BisGMA/TEGDMA dental nanocomposites containing glyoxylic acid modified high-aspect ratio hydroxyapatite nanofibers with enhanced dispersion

Science.gov (United States)

Chen, Liang; Xu, Changqi; Wang, Yong; Shi, Jian; Yu, Qingsong

2012-01-01

The purpose of this research was to investigate the influence of the glyoxylic acid (GA) modification of hydroxyapatite (HAP) nanofibers on their dispersion in bisphenol A glycidyl methacrylate (BisGMA)/triethylene glycol dimethacrylate (TEGDMA) dental composites and also investigate the mechanical properties, water absorption, and water solubility of the resulting dental resins and composites. Scanning/Transmission electron microscopy (STEM) images showed that microsized HAP nanofiber bundles could be effectively broken down to individual HAP nanofibers with an average length of ~15 μm after the surface modification process. Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) and thermal gravimetric analysis (TGA) characterization confirmed glyoxylic acid was chemically grafted on the HAP nanofiber surface, hypothetically by reacting with the amine group on HAP nanofiber surface. The enhanced dispersion of HAP nanofibers in dental matrix led to increased biaxial flexural strength (BFS) compared with the corresponding dental resins and composites filled with untreated HAP nanofibers. In addition, impregnation of small mass fractions of the glyoxylic acid modified HAP nanofibers into the BisGMA/TEGDMA dental resins (5wt%, 10wt%) or composites (2wt%, 3wt%) could also substantially improve the BFS in comparison with the controls(pure resins or dental composites filled with silica particles alone). Larger mass fractions could not further increase the mechanical property or even degrade the BFS values. Water behavior testing results indicated that the addition of glyoxylic acid modified HAP nanofibers resulted in higher water absorption and water solubility values which is not preferred for clinical application. In summary, well dispersed HAP nanofibers and their dental composites with enhanced mechanical property have been successfully fabricated but the water absorption and water solubility of such dental composites need to be

Liver peroxisomal alanine:glyoxylate aminotransferase and the effects of mutations associated with Primary Hyperoxaluria Type I: An overview.

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Oppici, Elisa; Montioli, Riccardo; Cellini, Barbara

2015-09-01

Liver peroxisomal alanine:glyoxylate aminotransferase (AGT) (EC 2.6.1.44) catalyses the conversion of l-alanine and glyoxylate to pyruvate and glycine, a reaction that allows glyoxylate detoxification. Inherited mutations on the AGXT gene encoding AGT lead to Primary Hyperoxaluria Type I (PH1), a rare disorder characterized by the deposition of calcium oxalate crystals primarily in the urinary tract. Here we describe the results obtained on the biochemical features of AGT as well as on the molecular and cellular effects of polymorphic and pathogenic mutations. A complex scenario on the molecular pathogenesis of PH1 emerges in which the co-inheritance of polymorphic changes and the condition of homozygosis or compound heterozygosis are two important factors that determine the enzymatic phenotype of PH1 patients. All the reported data represent relevant steps toward the understanding of genotype/phenotype correlations, the prediction of the response of the patients to the available therapies, and the development of new therapeutic approaches. This article is part of a Special Issue entitled: Cofactor-dependent proteins: evolution, chemical diversity and bio-applications. Copyright © 2015 Elsevier B.V. All rights reserved.

A kinetic study of the enhancement of solution chemiluminescence of glyoxylic acid oxidation by manganese species.

Science.gov (United States)

Otamonga, Jean-Paul; Abdel-Mageed, Amal; Agater, Irena B; Jewsbury, Roger A

2015-08-01

In order to study the mechanism of the enhancement of solution chemiluminescence, the kinetics of the decay of the oxidant and the chemiluminescence emission were followed for oxidations by permanganate, manganese dioxide sol and Mn(3+) (aq) of glyoxylic acid, using stopped-flow spectrophotometry. Results are reported for the glyoxylic acid oxidized under pseudo first-order conditions and in an acidic medium at 25 °C. For permanganate under these conditions, the decay is sigmoidal, consistent with autocatalysis, and for manganese dioxide sol and Mn(3+) it is pseudo first order. The effects of the presence of aqueous formaldehyde and Mn(2+) were observed and a fit to a simple mechanism is discussed. It is concluded that chemiluminescent enhancement in these systems is best explained by reaction kinetics. Copyright © 2014 John Wiley & Sons, Ltd.

Measuring cell cycle progression kinetics with metabolic labeling and flow cytometry.

Science.gov (United States)

Fleisig, Helen; Wong, Judy

2012-05-22

Precise control of the initiation and subsequent progression through the various phases of the cell cycle are of paramount importance in proliferating cells. Cell cycle division is an integral part of growth and reproduction and deregulation of key cell cycle components have been implicated in the precipitating events of carcinogenesis. Molecular agents in anti-cancer therapies frequently target biological pathways responsible for the regulation and coordination of cell cycle division. Although cell cycle kinetics tend to vary according to cell type, the distribution of cells amongst the four stages of the cell cycle is rather consistent within a particular cell line due to the consistent pattern of mitogen and growth factor expression. Genotoxic events and other cellular stressors can result in a temporary block of cell cycle progression, resulting in arrest or a temporary pause in a particular cell cycle phase to allow for instigation of the appropriate response mechanism. The ability to experimentally observe the behavior of a cell population with reference to their cell cycle progression stage is an important advance in cell biology. Common procedures such as mitotic shake off, differential centrifugation or flow cytometry-based sorting are used to isolate cells at specific stages of the cell cycle. These fractionated, cell cycle phase-enriched populations are then subjected to experimental treatments. Yield, purity and viability of the separated fractions can often be compromised using these physical separation methods. As well, the time lapse between separation of the cell populations and the start of experimental treatment, whereby the fractionated cells can progress from the selected cell cycle stage, can pose significant challenges in the successful implementation and interpretation of these experiments. Other approaches to study cell cycle stages include the use of chemicals to synchronize cells. Treatment of cells with chemical inhibitors of key

In vitro adsorption of oxalic acid and glyoxylic acid onto activated charcoal, resins and hydrous zirconium oxide

NARCIS (Netherlands)

Scholtens, R.; Scholten, J.; de Koning, H. W.; Tijssen, J.; ten Hoopen, H. W.; Olthuis, F. M.; Feijen, J.

