamydomonas cells, as well as of the hydEF-1 mutant, which is unable to make H2 due to a lesion in the [FeFe]-hydrogenase biosynthetic pathway. In the wildtype cells, formate, acetate and ethanol are the dominant fermentation products with traces of CO2 and H2 also being produced. In the hydEF-1 mutant, succinate production is increased to offset the loss of protons as a terminal electron acceptor. In the pfl-1 mutant, lactate offsets the loss of formate production, and in the adh1-1 mutant glycerol is made instead of ethanol. To further probe the system, we generated a double mutant (pfl1-1 adh1) that is unable to synthesize both formate and ethanol. This strain, like the pfl1 mutants, secreted lactate, but also exhibited a significant increase in the levels of extracellular glycerol, acetate, and intracellular reduced sugars, and a decline in dark, fermentative H2 production. Whereas wild-type Chlamydomonas fermentation primarily produces formate and ethanol, the double mutant performs a complete rerouting of the glycolytic carbon to lactate and glycerol. Lastly, transcriptome data have been analysed for both the wildtype and hydEF-1, that correlate with our

  7. Organization of the R chromosome region in maize: Final progress report, June 1, 1983--May 31, 1986

    SciTech Connect

    Kermicle, J.

    1989-02-01

    For the present study, insertional mutagenesis using transposable sequences proved the most effective means of producing /und R/ variants for fine structure study. Considerable effort was directed toward developing this means of mutagenesis. It was also necessary to describe the pattern of recombination that prevailed in this region when insertions were present. Thus some of the topics considered as separate items in the following discussion concern transposable element behavior and recombination as such. Until recently, genetic analysis had been the principal means of investigating /und R/ structure and function. With the advent of molecular cloning of maize genes by transposon tagging, a more direct means of investigating /und R/ structure was envisioned. This possibility was realized. We are now collaborating with these investigators to integrate genetic and molecular sources of evidence. This document summarizes publications of research sponsored by this grant, and recent findings that appear to be major advances but concerning which further experiments are in progress. 12 refs.

  8. Final Progress Report: FRACTURE AND SUBCRITICAL DEBONDING IN THIN LAYERED STRUCTURES: EXPERIMENTS AND MULTI-SCALE MODELING

    SciTech Connect

    Reinhold H. Dauskardt

    2005-08-30

    Final technical report detailing unique experimental and multi-scale computational modeling capabilities developed to study fracture and subcritical cracking in thin-film structures. Our program to date at Stanford has studied the mechanisms of fracture and fatigue crack-growth in structural ceramics at high temperature, bulk and thin-film glasses in selected moist environments where we demonstrated the presence of a true mechanical fatigue effect in some glass compositions. We also reported on the effects of complex environments and fatigue loading on subcritical cracking that effects the reliability of MEMS and other micro-devices using novel micro-machined silicon specimens and nanomaterial layers.

  9. Randomized controlled trial to evaluate the effects of combined progressive exercise on metabolic syndrome in breast cancer survivors: rationale, design, and methods

    PubMed Central

    2014-01-01

    Background Metabolic syndrome (MetS) is increasingly present in breast cancer survivors, possibly worsened by cancer-related treatments, such as chemotherapy. MetS greatly increases risk of cardiovascular disease and diabetes, co-morbidities that could impair the survivorship experience, and possibly lead to cancer recurrence. Exercise has been shown to positively influence quality of life (QOL), physical function, muscular strength and endurance, reduce fatigue, and improve emotional well-being; however, the impact on MetS components (visceral adiposity, hyperglycemia, low serum high-density lipoprotein cholesterol, hypertriglyceridemia, and hypertension) remains largely unknown. In this trial, we aim to assess the effects of combined (aerobic and resistance) exercise on components of MetS, as well as on physical fitness and QOL, in breast cancer survivors soon after completing cancer-related treatments. Methods/Design This study is a prospective randomized controlled trial (RCT) investigating the effects of a 16-week supervised progressive aerobic and resistance exercise training intervention on MetS in 100 breast cancer survivors. Main inclusion criteria are histologically-confirmed breast cancer stage I-III, completion of chemotherapy and/or radiation within 6 months prior to initiation of the study, sedentary, and free from musculoskeletal disorders. The primary endpoint is MetS; secondary endpoints include: muscle strength, shoulder function, cardiorespiratory fitness, body composition, bone mineral density, and QOL. Participants randomized to the Exercise group participate in 3 supervised weekly exercise sessions for 16 weeks. Participants randomized to the Control group are offered the same intervention after the 16-week period of observation. Discussion This is the one of few RCTs examining the effects of exercise on MetS in breast cancer survivors. Results will contribute a better understanding of metabolic disease-related effects of resistance and

  10. Regulation and genetic organization of hydrogenase: Final progress report for the period June 1, 1985--July 31, 1988

    SciTech Connect

    Krasna, A.I.

    1988-10-01

    Hydrogenase is an enzyme which plays an important role in the anaerobic metabolism of many bacteria. The objectives of the research were to elucidate the regulation and genetic organization of hydrogenase in microorganisms. A mutation in the E. coli hydE gene leads to loss of all hydrogenase activities and isoenzymes as well as all formate-related activities. A 0.9 kb DNA fragment has been cloned from an E. coli genomic DNA library which restored all hydrogenase and formate activities to a hydE mutant strain. This gene coded for a polypeptide of subunit mw 36 kDa which is required for hydrogenase synthesis. It is involved in incorporation of nickel into hydrogenase. A mutation in the E coli hupB gene leads to the loss of the uptake of H/sub 2/ by dyes and the ability to grow on fumarate plus H/sub 2/, but expresses normal levels of hydrogenase when assayed by deuterium exchange. This mutation also leads to loss of all formate-related activities. The mutation mapped near minute 17 and a single mutation was responsible for loss of both activities. A 1.4 kb DNA fragment was isolated which restored the hydrogen uptake activities and coded for a polypeptide of subunit mw 30 kDa. Dna fragments have been isolated from Chromatium vinosum and Proteus vulgaris which restored hydrogenase activities to E. coli strains with mutations in the hydA or hydB regulatory genes and which lack all hydrogenase activities. 6 refs., 12 figs.

  11. Positron tomographic imaging of tumors using monoclonal antibodies. Final progress report, April 15, 1989--October 31, 1995

    SciTech Connect

    Zalutsky, M.R.

    1997-02-01

    The overall objective of this research is to develop methods for utilizing positron emission tomography (PET) to increase the clinical potential of radiolabeled monoclonal antibodies (MAbs). Enhancement of MAb tumor localization by hyperthermia also was proposed. Studies were to have been performed with both {sup 18}F and {sup 124}I; however, the lack of its availability (until quite recently) prevented experiments with {sup 124}I. Instead, two additional lines of inquiry were initiated in which they utilized aspects of the radiofluorination chemistries originally developed for MAbs for labeling chemotactic peptides and meta-iodobenzylguanidine (MIBG) analogues with {sup 18}F. This final report summarizes the original specific aims and the main research accomplishments in studies of mouse, dog and human models.

  12. Chemical and geochemical studies off the coast of Washington. Final report of progress, July 1983-July 1985

    SciTech Connect

    Carpenter, R.

    1985-07-01

    This report summarizes progress from July 1983 through conclusion in July 1985 of a series of marine chemical and geochemical investigations involving both laboratory studies and field studies off the coast of Washington. Most of our field work the past few years has been on the Washington continental shelf, slope, and the submarine canyons indenting the shelf north of the Columbia River. Our aim has been to provide basic data required to characterize underlying chemical and physical processes and their rates which control the distribution, concentrations, and ultimate fate of some of the potentially hazardous agents associated with fossil fuel and/or nuclear power production or transportation. We concentrated on several processes which we feel are of special importance in the sea, and developed methodologies and expertise to study them. Laboratory and field experiments and theories derived from them were used iteratively to investigate: (1) vertical transfer of trace chemicals from surface seawaters to underlying waters and sediments; (2) processes which may transfer certain chemicals from sediments back into the overlying water column; (3) redox processes which besides changing valence states of certain chemicals may alter their precipitation/dissolution tendencies, their biological availability and/or toxicity; and (4) accumulation histories of potentially hazardous chemicals in sediments during the past 100 years.

  13. Measurement and apportionment of radon source terms for modeling indoor environments. Final progress report, March 1990--August 1992

    SciTech Connect

    Harley, N.H.

    1992-12-31

    During the present 2 1/2 year contract period, we have made significant Progress in modeling the source apportionment of indoor {sup 222}Rn and in {sup 222}Rn decay product dosimetry. Two additional areas were worked on which we believe are useful for the DOE Radon research Program. One involved an analysis of the research house data, grouping the hourly house {sup 222}Rn measurements into 2 day, 7 day and 90 day intervals to simulate the response of passive monitors. Another area requiring some attention resulted in a publication of 3 years of our indoor/outdoor measurements in a high-rise apartment. Little interest has been evinced in apartment measurements yet 20% of the US population lives in multiple-family dwellings, not in contact with the ground. These data together with a summary of all other published data on apartments showed that apartments have only about 50% greater {sup 222}Rn concentration than the measured outdoor {sup 222}Rn. Apartment dwellers generally represent a low risk group regarding {sup 222}Rn exposure. The following sections describe the main projects in some detail.