1982-01-01

Patients suffering from primary hyperoxaluria show elevated plasma concentrations of oxalic acid and glyoxylic acid. The in vitro adsorption of these compounds into activated charcoal, a series of neutral and ion exchange resins and onto hydrous zirconium oxide has been investigated. Hydrous

Electrostatic interactions drive native-like aggregation of human alanine:glyoxylate aminostransferase.

Science.gov (United States)

Dindo, Mirco; Conter, Carolina; Cellini, Barbara

2017-11-01

Protein aggregate formation is the basis of several misfolding diseases, including those displaying loss-of-function pathogenesis. Although aggregation is often attributed to the population of intermediates exposing hydrophobic surfaces, the contribution of electrostatic forces has recently gained attention. Here, we combined computational and in vitro studies to investigate the aggregation process of human peroxisomal alanine:glyoxylate aminotransferase (AGT), a pyridoxal 5'-phosphate (PLP)-dependent enzyme involved in glyoxylate detoxification. We demonstrated that AGT is susceptible to electrostatic aggregation due to its peculiar surface charge anisotropy and that PLP binding counteracts the self-association process. The two polymorphic mutations P11L and I340M exert opposite effects. The P11L substitution enhances the aggregation tendency, probably by increasing surface charge anisotropy, while I340M plays a stabilizing role. In light of these results, we examined the effects of the most common missense mutations leading to primary hyperoxaluria type I (PH1), a rare genetic disorder associated with abnormal calcium oxalate precipitation in the urinary tract. All of them endow AGT with a strong electrostatic aggregation propensity. Moreover, we predicted that pathogenic mutations of surface residues could alter charge distribution, thus inducing aggregation under physiological conditions. A global model describing the AGT aggregation process is provided. Overall, the results indicate that the contribution of electrostatic interactions in determining the fate of proteins and the effect of amino acid substitutions should not be underestimated and provide the basis for the development of new therapeutic strategies for PH1 aimed at increasing AGT stability. © 2017 Federation of European Biochemical Societies.

Rho/ROCK signaling in regulation of corneal epithelial cell cycle progression.

Science.gov (United States)

Chen, Jian; Guerriero, Emily; Lathrop, Kira; SundarRaj, Nirmala

2008-01-01

The authors' previous study showed that the expression of a Rho-associated serine/threonine kinase (ROCK) is regulated during cell cycle progression in corneal epithelial cells. The present study was conducted to determine whether and how Rho/ROCK signaling regulates cell cycle progression. Rabbit corneal epithelial cells (RCECs) in culture were arrested in the G(0) phase of the cell cycle by serum deprivation and then allowed to re-enter the cell cycle in the presence or absence of the ROCK inhibitor (Y27632) in serum-supplemented medium. The number of cells in the S phase, the relative levels of specific cyclins and CDKs and their intracellular distribution, and the relative levels of mRNAs were determined by BrdU labeling, Western blot and immunocytochemical analyses, and real-time RT-PCR, respectively. ROCK inhibition delayed the progression of G(1) to S phase and led to a decrease in the number of RCECs entering the S phase between 12 and 24 hours from 31.5% +/- 4.5% to 8.1% +/- 2.6%. During the cell cycle progression, protein and mRNA levels of cyclin-D1 and -D3 and cyclin-dependent kinases CDK4 and CDK6 were significantly lower, whereas the protein levels of the CDK inhibitor p27(Kip1) were higher in ROCK-inhibited cells. Intracellular mRNA or protein levels of cyclin-E and protein levels of CDK2 were not significantly affected, but their nuclear translocation was delayed by ROCK inhibition. ROCK signaling is involved in cell cycle progression in RCECs, possibly by upregulation of cyclin-D1 and -D3 and CDK4, -6, and -2; nuclear translocation of CDK2 and cyclin-E; and downregulation of p27(Kip1).

Metabolic Engineering of TCA Cycle for Production of Chemicals.

Science.gov (United States)

Vuoristo, Kiira S; Mars, Astrid E; Sanders, Johan P M; Eggink, Gerrit; Weusthuis, Ruud A

2016-03-01

The tricarboxylic acid (TCA) cycle has been used for decades in the microbial production of chemicals such as citrate, L-glutamate, and succinate. Maximizing yield is key for cost-competitive production. However, for most TCA cycle products, the maximum pathway yield is lower than the theoretical maximum yield (Y(E)). For succinate, this was solved by creating two pathways to the product, using both branches of the TCA cycle, connected by the glyoxylate shunt (GS). A similar solution cannot be applied directly for production of compounds from the oxidative branch of the TCA cycle because irreversible reactions are involved. Here, we describe how this can be overcome and what the impact is on the yield. Copyright © 2015 Elsevier Ltd. All rights reserved.

Regulation of flux through metabolic cycles

International Nuclear Information System (INIS)

Walsh, K.