  14. Parallel logic programming and parallel systems software and hardware. Progress report (Final), 1 April 1988-31 March 1989

    SciTech Connect

    Minker, J.

    1989-07-29

    This progress report summarizes work performed under AFOSR-88-0152 on parallel logic programming, problem solving, and deductive data bases. A parallel problem-solving system, PRISM (Parallel Inference System), that was implemented on McMOB was ported to the BBN Butterfly machine. Two versions of PRISM were developed and are operational on the Butterfly: a message-passing ring-structure system and a shared-memory system. Experimental testing of PRISM on McMOB continued, while experiments were also conducted on the Butterfly systems. Three enhancements were made and completed during the grant period. These are: a capability to handle negated queries and a capability to assert and retract statements. In addition to the above, work continued in the area of informative answers to queries in deductive data bases. A thesis was completed on the subject. An interpreter was developed and is running, that can take restricted natural language as input and can respond with a cooperative natural language output. In the area of parallel software development, the following were accomplished. Theoretical work on slicing/splicing was completed. Tools were provided for software development using artificial-intelligence techniques. AI software for massively parallel architectures was started.

  15. Bioconversion of coal derived synthesis gas to liquid fuels. Final quarterly technical progress report, July 1, 1993--September 30, 1993

    SciTech Connect

    Jain, M.K.; Worden, R.M.; Grethlein, H.

    1993-10-25

    The overall objective of the project is to develop an integrated two stage fermentation process for conversion of coal-derived synthesis gas to a mixture of alcohols. This is achieved in two steps. In the first step, Butyribacterium methylotrophicum converts carbon monoxide (CO) to butyric and acetic acids. Subsequent fermentation of the acids by Clostridium acetobutylicum leads to the production of butanol and ethanol. The tasks for this quarter were: (1) development/isolation of superior strains for fermentation of syngas, (2) optimization of process conditions for fermentation of syngas, (3) evaluation of bioreactor configuration for improved mass transfer of syngas, (4) development of a membrane-based pervaporation system, (5) optimization of process conditions for reducing carbon and electron loss by H{sub 2}-CO{sub 2} fermentation, and (6) synthesis gas fermentation in single-stage by co-culture. Progress is reported in isolation of CO utilizing anaerobic strains; investigating the product profile for the fermentation of syngas by B. methylotrophicum; and determining the effect of carbon monoxide on growth of C. acetobutylicum.

  16. Construction of a genome-wide human BAC-Unigene resource. Final progress report, 1989--1996

    SciTech Connect

    Lim, C.S.; Xu, R.X.; Wang, M.

    1996-12-31

    Currently, over 30,000 mapped STSs and 27,000 mapped Unigenes (non-redundant, unigene sets of cDNA representing EST clusters) are available for human alone. A total of 44,000 Unigene cDNA clones have been supplied by Research Genetics. Unigenes, or cDNAs are excellent resource for map building for two reasons. Firstly, they exist in two alternative forms -- as both sequence information for PCR primer pairs, and cDNA clones -- thus making library screening by colony hybridization as well as pooled library PCR possible. The authors have developed an efficient and robust procedure to screen genomic libraries with large number of DNA probes. Secondly, the linkage and order of expressed sequences, or genes are highly conserved among human, mouse and other mammalian species. Therefore, mapping with cDNA markers rather than random anonymous STSs will greatly facilitate comparative, evolutionary studies as well as physical map building. They have currently deconvoluted over 10,000 Unigene probes against a 4X coverage human BAC clones from the approved library D by high density colony hybridization method. 10,000 batches of Unigenes are arrayed in an imaginary 100 X 100 matrix from which 100 row pools and 100 column pools are obtained. Library filters are hybridized with pooled probes, thus reducing the number of hybridization required for addressing the positives for each Unigene from 10,000 to 200. Details on the experimental scheme as well as daily progress report is posted on the Web site (http://www.tree.caltech.edu).

  17. Highly nucleophilic acetylide, vinyl, and vinylidene complexes. Final progress report, 1 January 1991--31 March 1994

    SciTech Connect

    Geoffroy, G.L.

    1994-10-04

    In the course of this research the authors found that the anionic alkynyl complex [Cp{prime}(CO)(PPh{sub 3})Mn-C{triple_bond}C-CH{sub 3}]{sup {minus}} can be generated in situ by the addition of two equivalents of n-BuLi to a solution of the carbene complex Cp{prime}(CO)(PPh{sub 3})Mn{double_bond}C(OMe)CH{sub 2}CH{sub 3}. It was also found that the highly nucleophilic propynyl complex [Cp(CO)(PPh{sub 3})Mn-C{triple_bond}C-Me]{sup {minus}} reacts with a variety of aldehydes and ketones in the presence of BF{sub 3}{center_dot}Et{sub 2}O to give, after quenching with MeOH, a series of cationic vinylcarbyne complexes of the general form [Cp(CO)(PPh{sub 3})Mn{triple_bond}C-C(Me){double_bond}C(R)(R{prime})]BF{sub 4}. The cationic alkylidyne complexes [Cp(CO){sub 2}M{triple_bond}C-CH{sub 2}R]{sup +} [M = Re, R = H, M = Mn, R = H, Me, Ph] have been found to undergo facile deprotonation to give the corresponding neutral vinylidene complexes Cp(CO){sub 2}M{double_bond}C{double_bond}C(H)R. The authors have also investigated reactions relevant to the halide promoted Fe and Ru catalyzed carbonylation of nitroaromatics. The final part of this work has involved investigations of metal-oxo complexes.

  18. Triglyceride Metabolism and Hepatic Diseases.

    PubMed

    Fernandez-Mejia, Emptyyn Y

    2013-09-11

    Triglycerides participate in key metabolic functions such as energy storage, thermal insulation and as deposit for essential and non-essential fatty acids that can be used as precursors for the synthesis of structural and functional phospholipids. The liver is a central organ in the regulation of triglyceride metabolism, and it participates in triglyceride synthesis, export, uptake and oxidation. The metabolic syndrome and associated diseases are among the main concerns of public health worldwide. One of the metabolic syndrome components is impaired triglyceride metabolism. Diseases associated with the metabolic syndrome promote the appearance of hepatic alterations e.g., non-alcoholic steatosis, steatohepatitis, fibrosis, cirrhosis and cancer. In this article, we review the molecular actions involved in impaired triglyceride metabolism and its association with hepatic diseases. We discuss mechanisms that reconcile the chronic inflammation and insulin resistance, and new concepts on the role of intestinal micro-flora permeability and proliferation in fatty liver etiology. We also describe the participation of oxidative stress in the progression of events leading from steatosis to steatohepatitis and fibrosis. Finally, we provide information regarding the mechanisms that link fatty acid accumulation during steatosis with changes in growth factors and cytokines that lead to the development of neoplasticcells. One of the main medical concerns vis-à-vishepatic diseases is the lack of symptoms at the onset of the illness and, as result, its late diagnosis. The understandings of the molecular mechanisms that underlie hepatic diseases could help design strategies towards establishing markers for their accurate and timely diagnosis. PMID:24032513

  19. The oncogenic action of ionizing radiation on rat skin. Final progress report, May 1, 1990--April 30, 1992

    SciTech Connect

    Burns, F.J.; Garte, S.J.

    1992-12-31

    The multistage theory of carcinogenesis specifies that cells progress to cancer through a series of discrete, irreversible genetic alterations, but data on radiation-induced cancer incidence in rat skin suggests that an intermediate repairable alteration may occur. Data are presented on cancer induction in rat skin exposed to an electron beam (LET=0.34 keV/{mu}), a neon ion beam (LET=45) or an argon ion beam (LET=125). The rats were observed for tumors at least 78 weeks with squamous and basal cell carcinomas observed. The total cancer yield was fitted by the quadratic equation, and the equation parameters were estimated by linear regression for each type of radiation. Analysis of the DNA from the electron-induced carcinomas indicated that K-ras and/or c-myc oncogenes were activated. In situ hybridization indicated that the cancers contain subpopulations of cells with differing amounts of c-myc and H-ras amplification. The results are consistent with the idea that ionizing radiation produces stable, carcinogenically relevant lesions via 2 repairable events at low LET and via a non-repairable linked event pathway at high LET; either pathway may advance the cell by 1 stage. The proliferative response of rat epidermis following exposure to ionizing radiation was quantified by injection of {sup 14}C-thymidine. The return of these cells to S-phase a second time was detected by a second label ({sup 3}H). When the labeled cells were in G1-phase, the dorsal skin was irradiated with X-rays. All labeling indices were determined. The {sup 14}C labeling index was constant and unaffected by the radiation. The proportion of all cells entering S-phase averaged 3.5% at 18 hr and increased after 44, 52 and 75 hr to average levels of 11.8%, 5. 3%, and 6.6% at 0, 10 and 25 Gy respectively. The proportion of S-phase cells labeled with {sup 14}C increased after 42 hr and remained relatively constant thereafter.

  20. Hybrid solar thermal-photovoltaic systems demonstration, Phase I and II. Final technical progress report, July 5, 1979-December 1982

    SciTech Connect

    Loferski, J.J.

    1983-12-01

    The purpose of the project is to investigate a system based on combined photovoltaic/thermal (PV/T) panels to supply the energy needs of a small single family residence. The system finally selected and constructed uses PV/T panels which utilize air as the heat transfer medium. Optimization of thermal performance was accomplished by attaching metal fins to the back surface of each cell which significantly increased the heat transfer coefficient from the solar cells to the air stream. The other major components of the selected system are an air-to-air heat pump, a rock bin thermal energy storage bin, a synchronous dc-to-ac converter, a microprocessor to control the system, a heat exchanger for the domestic hot water system and of course the building itself which is a one story, well insulated structure having a floor area of 1200 ft/sup 2/. A prototype collector was constructed and tested. Based on this experience, twenty collectors, containing 2860 four inch diameter solar cells, were constructed and installed on the building. Performance of the system was simulated using a TRNSYS-derived program, modified to accommodate PV/T panels and to include the particular components included in the selected system. Simulation of the performance showed that about 65 percent of the total annual energy needs of the building would be provided by the PV/T system. Of this total, about one half is produced at a time when it can be used in the building and one half must be sold back to the utility.

  1. Large experiment data analysis collaboration. Final annual progress report for period November 15, 2000 - April 30, 2002

    SciTech Connect

    Callen, J. D.

    2002-01-14

    Because of the good agreement between theory and experiment (on a number of tokamak experiments) on the nonlinear development, saturation of neoclassical tearing modes (NTMs), the study of NTMs is becoming a mature subject. Thus, our contributions to studies of neoclassical (and regular classical) tearing modes over the past year have focused on a number of particular, more detailed issues: flow shear effects on linear tearing modes, exploring the possibility of NTMs in spherical tokamaks such as NSTX, assisting with classical tearing mode explorations in DIII-D, and fast ion effects on NTMs. In addition, a collaboration with the Institute for Plasma Research group in India was initiated due to their interest in using the NEAR code (developed in part under this grant) to explore neoclassical tearing modes. Finally, a number of talks have been given on basic, current frontier and future extensions of neoclassical tearing mode theory. Our previous identification of the disruption precursor in DIII-D shot 87009 as being due to a global ideal MHD interchange-type instability being driven slowly though its threshold was featured prominently in the DIII-D MHD theory paper at the 2000 IAEA Sorrento meeting. We have also stimulated the application of the NIMROD code to this particular DIII-D disruption precursor and continued to support this code exploration of it. To facilitate quicker evaluations of global-type ideal MHD growth rates and eigenmodes, we have continued our development of a new method for using perturbed equilibria to ''maneuver in delta-W'' space. Since this basic concept for efficiently finding trends in ideal MHD stability using perturbed equilibria has been proven using a screw-pinch geometry, we are now beginning to implement and test the procedure in the GAT0 code for specific DIII-D high beta equilibria. In addition, to analytically explore the ultimate nonlinear evolution of these types of modes, we have begun (primarily on our DOE ''Nonlinear and

  2. Predicting the accumulation of well-metabolized chemicals by fish from measured rates of in vitro intrinsic clearance: Progress made and challenges ahead

    EPA Science Inventory

    Several groups have extrapolated in vitro metabolism data for fish to the intact animal and used this information as an input to models of chemical bioconcentration. These “proof of concept” studies show that incorporating in vitro metabolism data into the models sub...

  3. Final Report: Filling Knowledge Gaps in Biological Networks: Integrated Global Approaches to Understand H{sub 2} Metabolism in Chlamydomonas Reinhardtii

    SciTech Connect

    Grossman, Arthur

    2012-05-01

    The major goal of our part of this project has been to generate mutants in fermentation metabolism and begin to decipher how lesions in the pathways associated with fermentation metabolism impact both H{sub 2} production and the production of other metabolites that accumulate as cells become anoxic. We are also trying to understand how metabolic pathways are regulated as O{sub 2} in the environment becomes depleted.

  4. Beyond the C18 frontier: Androgen and glucocorticoid metabolism in breast cancer tissues: The role of non-typical steroid hormones in breast cancer development and progression.

    PubMed

    McNamara, Keely May; Sasano, Hironobu

    2015-11-01

    Breast cancer's hormonal dependence is well known and has been so for a long time. However in the last two decades great advances have been made in understanding the local metabolism of steroids within tissue. In the form of aromatase inhibition this is already one of the mainstays of breast cancer therapy. This review aims to summarise briefly what is known in terms of the metabolism of C18 steroids but perhaps more importantly to touch on the new developments regarding the importance of the metabolism of androgens and glucocorticoids in breast tissue. It is our hope that this review should provide the reader with a "birds eye view" of the current state of knowledge regarding localised steroid metabolism in the breast. PMID:26057662

  5. ROCK DEFORMATION. Final Progress Report

    SciTech Connect

    2002-05-24

    The Gordon Research Conference (GRC) on ROCK DEFORMATION was held at II Ciocco from 5/19/02 thru 5/24/02. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.

  6. Organometallic Chemistry. Final Progress Report

    SciTech Connect

    2003-07-14

    The Gordon Research Conference (GRC) on Organometallic Chemistry was held at Salve Regina, Newport, Rhode Island, 7/21-26/02. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.

  7. "Target-Site" Drug Metabolism and Transport.

    PubMed

    Foti, Robert S; Tyndale, Rachel F; Garcia, Kristine L P; Sweet, Douglas H; Nagar, Swati; Sharan, Satish; Rock, Dan A

    2015-08-01

    The recent symposium on "Target-Site" Drug Metabolism and Transport that was sponsored by the American Society for Pharmacology and Experimental Therapeutics at the 2014 Experimental Biology meeting in San Diego is summarized in this report. Emerging evidence has demonstrated that drug-metabolizing enzyme and transporter activity at the site of therapeutic action can affect the efficacy, safety, and metabolic properties of a given drug, with potential outcomes including altered dosing regimens, stricter exclusion criteria, or even the failure of a new chemical entity in clinical trials. Drug metabolism within the brain, for example, can contribute to metabolic activation of therapeutic drugs such as codeine as well as the elimination of potential neurotoxins in the brain. Similarly, the activity of oxidative and conjugative drug-metabolizing enzymes in the lung can have an effect on the efficacy of compounds such as resveratrol. In addition to metabolism, the active transport of compounds into or away from the site of action can also influence the outcome of a given therapeutic regimen or disease progression. For example, organic anion transporter 3 is involved in the initiation of pancreatic β-cell dysfunction and may have a role in how uremic toxins enter pancreatic β-cells and ultimately contribute to the pathogenesis of gestational diabetes. Finally, it is likely that a combination of target-specific metabolism and cellular internalization may have a significant role in determining the pharmacokinetics and efficacy of antibody-drug conjugates, a finding which has resulted in the development of a host of new analytical methods that are now used for characterizing the metabolism and disposition of antibody-drug conjugates. Taken together, the research summarized herein can provide for an increased understanding of potential barriers to drug efficacy and allow for a more rational approach for developing safe and effective therapeutics. PMID:25986849

  8. New paradigms for metabolic modeling of human cells.

    PubMed

    Mardinoglu, Adil; Nielsen, Jens

    2015-08-01

    Abnormalities in cellular functions are associated with the progression of human diseases, often resulting in metabolic reprogramming. GEnome-scale metabolic Models (GEMs) have enabled studying global metabolic reprogramming in connection with disease development in a systematic manner. Here we review recent work on reconstruction of GEMs for human cell/tissue types and cancer, and the use of GEMs for identification of metabolic changes occurring in response to disease development. We further discuss how GEMs can be used for the development of efficient therapeutic strategies. Finally, challenges in integration of cell/tissue models for simulation of whole body functions as well as integration of GEMs with other biological networks for generating complete cell/tissue models are presented. PMID:25559199

  9. Metabolic studies of neptunium in the adult baboon: retention, distribution, kinetics, and enhanced excretion by chelation therapy. Technical progress report summary

    SciTech Connect

    Not Available

    1984-01-01

    These investigations provided additional data on the uptake, distribution, retention and excretion of Np-237, Np-239 and Pa-233 in baboons following single intravenous or gavage administration. The influence of oxidation state, chemical medium, pH, mass, etc. on the metabolism of these radionuclides is related.