1984-01-01

The branchpoint of the tricarboxylic acid and glyoxylate shunt was characterized in the intact organism by a multidimensional approach. Theory and methodology were developed to determine velocities for the net flow of carbon through the major steps of acetate metabolism in E. coli. Rates were assigned based on the 13 C-NMR spectrum of intracellular glutamate, measured rates of substrate incorporation into end products, the constituent composition of E. coli and a series of conservation equations which described the system at steady state. The in vivo fluxes through the branchpoint of the tricarboxylic acid and glyoxylate cycles were compared to rates calculated from the kinetic constants of the branchpoint enzymes and the intracellular concentrations of their substrates. These studies elucidated the role of isocitrate dehydrogenase phosphorylation in the Krebs cycle and led to the development of a generalized mathematical description of the sensitivity of branchpoints to regulatory control. This theoretical analysis was termed the branchpoint effect and it describes conditions which result in large changes in the flux through an enzyme even though that enzyme is not subject to direct regulatory control. The theoretical and experimental characterization of this system provided a framework to study the effects of enzyme overproduction and underproduction on metabolic processes in the cell. An in vivo method was developed to determine the extent to which an enzyme catalyzes a rate-controlling reaction. The enzyme chosen for this study was citrate synthase

Allele-specific characterization of alanine: glyoxylate aminotransferase variants associated with primary hyperoxaluria.

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Melissa D Lage

Full Text Available Primary Hyperoxaluria Type 1 (PH1 is a rare autosomal recessive kidney stone disease caused by deficiency of the peroxisomal enzyme alanine: glyoxylate aminotransferase (AGT, which is involved in glyoxylate detoxification. Over 75 different missense mutations in AGT have been found associated with PH1. While some of the mutations have been found to affect enzyme activity, stability, and/or localization, approximately half of these mutations are completely uncharacterized. In this study, we sought to systematically characterize AGT missense mutations associated with PH1. To facilitate analysis, we used two high-throughput yeast-based assays: one that assesses AGT specific activity, and one that assesses protein stability. Approximately 30% of PH1-associated missense mutations are found in conjunction with a minor allele polymorphic variant, which can interact to elicit complex effects on protein stability and trafficking. To better understand this allele interaction, we functionally characterized each of 34 mutants on both the major (wild-type and minor allele backgrounds, identifying mutations that synergize with the minor allele. We classify these mutants into four distinct categories depending on activity/stability results in the different alleles. Twelve mutants were found to display reduced activity in combination with the minor allele, compared with the major allele background. When mapped on the AGT dimer structure, these mutants reveal localized regions of the protein that appear particularly sensitive to interactions with the minor allele variant. While the majority of the deleterious effects on activity in the minor allele can be attributed to synergistic interaction affecting protein stability, we identify one mutation, E274D, that appears to specifically affect activity when in combination with the minor allele.

Regulation of cell cycle progression by cell-cell and cell-matrix forces

NARCIS (Netherlands)

Uroz, Marina; Wistorf, Sabrina; Serra-Picamal, Xavier; Conte, Vito; Sales-Pardo, Marta; Roca-Cusachs, Pere; Guimerà, Roger; Trepat, Xavier

2018-01-01

It has long been proposed that the cell cycle is regulated by physical forces at the cell-cell and cell-extracellular matrix (ECM) interfaces 1-12 . However, the evolution of these forces during the cycle has never been measured in a tissue, and whether this evolution affects cell cycle progression

Cell cycle in egg cell and its progression during zygotic development in rice.

Science.gov (United States)

Sukawa, Yumiko; Okamoto, Takashi

2018-03-01

Rice egg is arrested at G1 phase probably by OsKRP2. After fusion with sperm, karyogamy, OsWEE1-mediated parental DNA integrity in zygote nucleus, zygote progresses cell cycle to produce two-celled embryo. In angiosperms, female and male gametes exist in gametophytes after the complementation of meiosis and the progression of nuclear/cell division of the haploid cell. Within the embryo sac, the egg cell is specially differentiated for fertilization and subsequent embryogenesis, and cellular programs for embryonic development, such as restarting the cell cycle and de novo gene expression, are halted. There is only limited knowledge about how the cell cycle in egg cells restarts toward zygotic division, although the conversion of the cell cycle from a quiescent and arrested state to an active state is the most evident transition of cell status from egg cell to zygote. This is partly due to the difficulty in direct access and analysis of egg cells, zygotes and early embryos, which are deeply embedded in ovaries. In this study, precise relative DNA amounts in the nuclei of egg cells, developing zygotes and cells of early embryos were measured, and the cell cycle of a rice egg cell was estimated as the G1 phase with a 1C DNA level. In addition, increases in DNA content in zygote nuclei via karyogamy and DNA replication were also detectable according to progression of the cell cycle. In addition, expression profiles for cell cycle-related genes in egg cells and zygotes were also addressed, and it was suggested that OsKRP2 and OsWEE1 function in the inhibition of cell cycle progression in egg cells and in checkpoint of parental DNA integrity in zygote nucleus, respectively.

Cell cycle progression in irradiated endothelial cells cultured from bovine aorta

International Nuclear Information System (INIS)

Rubin, D.B.; Drab, E.A.; Ward, W.F.; Bauer, K.D.