  10. Inflammasomes and metabolic disease.

    PubMed

    Henao-Mejia, Jorge; Elinav, Eran; Thaiss, Christoph A; Flavell, Richard A

    2014-01-01

    Innate immune response pathways and metabolic pathways are evolutionarily conserved throughout species and are fundamental to survival. As such, the regulation of whole-body and cellular metabolism is intimately integrated with immune responses. However, the introduction of new variables to this delicate evolutionarily conserved physiological interaction can lead to deleterious consequences for organisms as a result of inappropriate immune responses. In recent decades, the prevalence and incidence of metabolic diseases associated with obesity have dramatically increased worldwide. As a recently acquired human characteristic, obesity has exposed the critical role of innate immune pathways in multiple metabolic pathophysiological processes. Here, we review recent evidence that highlights inflammasomes as critical sensors of metabolic perturbations in multiple tissues and their role in the progression of highly prevalent metabolic diseases. PMID:24274736

  11. Metabolism throughout follicle and oocyte development in mammals.

    PubMed

    Collado-Fernandez, Esther; Picton, Helen M; Dumollard, Rémi

    2012-01-01

    Metabolic studies of mammalian embryos started with the development of in vitro culture systems more than 40 years ago. More recently, metabolic studies have begun to shed light on the requirements of growing oocytes/follicles from the earliest stages of folliculogenesis. While growing oocytes preferentially metabolise pyruvate over glucose, the somatic compartment of ovarian follicles is more glycolytic. The metabolic preferences of the oocyte are reflected in the early zygote, which becomes increasingly dependent on glycolytic energy production as development progresses to the blastocyst stage. Furthermore, the intricate metabolic relationship between each oocyte and its somatic surroundings is critical for oocyte growth and developmental competence. Measurements of amino acid turnover in bovine oocytes indicate that glutamine, arginine and leucine are consistently depleted, while alanine is produced, showing similarities with amino acid turnover in preimplantation embryos. Amino acid profiling is a good predictor of embryo quality and might also turn out to be a predictor of oocyte developmental competence. Finally, recent studies have uncovered lipid metabolism in oocytes and early embryos, suggesting that endogenous fatty acids might be used for energy production. Together, metabolic studies have revealed the multiplicity of energetic substrates used by oocytes and early embryos, and suggest that the versatility of the metabolic pathways available for energy production is key for high developmental potential. Metabolic studies of early embryos are now being applied to follicle culture, and the goal of describing the metabolome of the growing oocyte in its follicle is now very attainable. PMID:23417402

  12. Dissolved organic matter and lake metabolism: Biogeochemistry and controls of nutrient flux dynamics to fresh waters. Technical progress report, January 1, 1990--December 31, 1991

    SciTech Connect

    Wetzel, R.G.

    1992-12-31

    The land-water interface region consists of two major components: the wetland, and the down-gradient adjacent littoral floating-leaved and submersed, macrophyte communities. Because of the importance of very high production and nutrient turnover of attached microbiota, a major emphasis of this investigation was placed upon these biota and their metabolic capacities for assimilation and release of organic compounds and nutrient retention and cycling. Examination of the capacities of wetland littoral communities to regulate fluxes of nutrients and organic compounds often has been limited to input-output analyses. These input-output data are an integral part of these investigations, but most of the research effort concentrated on the biotic and metabolic mechanisms that control fluxes and retention capacities and their effects upon biota in the down-gradient waters. The important regulatory capacities of dissolved organic compounds on enzyme reactivity was examined experimentally and coupled to the wetland-littoral organic carbon flux budgets.

  13. Lipid metabolic reprogramming in cancer cells

    PubMed Central

    Beloribi-Djefaflia, S; Vasseur, S; Guillaumond, F

    2016-01-01

    Many human diseases, including metabolic, immune and central nervous system disorders, as well as cancer, are the consequence of an alteration in lipid metabolic enzymes and their pathways. This illustrates the fundamental role played by lipids in maintaining membrane homeostasis and normal function in healthy cells. We reviewed the major lipid dysfunctions occurring during tumor development, as determined using systems biology approaches. In it, we provide detailed insight into the essential roles exerted by specific lipids in mediating intracellular oncogenic signaling, endoplasmic reticulum stress and bidirectional crosstalk between cells of the tumor microenvironment and cancer cells. Finally, we summarize the advances in ongoing research aimed at exploiting the dependency of cancer cells on lipids to abolish tumor progression. PMID:26807644

  14. Fundamentals of cancer metabolism.

    PubMed

    DeBerardinis, Ralph J; Chandel, Navdeep S

    2016-05-01

    Tumors reprogram pathways of nutrient acquisition and metabolism to meet the bioenergetic, biosynthetic, and redox demands of malignant cells. These reprogrammed activities are now recognized as hallmarks of cancer, and recent work has uncovered remarkable flexibility in the specific pathways activated by tumor cells to support these key functions. In this perspective, we provide a conceptual framework to understand how and why metabolic reprogramming occurs in tumor cells, and the mechanisms linking altered metabolism to tumorigenesis and metastasis. Understanding these concepts will progressively support the development of new strategies to treat human cancer. PMID:27386546

  15. Fundamentals of cancer metabolism

    PubMed Central

    DeBerardinis, Ralph J.; Chandel, Navdeep S.

    2016-01-01

    Tumors reprogram pathways of nutrient acquisition and metabolism to meet the bioenergetic, biosynthetic, and redox demands of malignant cells. These reprogrammed activities are now recognized as hallmarks of cancer, and recent work has uncovered remarkable flexibility in the specific pathways activated by tumor cells to support these key functions. In this perspective, we provide a conceptual framework to understand how and why metabolic reprogramming occurs in tumor cells, and the mechanisms linking altered metabolism to tumorigenesis and metastasis. Understanding these concepts will progressively support the development of new strategies to treat human cancer. PMID:27386546

  16. Hepatic diseases related to triglyceride metabolism.

    PubMed

    Aguilera-Méndez, Asdrubal; Álvarez-Delgado, Carolina; Hernández-Godinez, Daniel; Fernandez-Mejia, Cristina

    2013-10-01

    Triglycerides participate in key metabolic functions such as energy storage, thermal insulation and as deposit for essential and non-essential fatty acids that can be used as precursors for the synthesis of structural and functional phospholipids. The liver is a central organ in the regulation of triglyceride metabolism, and it participates in triglyceride synthesis, export, uptake and oxidation. The metabolic syndrome and associated diseases are among the main concerns of public health worldwide. One of the metabolic syndrome components is impaired triglyceride metabolism. Diseases associated with the metabolic syndrome promote the appearance of hepatic alterations e.g., non-alcoholic steatosis, steatohepatitis, fibrosis, cirrhosis and cancer. In this article, we review the molecular actions involved in impaired triglyceride metabolism and its association with hepatic diseases. We discuss mechanisms that reconcile the chronic inflammation and insulin resistance, and new concepts on the role of intestinal micro-flora permeability and proliferation in fatty liver etiology. We also describe the participation of oxidative stress in the progression of events leading from steatosis to steatohepatitis and fibrosis. Finally, we provide information regarding the mechanisms that link fatty acid accumulation during steatosis with changes in growth factors and cytokines that lead to the development of neoplastic cells. One of the main medical concerns vis-a-vis hepatic diseases is the lack of symptoms at the onset of the illness and, as result, its late diagnosis. The understandings of the molecular mechanisms that underlie hepatic diseases could help design strategies towards establishing markers for their accurate and timely diagnosis. PMID:24059726

  17. Metabolic neuropathies

    MedlinePlus

    Neuropathy - metabolic ... can be caused by many different things. Metabolic neuropathy may be caused by: A problem with the ... one of the most common causes of metabolic neuropathies. People who are at the highest risk for ...

  18. 5MeCDDO Blocks Metabolic Activation but not Progression of Breast, Intestine, and Tongue Cancers. Is Antioxidant Response Element a Prevention Target?