1988-01-01

Logarithmically growing endothelial cells from bovine aortas were exposed to single doses of 0-10 Gy of 60Co gamma rays, and cell cycle phase distribution and progression were examined by flow cytometry and autoradiography. In some experiments, cells were synchronized in the cell cycle with hydroxyurea (1 mM). Cell number in sham-irradiated control cultures doubled in approximately 24 h. Estimated cycle stage times for control cells were 14.4 h for G1 phase, 7.2 h for S phase, and 2.4 h for G2 + M phase. Irradiated cells demonstrated a reduced distribution at the G1/S phase border at 4 h, and an increased distribution in G2 + M phase at 24 h postirradiation. Autoradiographs of irradiated cells after continuous [3H]thymidine labeling indicated a block in G1 phase or at the G1/S-phase border. The duration of the block was dose dependent (2-3 min/cGy). Progression of the endothelial cells through S phase after removal of the hydroxyurea block also was retarded by irradiation, as demonstrated by increased distribution in early S phase and decreased distribution in late S phase. These results indicate that progression of asynchronous cultured bovine aortic endothelial cells through the DNA synthetic cycle is susceptible to radiation inhibition at specific sites in the cycle, resulting in redistribution and partial synchronization of the population. Thus aortic endothelial cells, diploid cells from a normal tissue, resemble many immortal cell types that have been examined in this regard in vitro

Progress and status of the Integral Fast Reactor (IFR) fuel cycle development

International Nuclear Information System (INIS)

Till, C.E.; Chang, Y.I.

1993-01-01

The Integral Fast Reactor (IFR) fuel cycle holds promise for substantial improvements in economics, diversion-resistance, and waste management. This paper discusses technical features of the IFR fuel cycle, its technical progress, the development status, and the future plans and directions

Progress and status of the Integral Fast Reactor (IFR) fuel cycle development

Energy Technology Data Exchange (ETDEWEB)

Till, C.E.; Chang, Y.I.

1993-03-01

The Integral Fast Reactor (IFR) fuel cycle holds promise for substantial improvements in economics, diversion-resistance, and waste management. This paper discusses technical features of the IFR fuel cycle, its technical progress, the development status, and the future plans and directions.

Progress and status of the Integral Fast Reactor (IFR) fuel cycle development

Energy Technology Data Exchange (ETDEWEB)

Till, C.E.; Chang, Y.I.

1993-01-01

The Integral Fast Reactor (IFR) fuel cycle holds promise for substantial improvements in economics, diversion-resistance, and waste management. This paper discusses technical features of the IFR fuel cycle, its technical progress, the development status, and the future plans and directions.

Progress and status of the Integral Fast Reactor (IFR) fuel cycle development

International Nuclear Information System (INIS)

Till, C.E.; Chang, Y.I.

1991-01-01

The Integral Fast Reactor (IFR) fuel cycle holds promise for substantial improvements in economics, diversion-resistance, and waste management. This paper discusses technical features of the IFR fuel cycle, its technical progress, the development status, and the future plans and directions. 10 refs

Progress and status of the Integral Fast Reactor (IFR) fuel cycle development

Energy Technology Data Exchange (ETDEWEB)

Till, C.E.; Chang, Y.I.

1991-01-01

The Integral Fast Reactor (IFR) fuel cycle holds promise for substantial improvements in economics, diversion-resistance, and waste management. This paper discusses technical features of the IFR fuel cycle, its technical progress, the development status, and the future plans and directions. 10 refs.

Progress and status of the Integral Fast Reactor (IFR) fuel cycle development

International Nuclear Information System (INIS)

Till, C.E.; Chang, Y.I.

1991-01-01

The Integral Fast Reactor (IFR) fuel cycle holds promise for substantial improvements in economics, diversion-resistance, and waste management. This paper discusses technical features of the IFR fuel cycle, its technical progress, the development status, and the future plans and directions. (author)

Lobaplatin arrests cell cycle progression in human hepatocellular carcinoma cells

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Chen Chang-Jie

2010-10-01

Full Text Available Abstract Background Hepatocellular carcinoma (HCC still is a big burden for China. In recent years, the third-generation platinum compounds have been proposed as potential active agents for HCC. However, more experimental and clinical data are warranted to support the proposal. In the present study, the effect of lobaplatin was assessed in five HCC cell lines and the underlying molecular mechanisms in terms of cell cycle kinetics were explored. Methods Cytotoxicity of lobaplatin to human HCC cell lines was examined using MTT cell proliferation assay. Cell cycle distribution was determined by flow cytometry. Expression of cell cycle-regulated genes was examined at both the mRNA (RT-PCR and protein (Western blot levels. The phosphorylation status of cyclin-dependent kinases (CDKs and retinoblastoma (Rb protein was also examined using Western blot analysis. Results Lobaplatin inhibited proliferation of human HCC cells in a dose-dependent manner. For the most sensitive SMMC-7721 cells, lobaplatin arrested cell cycle progression in G1 and G2/M phases time-dependently which might be associated with the down-regulation of cyclin B, CDK1, CDC25C, phosphorylated CDK1 (pCDK1, pCDK4, Rb, E2F, and pRb, and the up-regulation of p53, p21, and p27. Conclusion Cytotoxicity of lobaplatin in human HCC cells might be due to its ability to arrest cell cycle progression which would contribute to the potential use of lobaplatin for the management of HCC.

Catalytic asymmetric Meerwein-Ponndorf-Verley reduction of glyoxylates induced by a chiral N,N'-dioxide/Y(OTf)3 complex.

Science.gov (United States)

Wu, Wangbin; Zou, Sijia; Lin, Lili; Ji, Jie; Zhang, Yuheng; Ma, Baiwei; Liu, Xiaohua; Feng, Xiaoming

2017-03-18

An asymmetric Meerwein-Ponndorf-Verley (MPV) reduction of glyoxylates was for the first time accomplished via an N,N'-dioxide/Y(OTf) 3 complex with aluminium alkoxide and molecular sieves (MSs) as crucial additives. A variety of optically active α-hydroxyesters were obtained with excellent results. A possible reaction mechanism was proposed based on the experiments.

Application of high-performance liquid chromatography to the determination of glyoxylate synthesis in chick embryo liver.

Science.gov (United States)

Qureshi, A A; Elson, C E; Lebeck, L A

1982-11-19

The isolation and identification of three major alpha-keto end products (glyoxylate, pyruvate, alpha-ketoglutarate) of the isocitrate lyase reaction in 18-day chick embryo liver have been described. This was accomplished by the separation of these alpha-keto acids as their 2,4-dinitrophenylhydrazones (DNPHs) by high-performance liquid chromatography (HPLC). The DNPHs of alpha-keto acids were eluted with an isocratic solvent system of methanol-water-acetic acid (60:38.5:1.5) containing 5 mM tetrabutylammonium phosphate from a reversed-phase ultrasphere C18 (IP) and from a radial compression C18 column. The separation can be completed on the radial compression column within 15-20 min as compared to 30-40 min with a conventional reversed-phase column. Retention times and peak areas were integrated for both the assay samples and reference compounds. A relative measure of alpha-keto acid in the peak was calculated by comparison with the standard. The identification of each peak was done on the basis of retention time matching, co-chromatography with authentic compounds, and stopped flow UV-VIS scanning between 240 and 440 nm. Glyoxylate represented 5% of the total product of the isocitrate lyase reaction. Day 18 parallels the peak period of embryonic hepatic glycogenesis which occurs at a time when the original egg glucose reserve has been depleted.

A Dominant-Negative PPARγ Mutant Promotes Cell Cycle Progression and Cell Growth in Vascular Smooth Muscle Cells

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Joey Z. Liu

2009-01-01

Full Text Available PPARγ ligands have been shown to have antiproliferative effects on many cell types. We herein report that a synthetic dominant-negative (DN PPARγ mutant functions like a growth factor to promote cell cycle progression and cell proliferation in human coronary artery smooth muscle cells (CASMCs. In quiescent CASMCs, adenovirus-expressed DN-PPARγ promoted G1→S cell cycle progression, enhanced BrdU incorporation, and increased cell proliferation. DN-PPARγ expression also markedly enhanced positive regulators of the cell cycle, increasing Rb and CDC2 phosphorylation and the expression of cyclin A, B1, D1, and MCM7. Conversely, overexpression of wild-type (WT or constitutively-active (CA PPARγ inhibited cell cycle progression and the activity and expression of positive regulators of the cell cycle. DN-PPARγ expression, however, did not up-regulate positive cell cycle regulators in PPARγ-deficient cells, strongly suggesting that DN-PPARγ effects on cell cycle result from blocking the function of endogenous wild-type PPARγ. DN-PPARγ expression enhanced phosphorylation of ERK MAPKs. Furthermore, the ERK specific-inhibitor PD98059 blocked DN-PPARγ-induced phosphorylation of Rb and expression of cyclin A and MCM7. Our data thus suggest that DN-PPARγ promotes cell cycle progression and cell growth in CASMCs by modulating fundamental cell cycle regulatory proteins and MAPK mitogenic signaling pathways in vascular smooth muscle cells (VSMCs.

Certain and progressive methylation of histone H4 at lysine 20 during the cell cycle.

Science.gov (United States)

Pesavento, James J; Yang, Hongbo; Kelleher, Neil L; Mizzen, Craig A

2008-01-01

Methylation of histone H4 at lysine 20 (K20) has been implicated in transcriptional activation, gene silencing, heterochromatin formation, mitosis, and DNA repair. However, little is known about how this modification is regulated or how it contributes to these diverse processes. Metabolic labeling and top-down mass spectrometry reveal that newly synthesized H4 is progressively methylated at K20 during the G(2), M, and G(1) phases of the cell cycle in a process that is largely inescapable and irreversible. Approximately 98% of new H4 becomes dimethylated within two to three cell cycles, and K20 methylation turnover in vivo is undetectable. New H4 is methylated regardless of prior acetylation, and acetylation occurs predominantly on K20-dimethylated H4, refuting the hypothesis that K20 methylation antagonizes H4 acetylation and represses transcription epigenetically. Despite suggestions that it is required for normal mitosis and cell cycle progression, K20 methylation proceeds normally during colchicine treatment. Moreover, delays in PR-Set7 synthesis and K20 methylation which accompany altered cell cycle progression during sodium butyrate treatment appear to be secondary to histone hyperacetylation or other effects of butyrate since depletion of PR-Set7 did not affect cell cycle progression. Together, our data provide an unbiased perspective of the regulation and function of K20 methylation.

Establishment of human papillomavirus infection requires cell cycle progression.