    PubMed

    Lubet, Ronald A; Townsend, Reid; Clapper, Margie L; Juliana, M Margaret; Steele, Vernon E; McCormick, David L; Grubbs, Clinton J

    2016-07-01

    The preventive efficacy of the triterpenoid 5MeCDDO was tested in two models of mammary cancer, the Min model of intestinal cancer, and a chemically induced model of head and neck cancer. In one model of mammary cancer, female Sprague-Dawley rats were administered MNU at 50 days of age, and 5MeCDDO (27 ppm) was administered in the diet beginning 5 days later for the duration of the study; 5MeCDDO was ineffective. In contrast, in a model examining initiation of mammary cancers by the procarcinogen dimethyl-benzanthracene, 5, 6-benzoflavone (500 ppm, an Ah receptor agonist) or 5MeCDDO (27 or 2.7 ppm) decreased tumor multiplicity by 90%, 80%, and 50%, respectively. This anti-initiating effect which is presumably mediated by altered metabolic activation parallels our observation that 5MeCDDO induced proteins of various antioxidant response element (ARE)-related phase II drug-metabolizing enzymes [e.g., GST Pi, AKR 7A3 (aflatoxicol), epoxide hydrolase, and quinone reductase] in the liver. 5MeCDDO tested in the 4-nitroquinoline-l-oxide (4-NQO) head and neck cancer model failed to decrease tumor incidence or invasiveness. In the Min mouse model of intestinal cancer, a high dose of 5MeCDDO (80 ppm) was weakly effective in reducing adenoma multiplicity [∼30% (P < 0.05)]; however, a lower dose was totally ineffective. These findings question whether measuring increased levels of certain ARE-related genes (e.g., quinone reductase, GST Pi), indicating decreased carcinogen activation are sufficient to imply general chemopreventive efficacy of a given agent or mixture. Cancer Prev Res; 9(7); 616-23. ©2016 AACR. PMID:27150634

  19. Effects of exercise training in the elderly: impact of progressive- resistance training on skeletal muscle and whole-body protein metabolism.

    PubMed

    Fielding, R A

    1995-11-01

    The declines in functional capacity and muscle function with advancing age are well-documented. In addition, it appears that the age-related changes in body composition have profound effects on functional capacity and nutrient requirements. The overwhelming evidence presented in the present review suggests that the loss of muscle strength and function observed with advancing age is reversible even in the frail elderly. Along with the profound functional improvement in older individuals in response to progressive-resistance training, several studies have reported increases in resting energy expenditure and increased requirements for dietary protein. Exercise programmes designed to improve muscle strength be recommended for older individuals as an effective countermeasure to the sarcopenia of old age. PMID:8643704

  20. Energetics of end product excretion in anaerobic bacteria and the metabolism of fatty acids by Syntrophomonas wolfei: Progress report, November 16, 1986-November 15, 1987

    SciTech Connect

    McInerney, M.J.

    1987-01-01

    We have studied the growth and metabolism of Syntrophomonas wolfei in pure culture with crotonate as the energy source. S. wolfei grows in crotonate mineral salts medium without rumen fluid with cobalamin, thymine, lipoic acid and biotin added. However, after four to six transfers in this medium, growth ceases, indicating that another vitamin is required. The chemically defined medium allows large batches of S. wolfei to be grown for enzyme purification. All the enzymes involved in the oxidation of crotonyl-CoA to acetate have been detected. The pure culture of S. wolfei or coculture of S. wolfei grown with crotonate contain high activities of a crotonate: acetyl-CoA CoA-transferase activity. This activity is not detected in cocultures grown with butyrate. Thus, we believe that the reason why S. wolfei can now grow with crotonate is that an alteration or mutation occurred which allows the organism to activate this crotonate. S. wolfei also makes small amounts of H/sub 2/ when grown in pure culture with crotonate. A methyl viologen-dependent hydrogenase activity was found. We have also demonstrated the production of H/sub 2/ from 3-hydroxybutyryl-CoA in cell-free extracts of S. wolfei by coupling H/sub 2/ production to CH/sub 4/ production with the addition of Methanobacterium bryantii and directly using a hydrogen electrode. These results clearly show that S. wolfei makes H/sub 2/. S. wolfei does not contain formate dehydrogenase or CO dehydrogenase activities.

  1. Dissolved organic matter and lake metabolism: Biogeochemistry and controls of nutrient flux dynamics in lakes: Technical progress report, 1 July 1987--30 June 1988

    SciTech Connect

    Wetzel, R.G.

    1988-01-01

    Our work has continued and expanded in the region of nutrient fluxes, uptake mechanisms, and recycling in microcommunities on the plants and within the plants. Limiting nutrient factors are dissolved inorganic carbon, phosphorus, and in some cases, nitrogen. The macrophyte-epiphyte complex exists in a viscous medium where regions of greatly reduced flow and no turbulence occur at surfaces. As a result of the greatly reduced flow, lack of turbulence,and extremely slow rate of diffusion in water, diffusional processes predominate within the boundary layer. During periods of high metabolic activity (i.e., during photosynthesis) nutrients are likely to become depleted within the boundary layer, constraining production and placing the macrophyte and associated microflora in direct nutrient competition. Once nutrients have entered the complex via diffusion or sedimentation from the bulk phase, or uptake through the macrophyte rhizosphere, exit across the boundary layer is retarded. The close juxtaposition of the biota results in a rapid cycling and, ultimately, in concentration of nutrients. This occurs until the end of the macrophyte vegetative life span when the supporting macrophyte loses its integrity and release of dissolved matter exceeds the retentive capacity of the microbiota. A quantity of this material released by the macrophyte is retained in the epiphyton when the macrophyte-epiphyte complex sinks to the sediment. 324 refs., 6 figs.

  2. Simultaneous metabolism of chloro- and methyl-aromatic compounds by selected bacterial strains. Final report, 20 August 1991-19 August 1992

    SciTech Connect

    Focht, D.D.

    1993-05-27

    Microorganisms are frequently able to degrade anthropogenic materials using pathways that evolved for the assimilation of related naturally-occurring compounds. Complications can arise, however, during the metabolism of mixtures when incompatible intermediates are formed from different components. The breakdown of chloro- and methyl-aromatics, for example, produces catechols which are oxidized differently: chlorocatechols are normally cleaved by ortho fission and methylcatechols by meta fission. If both systems act simultaneously, suicide substrates or dead-end metabolites are usually formed. Nevertheless, bacteria differ in their, ability to cope with such mixtures. A unique bacterium, Pseudomonas cepacia MB2 was isolated by selective enrichment on 2-methylbenzoate, yet was also able to fortuitously utilize 3-chloro-2-methylbenzoate as a sole carbon source. This strain is unique in its ability to utilize an aromatic acid containing both a methyl and chloro substituent via the metafission pathway without the production of suicidal products.

  3. Disorders of Carbohydrate Metabolism

    MedlinePlus

    ... Metabolic Disorders Disorders of Carbohydrate Metabolism Disorders of Amino Acid Metabolism Disorders of Lipid Metabolism Carbohydrates are sugars. ... Metabolic Disorders Disorders of Carbohydrate Metabolism Disorders of Amino Acid Metabolism Disorders of Lipid Metabolism NOTE: This is ...

  4. The gut microbiota modulates host amino acid and glutathione metabolism in mice.

    PubMed

    Mardinoglu, Adil; Shoaie, Saeed; Bergentall, Mattias; Ghaffari, Pouyan; Zhang, Cheng; Larsson, Erik; Bäckhed, Fredrik; Nielsen, Jens

    2015-10-01

    The gut microbiota has been proposed as an environmental factor that promotes the progression of metabolic diseases. Here, we investigated how the gut microbiota modulates the global metabolic differences in duodenum, jejunum, ileum, colon, liver, and two white adipose tissue depots obtained from conventionally raised (CONV-R) and germ-free (GF) mice using gene expression data and tissue-specific genome-scale metabolic models (GEMs). We created a generic mouse metabolic reaction (MMR) GEM, reconstructed 28 tissue-specific GEMs based on proteomics data, and manually curated GEMs for small intestine, colon, liver, and adipose tissues. We used these functional models to determine the global metabolic differences between CONV-R and GF mice. Based on gene expression data, we found that the gut microbiota affects the host amino acid (AA) metabolism, which leads to modifications in glutathione metabolism. To validate our predictions, we measured the level of AAs and N-acetylated AAs in the hepatic portal vein of CONV-R and GF mice. Finally, we simulated the metabolic differences between the small intestine of the CONV-R and GF mice accounting for the content of the diet and relative gene expression differences. Our analyses revealed that the gut microbiota influences host amino acid and glutathione metabolism in mice. PMID:26475342

  5. The gut microbiota modulates host amino acid and glutathione metabolism in mice

    PubMed Central

    Mardinoglu, Adil; Shoaie, Saeed; Bergentall, Mattias; Ghaffari, Pouyan; Zhang, Cheng; Larsson, Erik; Bäckhed, Fredrik; Nielsen, Jens

    2015-01-01

    The gut microbiota has been proposed as an environmental factor that promotes the progression of metabolic diseases. Here, we investigated how the gut microbiota modulates the global metabolic differences in duodenum, jejunum, ileum, colon, liver, and two white adipose tissue depots obtained from conventionally raised (CONV-R) and germ-free (GF) mice using gene expression data and tissue-specific genome-scale metabolic models (GEMs). We created a generic mouse metabolic reaction (MMR) GEM, reconstructed 28 tissue-specific GEMs based on proteomics data, and manually curated GEMs for small intestine, colon, liver, and adipose tissues. We used these functional models to determine the global metabolic differences between CONV-R and GF mice. Based on gene expression data, we found that the gut microbiota affects the host amino acid (AA) metabolism, which leads to modifications in glutathione metabolism. To validate our predictions, we measured the level of AAs and N-acetylated AAs in the hepatic portal vein of CONV-R and GF mice. Finally, we simulated the metabolic differences between the small intestine of the CONV-R and GF mice accounting for the content of the diet and relative gene expression differences. Our analyses revealed that the gut microbiota influences host amino acid and glutathione metabolism in mice. PMID:26475342

  6. Experimental verification of a progressive damage model for composite laminates based on continuum damage mechanics. M.S. Thesis Final Report

    NASA Technical Reports Server (NTRS)

    Coats, Timothy William

    1994-01-01

    Progressive failure is a crucial concern when using laminated composites in structural design. Therefore the ability to model damage and predict the life of laminated composites is vital. The purpose of this research was to experimentally verify the application of the continuum damage model, a progressive failure theory utilizing continuum damage mechanics, to a toughened material system. Damage due to tension-tension fatigue was documented for the IM7/5260 composite laminates. Crack density and delamination surface area were used to calculate matrix cracking and delamination internal state variables, respectively, to predict stiffness loss. A damage dependent finite element code qualitatively predicted trends in transverse matrix cracking, axial splits and local stress-strain distributions for notched quasi-isotropic laminates. The predictions were similar to the experimental data and it was concluded that the continuum damage model provided a good prediction of stiffness loss while qualitatively predicting damage growth in notched laminates.