Directory of Open Access Journals (Sweden)

Dohun Pyeon

2009-02-01

Full Text Available Human papillomaviruses (HPVs are DNA viruses associated with major human cancers. As such there is a strong interest in developing new means, such as vaccines and microbicides, to prevent HPV infections. Developing the latter requires a better understanding of the infectious life cycle of HPVs. The HPV infectious life cycle is closely linked to the differentiation state of the stratified epithelium it infects, with progeny virus only made in the terminally differentiating suprabasal compartment. It has long been recognized that HPV must first establish its infection within the basal layer of stratified epithelium, but why this is the case has not been understood. In part this restriction might reflect specificity of expression of entry receptors. However, this hypothesis could not fully explain the differentiation restriction of HPV infection, since many cell types can be infected with HPVs in monolayer cell culture. Here, we used chemical biology approaches to reveal that cell cycle progression through mitosis is critical for HPV infection. Using infectious HPV16 particles containing the intact viral genome, G1-synchronized human keratinocytes as hosts, and early viral gene expression as a readout for infection, we learned that the recipient cell must enter M phase (mitosis for HPV infection to take place. Late M phase inhibitors had no effect on infection, whereas G1, S, G2, and early M phase cell cycle inhibitors efficiently prevented infection. We conclude that host cells need to pass through early prophase for successful onset of transcription of the HPV encapsidated genes. These findings provide one reason why HPVs initially establish infections in the basal compartment of stratified epithelia. Only this compartment of the epithelium contains cells progressing through the cell cycle, and therefore it is only in these cells that HPVs can establish their infection. By defining a major condition for cell susceptibility to HPV infection, these

Certain amplified genomic-DNA fragments (AGFs) may be involved in cell cycle progression and chloroquine is found to induce the production of cell-cycle-associated AGFs (CAGFs) in Plasmodium falciparum

OpenAIRE

Li, Gao-De

2015-01-01

It is well known that cyclins are a family of proteins that control cell-cycle progression by activating cyclin-dependent kinase. Based on our experimental results, we propose here a novel hypothesis that certain amplified genomic-DNA fragments (AGFs) may also be required for the cell cycle progression of eukaryotic cells and thus can be named as cell-cycle-associated AGFs (CAGFs). Like fluctuation in cyclin levels during cell cycle progression, these CAGFs are amplified and degraded at diffe...

Progress in Finite Time Thermodynamic Studies for Internal Combustion Engine Cycles

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Yanlin Ge

2016-04-01

Full Text Available On the basis of introducing the origin and development of finite time thermodynamics (FTT, this paper reviews the progress in FTT optimization for internal combustion engine (ICE cycles from the following four aspects: the studies on the optimum performances of air standard endoreversible (with only the irreversibility of heat resistance and irreversible ICE cycles, including Otto, Diesel, Atkinson, Brayton, Dual, Miller, Porous Medium and Universal cycles with constant specific heats, variable specific heats, and variable specific ratio of the conventional and quantum working fluids (WFs; the studies on the optimum piston motion (OPM trajectories of ICE cycles, including Otto and Diesel cycles with Newtonian and other heat transfer laws; the studies on the performance limits of ICE cycles with non-uniform WF with Newtonian and other heat transfer laws; as well as the studies on the performance simulation of ICE cycles. In the studies, the optimization objectives include work, power, power density, efficiency, entropy generation rate, ecological function, and so on. The further direction for the studies is explored.

Characterization of recombinant glyoxylate reductase from thermophile Thermus thermophilus HB27.

Science.gov (United States)

Ogino, Hiroyasu; Nakayama, Hitoshi; China, Hideyasu; Kawata, Takuya; Doukyu, Noriyuki; Yasuda, Masahiro

2008-01-01

A glyoxylate reductase gene from the thermophilic bacterium Thermus thermophilus HB27 (TthGR) was cloned and expressed in Escherichia coli cells. The recombinant enzyme was highly purified to homogeneity and characterized. The purified TthGR showed thermostability up to 70 degrees C. In contrast, the maximum reaction condition was relatively mild (45 degrees C and pH 6.7). Although the kcat values against co-enzyme NADH and NADPH were similar, the Km value against co-enzyme NADH was approximately 18 times higher than that against NADPH. TthGR prefers NADPH rather than NADH as an electron donor. These results indicate that a phosphate group of a co-enzyme affects the binding affinity rather than the reaction efficiency, and TthGR demands appropriate amount of phosphate for a high activity. Furthermore, it was found that the half-lives of TthGR in the presence of 25% dimethyl sulfoxide and diethylene glycol were significantly longer than that in the absence of an organic solvent.

Soaking RNAi in Bombyx mori BmN4-SID1 Cells Arrests Cell Cycle Progression

Science.gov (United States)

Mon, Hiroaki; Li, Zhiqing; Kobayashi, Isao; Tomita, Shuichiro; Lee, JaeMan; Sezutsu, Hideki; Tamura, Toshiki; Kusakabe, Takahiro

2013-01-01

RNA interference (RNAi) is an evolutionarily conserved mechanism for sequence-specific gene silencing. Previously, the BmN4-SID1 cell expressing Caenorhabditis ele gans SID-1 was established, in which soaking RNAi could induce effective gene silencing. To establish its utility, 6 cell cycle progression related cDNAs, CDK1, MYC, MYB, RNRS, CDT1, and GEMININ, were isolated from the silkworm, Bombyx mori L. (Lepidoptera: Bombycidae), and their expressions were further silenced by soaking RNAi in the BmN4-SID1 cells. The cell cycle progression analysis using flow cytometer demonstrated that the small amount of double stranded RNA was enough to arrest cell cycle progression at the specific cell phases. These data suggest that RNAi in the BmN4-SID1 cells can be used as a powerful tool for loss-of-function analysis of B. mori genes. PMID:24773378

Nuclear receptor TLX regulates cell cycle progression in neural stem cells of the developing brain.

Science.gov (United States)

Li, Wenwu; Sun, Guoqiang; Yang, Su; Qu, Qiuhao; Nakashima, Kinichi; Shi, Yanhong

2008-01-01

TLX is an orphan nuclear receptor that is expressed exclusively in vertebrate forebrains. Although TLX is known to be expressed in embryonic brains, the mechanism by which it influences neural development remains largely unknown. We show here that TLX is expressed specifically in periventricular neural stem cells in embryonic brains. Significant thinning of neocortex was observed in embryonic d 14.5 TLX-null brains with reduced nestin labeling and decreased cell proliferation in the germinal zone. Cell cycle analysis revealed both prolonged cell cycles and increased cell cycle exit in TLX-null embryonic brains. Increased expression of a cyclin-dependent kinase inhibitor p21 and decreased expression of cyclin D1 provide a molecular basis for the deficiency of cell cycle progression in embryonic brains of TLX-null mice. Furthermore, transient knockdown of TLX by in utero electroporation led to precocious cell cycle exit and differentiation of neural stem cells followed by outward migration. Together these results indicate that TLX plays an important role in neural development by regulating cell cycle progression and exit of neural stem cells in the developing brain.

Progress on Variable Cycle Engines

Science.gov (United States)

Westmoreland, J. S.; Howlett, R. A.; Lohmann, R. P.

1979-01-01

Progress in the development and future requirements of the Variable Stream Control Engine (VSCE) are presented. The two most critical components of this advanced system for future supersonic transports, the high performance duct burner for thrust augmentation, and the low jet coannular nozzle were studied. Nozzle model tests substantiated the jet noise benefit associated with the unique velocity profile possible with a coannular nozzle system on a VSCE. Additional nozzle model performance tests have established high thrust efficiency levels only at takeoff and supersonic cruise for this nozzle system. An experimental program involving both isolated component and complete engine tests has been conducted for the high performance, low emissions duct burner with good results and large scale testing of these two components is being conducted using a F100 engine as the testbed for simulating the VSCE. Future work includes application of computer programs for supersonic flow fields to coannular nozzle geometries, further experimental testing with the duct burner segment rig, and the use of the Variable Cycle Engine (VCE) Testbed Program for evaluating the VSCE duct burner and coannular nozzle technologies.

Morphogenesis checkpoint kinase Swe1 is the executor of lipolysis-dependent cell-cycle progression.

Science.gov (United States)

Chauhan, Neha; Visram, Myriam; Cristobal-Sarramian, Alvaro; Sarkleti, Florian; Kohlwein, Sepp D

2015-03-10

Cell growth and division requires the precise duplication of cellular DNA content but also of membranes and organelles. Knowledge about the cell-cycle-dependent regulation of membrane and storage lipid homeostasis is only rudimentary. Previous work from our laboratory has shown that the breakdown of triacylglycerols (TGs) is regulated in a cell-cycle-dependent manner, by activation of the Tgl4 lipase by the major cyclin-dependent kinase Cdc28. The lipases Tgl3 and Tgl4 are required for efficient cell-cycle progression during the G1/S (Gap1/replication phase) transition, at the onset of bud formation, and their absence leads to a cell-cycle delay. We now show that defective lipolysis activates the Swe1 morphogenesis checkpoint kinase that halts cell-cycle progression by phosphorylation of Cdc28 at tyrosine residue 19. Saturated long-chain fatty acids and phytosphingosine supplementation rescue the cell-cycle delay in the Tgl3/Tgl4 lipase-deficient strain, suggesting that Swe1 activity responds to imbalanced sphingolipid metabolism, in the absence of TG degradation. We propose a model by which TG-derived sphingolipids are required to activate the protein phosphatase 2A (PP2A(Cdc55)) to attenuate Swe1 phosphorylation and its inhibitory effect on Cdc28 at the G1/S transition of the cell cycle.

Chloroplast Dysfunction Causes Multiple Defects in Cell Cycle Progression in the Arabidopsis crumpled leaf Mutant

KAUST Repository

Hudik, Elodie

2014-07-18

The majority of research on cell cycle regulation is focused on the nuclear events that govern the replication and segregation of the genome between the two daughter cells. However, eukaryotic cells contain several compartmentalized organelles with specialized functions, and coordination among these organelles is required for proper cell cycle progression, as evidenced by the isolation of several mutants in which both organelle function and overall plant development were affected. To investigate how chloroplast dysfunction affects the cell cycle, we analyzed the crumpled leaf (crl) mutant of Arabidopsis (Arabidopsis thaliana), which is deficient for a chloroplastic protein and displays particularly severe developmental defects. In the crl mutant, we reveal that cell cycle regulation is altered drastically and that meristematic cells prematurely enter differentiation, leading to reduced plant stature and early endoreduplication in the leaves. This response is due to the repression of several key cell cycle regulators as well as constitutive activation of stress-response genes, among them the cell cycle inhibitor SIAMESE-RELATED5. One unique feature of the crl mutant is that it produces aplastidic cells in several organs, including the root tip. By investigating the consequence of the absence of plastids on cell cycle progression, we showed that nuclear DNA replication occurs in aplastidic cells in the root tip, which opens future research prospects regarding the dialogue between plastids and the nucleus during cell cycle regulation in higher plants.

Rho-associated kinase (ROCK) function is essential for cell cycle progression, senescence and tumorigenesis.