  7. Metabolic Dysfunction in Pulmonary Hypertension: The Expanding Relevance of the Warburg Effect

    PubMed Central

    Cottrill, Katherine A.; Chan, Stephen Y.

    2013-01-01

    Background Pulmonary hypertension (PH) is an enigmatic vascular syndrome characterized by increased pulmonary arterial pressure and adverse remodeling of the pulmonary arterioles and often of the right ventricle. Drawing parallels with tumorigenesis, recent endeavors have explored the relationship between metabolic dysregulation and PH pathogenesis. Design We will discuss the general mechanisms by which cellular stressors such as hypoxia and inflammation alter cellular metabolism. Based on those principles, we will explore the development of a corresponding metabolic pathophenotype in PH, with a focus on WHO groups I and III, and the implications that these alterations may have for future treatment of this disease. Results Investigation of metabolic dysregulation in both the pulmonary vasculature and right ventricle during PH pathogenesis has provided a more unifying understanding of how disparate disease triggers coordinate end-stage disease manifestations. Namely, as defined originally in various cancers, the Warburg effect describes a chronic shift in energy production from mitochondrial oxidative phosphorylation to glycolysis. In many cases, this Warburg phenotype may serve as a central causative mechanism for PH progression, largely driving cellular hyperproliferation and resistance to apoptosis. Consequently, new therapeutic strategies have been increasingly pursued that target the Warburg phenotype. Finally, new technologies are increasingly becoming available to probe more completely the complexities of metabolic cellular reprogramming and may reveal distinct metabolic pathways beyond the Warburg effect that drive PH. Conclusion Studies of metabolic dysregulation in PH are just emerging but may offer powerful therapeutic means to prevent or even reverse disease progression at the molecular level. PMID:23617881

  8. Dysregulated metabolism contributes to oncogenesis.

    PubMed

    Hirschey, Matthew D; DeBerardinis, Ralph J; Diehl, Anna Mae E; Drew, Janice E; Frezza, Christian; Green, Michelle F; Jones, Lee W; Ko, Young H; Le, Anne; Lea, Michael A; Locasale, Jason W; Longo, Valter D; Lyssiotis, Costas A; McDonnell, Eoin; Mehrmohamadi, Mahya; Michelotti, Gregory; Muralidhar, Vinayak; Murphy, Michael P; Pedersen, Peter L; Poore, Brad; Raffaghello, Lizzia; Rathmell, Jeffrey C; Sivanand, Sharanya; Vander Heiden, Matthew G; Wellen, Kathryn E

    2015-12-01

    Cancer is a disease characterized by unrestrained cellular proliferation. In order to sustain growth, cancer cells undergo a complex metabolic rearrangement characterized by changes in metabolic pathways involved in energy production and biosynthetic processes. The relevance of the metabolic transformation of cancer cells has been recently included in the updated version of the review "Hallmarks of Cancer", where dysregulation of cellular metabolism was included as an emerging hallmark. While several lines of evidence suggest that metabolic rewiring is orchestrated by the concerted action of oncogenes and tumor suppressor genes, in some circumstances altered metabolism can play a primary role in oncogenesis. Recently, mutations of cytosolic and mitochondrial enzymes involved in key metabolic pathways have been associated with hereditary and sporadic forms of cancer. Together, these results demonstrate that aberrant metabolism, once seen just as an epiphenomenon of oncogenic reprogramming, plays a key role in oncogenesis with the power to control both genetic and epigenetic events in cells. In this review, we discuss the relationship between metabolism and cancer, as part of a larger effort to identify a broad-spectrum of therapeutic approaches. We focus on major alterations in nutrient metabolism and the emerging link between metabolism and epigenetics. Finally, we discuss potential strategies to manipulate metabolism in cancer and tradeoffs that should be considered. More research on the suite of metabolic alterations in cancer holds the potential to discover novel approaches to treat it. PMID:26454069

  9. Rapidly Progressive Dementia

    PubMed Central

    Geschwind, Michael D.; Shu, Huidy; Haman, Aissa; Sejvar, James J.; Miller, Bruce L.

    2009-01-01

    In contrast with more common dementing conditions that typically develop over years, rapidly progressive dementias can develop subacutely over months, weeks, or even days and be quickly fatal. Because many rapidly progressive dementias are treatable, it is paramount to evaluate and diagnose these patients quickly. This review summarizes recent advances in the understanding of the major categories of RPD and outlines efficient approaches to the diagnosis of the various neurodegenerative, toxic-metabolic, infectious, autoimmune, neoplastic, and other conditions that may progress rapidly. PMID:18668637

  10. Federal Assistance Program Quarterly Project Progress Report. Geothermal Energy Program: Information Dissemination, Public Outreach, and Technical Analysis Activities. Reporting Period: January 1 - March 31, 2001 [Final report

    SciTech Connect

    Lund, John W.

    2002-03-22

    The final report of the accomplishments of the geothermal energy program: information dissemination, public outreach and technical analysis activities by the project team consisting of the Geo-Heat Center, Geothermal Resources Council, Geothermal Education Office, Geothermal Energy Association and the Washington State University Energy Program.

  11. Biophysical techniques for examining metabolic, proliferative, and genetic effects of microwave radiation. Final report, 1 Oct 89-30 Aug 90

    SciTech Connect

    Meltz, M.L.

    1991-09-01

    This project was undertaken to prepare for a comprehensive research effort examining metabolic, proliferative, and genetic effects of microwave radiation. To accomplish this task, preliminary studies have been performed with 4 cells systems; Chinese hamster ovary (CHO) cells, AS52 Chinese hamster cells (heterozygous at the xanthine-guanine phosphoribosyl transferase (XGPRT) locus), 244B proliferating human lymphoblastoid cells, and freshly isolated peripheral lymphocytes. The thermal response of the 244B cells has been carefully examined, and an initial characterization of the membrane markers, membrane permeability, and cell cycle distribution of these cells undertaken. The absence of the induction of chromosome aberrations in CHO cells, after exposure to 850 MHz pulsed wave (PW), 18mW/cm2 (specific absorption rate (SAR) 14.4 W/kg) radiofrequency radiation (RFR), or after exposure to 1,200 MHz PW (220 W -300 W) net forward power; SAR 24.33 W/kg RFR, is reported. The survival response of the AS52 cells, after simultaneous treatment at 37 C or 40 C, with and without mitomycin or adriamycin, is described. The survival of the AS52 cells after X-ray exposure at low and high dose rates is also described.

  12. Effects of organophosphorus anticholinesterase compounds on brain glucose and energy metabolism. Final summary report, 1 October 1981-29 February 1984

    SciTech Connect

    Medina, M.A.; Miller, A.L.

    1984-09-01

    The effects of Soman and paraoxon on cerebral metabolic rate (CMRg) and the levels of various metabolites in rate brain were investigated. In non-convulsing animals, 0.8 of the paraoxon LD50 and 0.5 of the Soman LD50 tended to lower CMRg. A higher dose of Soman, 0.8-0.95 of the LD50, resulted in convulsive seizures in some but not all of the animals. In convulsing rats the CMRg and lactate levels were elevated primarily in the cortex and thalamus/basal ganglia. Decreased ATP and glucose levels with an elevated CMRg and lactate concentration was observed in the cortex, suggesting that Soman may be uncoupling oxidative phosphorylation. Pretreatment with atropine prevented the behavioral manifestations and the elevated CMRg but not the hyperglycemia produced by an 0.8 LD50 dose of Soman. These results suggest that Soman-induced convulsions are similar to those produced by other central nervous system (CNS) excitatory agents in that only certain brain regions are affected. The use of atropine to block the CNS disturbances produced by Soman appears to be effective also does not result in the extensive depression of CMRg observed with TAB, a mixture of trimedoxime, atropine and benactyzine.

  13. Metabolic Disorders

    MedlinePlus

    ... as your liver, muscles, and body fat. A metabolic disorder occurs when abnormal chemical reactions in your body ... that produce the energy. You can develop a metabolic disorder when some organs, such as your liver or ...

  14. Toxic and Metabolic Myelopathies.

    PubMed

    Ramalho, Joana; Nunes, Renato Hoffmann; da Rocha, Antonio José; Castillo, Mauricio

    2016-10-01

    Myelopathy describes any neurologic deficit related to the spinal cord. It is most commonly caused by its compression by neoplasms, degenerative disc disease, trauma, or infection. Less common causes of myelopathy include spinal cord tumors, infection, inflammatory, neurodegenerative, vascular, toxic, and metabolic disorders. Conditions affecting the spinal cord must be recognized as early as possible to prevent progression that may lead to permanent disability. Biopsy is rarely performed, thus the diagnosis and management rely on patient׳s history, physical examination, laboratory results, and imaging findings. Here we review the clinical presentations, pathophysiological mechanisms, and magnetic resonance imaging findings of myelopathies related to metabolic or toxic etiologies. PMID:27616316

  15. Metabolic Constraints on the Eukaryotic Transition

    NASA Astrophysics Data System (ADS)

    Wallace, Rodrick

    2009-04-01

    Mutualism, obligate mutualism, symbiosis, and the eukaryotic ‘fusion’ of Serial Endosymbiosis Theory represent progressively more rapid and less distorted real-time communication between biological structures instantiating information sources. Such progression in accurate information transmission requires, in turn, progressively greater channel capacity that, through the homology between information source uncertainty and free energy density, requires ever more energetic metabolism. The eukaryotic transition, according to this model, may have been entrained by an ecosystem resilience shift from anaerobic to aerobic metabolism.

  16. Field evaluation of gas-lift and progressive-cavity pumps as effective dewatering methods for coalbed methane wells. Final report, April 1984-December 1985

    SciTech Connect

    Graves, S.L.; Hollingsworth, F.C.; Beavers, W.M.

    1986-03-01

    Field evaluations of gas-lift and progressive-cavity pumps were conducted to determine their effectiveness as dewatering techniques for coalbed-methane wells in the Warrior Coal Field. AMPCO installed a gas-lift system in AMPCO Well No. 6. Problems included poor performance of all gas-lift valve designs and higher instantaneous water production rates than anticipated due to heading and unloading. The test provided the conclusion that gas lift is an effective start-up dewatering tool for initial removal of large amounts of water and solids but that in use as a long-term dewatering tool, needs additional evaluation relative to capital cost, valve design, and extended performance.

  17. Final report, Feedback limitations of photosynthesis

    SciTech Connect

    Sharkey, Thomas D.

    1999-07-22

    Final report of research on carbon metabolism of photosynthesis. The feedback from carbon metabolism to primary photosynthetic processes is summarized, and a comprehensive list of published scientific papers is provided.

  18. Analysis and control of the METC fluid bed gasifier. Final report (includes technical progress report for October 1994--January 1995), September 1994--September 1996

    SciTech Connect

    1996-09-01

    This document presents a modeling and control study of the Fluid Bed Gasification (FBG) unit at the Morgantown Energy Technology Center (METC). The work is performed under contract no. DE-FG21-94MC31384. The purpose of this study is to generate a simple FBG model from process data, and then use the model to suggest an improved control scheme which will improve operation of the gasifier. The work first developes a simple linear model of the gasifier, then suggests an improved gasifier pressure and MGCR control configuration, and finally suggests the use of a multivariable control strategy for the gasifier.

  19. Recovery of valuable chlorosilane intermediates by a novel waste conversion process. Technical report for phase IIIA (final) and phase IIIB (progress)

    SciTech Connect

    Anderson, K.E.

    1998-10-01

    From July 1994 through May 1998, direct process residue (DPR) hydrogenolysis has been studied in the laboratory, at a small Pilot Plant, and finally at a larger Pilot Plant within Dow Corning`s Carrollton, Kentucky plant. The system reacts filtered DPR with monomer at high temperature and pressure. The process demonstrates DPR conversion up to 86%. The reaction product contains high concentrations of valuable monomers such as dimethyldichlorosilane and methyldichlorosilane. A larger DPR hydrogenolysis reactor based on these results is being designed for operation in Europe at Dow Corning`s Barry, Wales site.

  20. Nuclear Island Engineering MHTGR [Modular High-Temperature Gas-cooled Reactor] preliminary and final designs. Technical progress report, December 12, 1988--September 30, 1989

    SciTech Connect

    1989-12-01

    This report summarizes the Department of Energy (DOE)-funded work performed by General Atomics (GA) under the Nuclear Island Engineering (NIE)-Modular High-Temperature Gas-cooled Reactor (MHTGR) Preliminary and Final Designs Contract DE-AC03-89SF17885 for the period December 12, 1988 through September 30, 1989. This reporting period is the first (partial) fiscal year of the 5-year contract performance period. The objective of DOE`s MHTGR program is to advance the design from the conceptual design phase into preliminary design and then on to final design in support of the Nuclear Regulatory Commission`s (NRC`s) design review and approval of the MHTGR Design Team, is focused on the Nuclear Island portion of the technology and design, primarily in the areas of the reactor and internals, fuel characteristics and fuel fabrication, helium services systems, reactor protection, shutdown cooling, circulator design, and refueling system. Maintenance and implementation of the functional methodology, plant-level analysis, support for probabilistic risk assessment, quality assurance, operations, and reliability/availability assessments are included in GA`s scope of work.

  1. Intelligent distributed control for nuclear power plants. Final (third annual) technical progress report, September 1991--June 1993 (September 1989--June 1993): Includes no-cost extension period from September 1992--June 1993

    SciTech Connect

    Klevans, E.H.

    1993-12-31

    This project was initiated in September 1989 as a three year project to develop and demonstrate Intelligent Distributed Control (IDC) for Nuclear Power Plants. There were two primary goals of this research project. The first goal was to combine diagnostics and control to achieve a highly automated power plant as described by M.A. Schultz. The second goal was to apply this research to develop a prototype demonstration on an actual power plant system, the EBR-2 steam plant. Described in this Final (Third Annual) Technical Progress Report is the accomplishment of the project`s final milestone, an in-plant intelligent control experiment conducted on April 1, 1993. The development of the experiment included: simulation validation, experiment formulation and final programming, procedure development and approval, and experimental results. Other third year developments summarized in this report are: (1) a theoretical foundation for Reconfigurable Hybrid Supervisory Control, (2) a steam plant diagnostic system, (3) control console design tools and (4) other advanced and intelligent control.

  2. Simultaneous high-temperature removal of alkali and particulates in a pressurized gasification system. Final technical progress report, October 1978-October 1980

    SciTech Connect

    Mulik, P.R.; Ciliberti, D.F.; Alvin, M.A.; Ahmed, M.M.; Bachovchin, D.M.; Keairns, D.L.

    1981-02-01

    This final project report summarizes the results of extensive thermodynamic and preliminary experimental studies that have identified the use of aluminosilicate materials for simultaneously removing volatile alkali and particulate released during pressurized gasification of coal. The gettering capacity of three selected materials has been evaluated in a bench-scale reactor operating at 1114 kPa total pressure and 1123 to 1173 K in alkali-laden inert and simulated fuel gas environments. At 1123 K alkali gettering results through insoluble complexes, while at 1173 K saturation of the insoluble complex is completed, with gettering occurring mainly through soluble complexes. The gettering mechanism will be delineated through future thermogravimetric studies in a proposed program extension.

  3. Pelletizing/reslurrying as a means of distributing and firing clean coal. Final quarterly technical progress report No. 7, January 1, 1992-- March 31, 1992

    SciTech Connect

    Conkle, H.N.

    1992-06-09

    Work in this quarter focused on completing (1) the final batch of pilot-scale disk pellets, (2) storage, handling, and transportation evaluation, (3) pellet reslurrying and atomization studies, and (4) cost estimation for pellet and slurry production. Disk pelletization of Elkhorn coal was completed this quarter. Pellets were approximately 1/2- to 3/4-in. in diameter. Pellets, after thermal curing were strong and durable and exceeded the pellet acceptance criteria. Storage and handling tests indicate a strong, durable pellet can be prepared from all coals, and these pellets (with the appropriate binder) can withstand outdoor, exposed storage for at least 4 weeks. Pellets in unexposed storage show no deterioration in pellet properties. Real and simulated transportation tests indicate truck transportation should generate less than 5 percent fines during transport. Continuous reslurrying testing and subsequent atomization evaluation were performed this quarter in association with University of Alabama and Jim Walter Resources. Four different slurries of approximately 55-percent-solids with viscosities below 500 cP (at 100 sec{sup {minus}1}) were prepared. Both continuous pellet-to-slurry production and atomization testing was successfully demonstrated. Finally, an in depth evaluation of the cost to prepare pellets, transport, handle, store, and convert the pellet into Coal Water Fuel (CWF) slurries was completed. Cost of the pellet-CWF option are compared with the cost to directly convert clean coal filter cake into slurry and transport, handle and store it at the user site. Findings indicate that in many circumstances, the pellet-CWF option would be the preferred choice. The decision depends on the plant size and transportation distance, and to a lesser degree on the pelletization technique and the coal selected.

  4. Engineering development of coal-fired high performance power systems, Phases 2 and 3. Quarterly progress report, October 1--December 31, 1996. Final report

    SciTech Connect

    1996-12-31

    The goals of this program are to develop a coal-fired high performance power generation system (HIPPS) by the year 2000 that is capable of: {gt} 47% efficiency (HHV); NO{sub x}, SO{sub x}, and particulates {gt} 10% NSPS; coal providing {ge} 65% of heat input; all sold wastes benign; and cost of electricity 90% of present plant. Work reported herein is from Task 1.3 HIPPS Commercial Plant Design, Task 2,2 HITAF Air Heater, and Task 2.4 Duct Heater Design. The impact on cycle efficiency from the integration of various technology advances is presented. The criteria associated with a commercial HIPPS plant design as well as possible environmental control options are presented. The design of the HITAF air heaters, both radiative and convective, is the most critical task in the program. In this report, a summary of the effort associated with the radiative air heater designs that have been considered is provided. The primary testing of the air heater design will be carried out in the UND/EERC pilot-scale furnace; progress to date on the design and construction of the furnace is a major part of this report. The results of laboratory and bench scale activities associated with defining slag properties are presented. Correct material selection is critical for the success of the concept; the materials, both ceramic and metallic, being considered for radiant air heater are presented. The activities associated with the duct heater are also presented.

  5. Exploiting tumor metabolism: challenges for clinical translation

    PubMed Central

    Vander Heiden, Matthew G.

    2013-01-01

    The metabolism of cancer cells differs from most normal cells, but how to exploit this difference for patient benefit is incompletely understood. Cancer cells require altered metabolism to efficiently incorporate nutrients into biomass and support abnormal proliferation. In addition, the survival of tumor cells outside of a normal tissue context requires adaptation of metabolism to different microenvironments. Some existing chemotherapies target metabolic enzymes, and there is a resurgent interest in developing new cancer drugs that interfere with metabolism. Success with this approach depends on understanding why specific metabolic pathways are important for cancer cells, determining how best to select patients, and developing technologies for monitoring patient response to therapies that target metabolic enzymes. The articles in this Review series address these issues, with a focus on how altered metabolism might influence tumor progression and how this knowledge might inform the use of new therapies targeting cancer metabolism. Emerging biomarker strategies to guide drug development are also highlighted. PMID:23999437

  6. Plasma Science Committee (PLSC) and the Panel on Opportunities in Plasma Science and Technology (OPST). Final technical progress report, 1 June 1993--31 May 1994

    SciTech Connect

    1998-12-01

    The Plasma Science Committee (PLSC) of the National Research Council (NRC) is charged with monitoring the health of the field of plasma science in the United States. Accordingly, the Committee identifies and examines both broad and specific issues affecting the field. Regular meetings, teleconferences, briefings from agencies and the scientific community, the formation of study panels to prepare reports, and special symposia are among the mechanisms used by the PLSC to meet its charge. This progress report presents a review of PLSC activities from June 1, 1993 to May 31, 1994. The details of prior activities are discussed in earlier reports. This report also includes the status of activities associated with the PLSC study on opportunities in plasma science and technology. During the above period, the PLSC continued to track and participate in, when requested, discussions on the health of the field. Much of the perspective of the PLSC has been presented in its report Research Briefing on Contemporary Problems in Plasma Science. That report not only has served as the basis for briefings to representatives of the federal government and the community-at-large, but also served as the starting point for the Panel on Opportunities in Plasma Science and Technology (OPST) as it began an assessment of the field. The PLSC also continued its follow-up briefings and discussions on the results of the report Plasma Processing of Materials: Scientific and Technological Opportunities (PPPM). As a result of these activities, the Committee is now working with the NRC Committee on Atomic, Molecular, and Optical Sciences (CAMOS) to organize a symposium on database needs in plasma processing of materials.

  7. Metabolic myopathies

    NASA Technical Reports Server (NTRS)

    Martin, A.; Haller, R. G.; Barohn, R.; Blomqvist, C. G. (Principal Investigator)

    1994-01-01

    Metabolic myopathies are disorders of muscle energy production that result in skeletal muscle dysfunction. Cardiac and systemic metabolic dysfunction may coexist. Symptoms are often intermittent and provoked by exercise or changes in supply of lipid and carbohydrate fuels. Specific disorders of lipid and carbohydrate metabolism in muscle are reviewed. Evaluation often requires provocative exercise testing. These tests may include ischemic forearm exercise, aerobic cycle exercise, and 31P magnetic resonance spectroscopy with exercise.

  8. Scaling metabolic rate fluctuations.

    PubMed

    Labra, Fabio A; Marquet, Pablo A; Bozinovic, Francisco

    2007-06-26

    Complex ecological and economic systems show fluctuations in macroscopic quantities such as exchange rates, size of companies or populations that follow non-Gaussian tent-shaped probability distributions of growth rates with power-law decay, which suggests that fluctuations in complex systems may be governed by universal mechanisms, independent of particular details and idiosyncrasies. We propose here that metabolic rate within individual organisms may be considered as an example of an emergent property of a complex system and test the hypothesis that the probability distribution of fluctuations in the metabolic rate of individuals has a "universal" form regardless of body size or taxonomic affiliation. We examined data from 71 individuals belonging to 25 vertebrate species (birds, mammals, and lizards). We report three main results. First, for all these individuals and species, the distribution of metabolic rate fluctuations follows a tent-shaped distribution with power-law decay. Second, the standard deviation of metabolic rate fluctuations decays as a power-law function of both average metabolic rate and body mass, with exponents -0.352 and -1/4 respectively. Finally, we find that the distributions of metabolic rate fluctuations for different organisms can all be rescaled to a single parent distribution, supporting the existence of general principles underlying the structure and functioning of individual organisms. PMID:17578913

  9. Metabolic ecology.

    PubMed

    Humphries, Murray M; McCann, Kevin S

    2014-01-01

    Ecological theory that is grounded in metabolic currencies and constraints offers the potential to link ecological outcomes to biophysical processes across multiple scales of organization. The metabolic theory of ecology (MTE) has emphasized the potential for metabolism to serve as a unified theory of ecology, while focusing primarily on the size and temperature dependence of whole-organism metabolic rates. Generalizing metabolic ecology requires extending beyond prediction and application of standardized metabolic rates to theory focused on how energy moves through ecological systems. A bibliometric and network analysis of recent metabolic ecology literature reveals a research network characterized by major clusters focused on MTE, foraging theory, bioenergetics, trophic status, and generalized patterns and predictions. This generalized research network, which we refer to as metabolic ecology, can be considered to include the scaling, temperature and stoichiometric models forming the core of MTE, as well as bioenergetic equations, foraging theory, life-history allocation models, consumer-resource equations, food web theory and energy-based macroecology models that are frequently employed in ecological literature. We conclude with six points we believe to be important to the advancement and integration of metabolic ecology, including nomination of a second fundamental equation, complementary to the first fundamental equation offered by the MTE. PMID:24028511

  10. Development and testing of a commercial scale coal-fired combustion system -- Phase 3. Final technical progress report, September 26, 1990--August 31, 1994

    SciTech Connect

    Litka, A.; Breault, R.

    1994-10-01

    This report summarizes the results of work performed in the development and testing of a coal-fired space heating system for the commercial market sector. Although coal is the most plentiful energy resource in the US, its use since World War II has been largely restricted to utility power generation for environmental and economic reasons. Within the commercial sector, oil and natural gas are the predominant heating fuels for office buildings, apartment complexes, and similar structures. Generally, these buildings require firing rates of 1 to 10 million Btu/hr. The objective of this program was to design, build, and test a coal-based heating system for this sector, and determine the economic viability and market potential for the system. Coal water slurry (CWS) fuel was chosen as the fuel form for this development effort. CWS eliminates the need to use dry pulverized coal with its attendant handling, metering, and dusting problems, as well as its explosive potential. A brief description of the overall system design is given in this report, as well as a discussion of the unique features of the system configuration and key components. This is followed by a summary of the testing performed, including a comparison between system performance and program goals. Finally, the results of the economic evaluation are presented, along with a commercialization plan for the technology. A key issue in the eventual commercialization of the technology is the availability of a competitively priced coal water slurry fuel. Predicted prices and availability of CWS are discussed.