Science.gov (United States)

Kümper, Sandra; Mardakheh, Faraz K; McCarthy, Afshan; Yeo, Maggie; Stamp, Gordon W; Paul, Angela; Worboys, Jonathan; Sadok, Amine; Jørgensen, Claus; Guichard, Sabrina; Marshall, Christopher J

2016-01-14

Rho-associated kinases 1 and 2 (ROCK1/2) are Rho-GTPase effectors that control key aspects of the actin cytoskeleton, but their role in proliferation and cancer initiation or progression is not known. Here, we provide evidence that ROCK1 and ROCK2 act redundantly to maintain actomyosin contractility and cell proliferation and that their loss leads to cell-cycle arrest and cellular senescence. This phenotype arises from down-regulation of the essential cell-cycle proteins CyclinA, CKS1 and CDK1. Accordingly, while the loss of either Rock1 or Rock2 had no negative impact on tumorigenesis in mouse models of non-small cell lung cancer and melanoma, loss of both blocked tumor formation, as no tumors arise in which both Rock1 and Rock2 have been genetically deleted. Our results reveal an indispensable role for ROCK, yet redundant role for isoforms 1 and 2, in cell cycle progression and tumorigenesis, possibly through the maintenance of cellular contractility.

The human RNA polymerase II-associated factor 1 (hPaf1: a new regulator of cell-cycle progression.

Directory of Open Access Journals (Sweden)

Nicolas Moniaux

2009-09-01

Full Text Available The human PAF (hPAF complex is part of the RNA polymerase II transcription apparatus and regulates multiple steps in gene expression. Further, the yeast homolog of hPaf1 has a role in regulating the expression of a subset of genes involved in the cell-cycle. We therefore investigated the role of hPaf1 during progression of the cell-cycle.Herein, we report that the expression of hPaf1, a subunit of the hPAF complex, increases with cell-cycle progression and is regulated in a cell-cycle dependant manner. hPaf1 specifically regulates a subclass of genes directly implicated in cell-cycle progression during G1/S, S/G2, and G2/M. In prophase, hPaf1 aligns in filament-like structures, whereas in metaphase it is present within the pole forming a crown-like structure, surrounding the centrosomes. Moreover, hPaf1 is degraded during the metaphase to anaphase transition. In the nucleus, hPaf1 regulates the expression of cyclins A1, A2, D1, E1, B1, and Cdk1. In addition, expression of hPaf1 delays DNA replication but favors the G2/M transition, in part through microtubule assembly and mitotic spindle formation.Our results identify hPaf1 and the hPAF complex as key regulators of cell-cycle progression. Mutation or loss of stoichiometry of at least one of the members may potentially lead to cancer development.

The Aspergillus nidulans acuL gene encodes a mitochondrial carrier required for the utilization of carbon sources that are metabolized via the TCA cycle.

Science.gov (United States)

Flipphi, Michel; Oestreicher, Nathalie; Nicolas, Valérie; Guitton, Audrey; Vélot, Christian

2014-07-01

In Aspergillus nidulans, the utilization of acetate as sole carbon source requires several genes (acu). Most of them are also required for the utilization of fatty acids. This is the case for acuD and acuE, which encode the two glyoxylate cycle-specific enzymes, isocitrate lyase and malate synthase, respectively, but also for acuL that we have identified as AN7287, and characterized in this study. Deletion of acuL resulted in the same phenotype as the original acuL217 mutant. acuL encodes a 322-amino acid protein which displays all the structural features of a mitochondrial membrane carrier, and shares 60% identity with the Saccharomyces cerevisiae succinate/fumarate mitochondrial antiporter Sfc1p (also named Acr1p). Consistently, the AcuL protein was shown to localize in mitochondria, and partial cross-complementation was observed between the S. cerevisiae and A. nidulans homologues. Extensive phenotypic characterization suggested that the acuL gene is involved in the utilization of carbon sources that are catabolized via the TCA cycle, and therefore require gluconeogenesis. In addition, acuL proves to be co-regulated with acuD and acuE. Overall, our data suggest that AcuL could link the glyoxylate cycle to gluconeogenesis by exchanging cytoplasmic succinate for mitochondrial fumarate. Copyright © 2014 Elsevier Inc. All rights reserved.

MMSET is dynamically regulated during cell-cycle progression and promotes normal DNA replication.

Science.gov (United States)

Evans, Debra L; Zhang, Haoxing; Ham, Hyoungjun; Pei, Huadong; Lee, SeungBaek; Kim, JungJin; Billadeau, Daniel D; Lou, Zhenkun

2016-01-01

The timely and precise duplication of cellular DNA is essential for maintaining genome integrity and is thus tightly-regulated. During mitosis and G1, the Origin Recognition Complex (ORC) binds to future replication origins, coordinating with multiple factors to load the minichromosome maintenance (MCM) complex onto future replication origins as part of the pre-replication complex (pre-RC). The pre-RC machinery, in turn, remains inactive until the subsequent S phase when it is required for replication fork formation, thereby initiating DNA replication. Multiple myeloma SET domain-containing protein (MMSET, a.k.a. WHSC1, NSD2) is a histone methyltransferase that is frequently overexpressed in aggressive cancers and is essential for normal human development. Several studies have suggested a role for MMSET in cell-cycle regulation; however, whether MMSET is itself regulated during cell-cycle progression has not been examined. In this study, we report that MMSET is degraded during S phase in a cullin-ring ligase 4-Cdt2 (CRL4(Cdt2)) and proteasome-dependent manner. Notably, we also report defects in DNA replication and a decreased association of pre-RC factors with chromatin in MMSET-depleted cells. Taken together, our results suggest a dynamic regulation of MMSET levels throughout the cell cycle, and further characterize the role of MMSET in DNA replication and cell-cycle progression.

Uncovering SUMOylation Dynamics during Cell-Cycle Progression Reveals FoxM1 as a Key Mitotic SUMO Target Protein

DEFF Research Database (Denmark)

Schimmel, Joost; Eifler, Karolin; Sigurdsson, Jón Otti

2014-01-01

Loss of small ubiquitin-like modification (SUMOylation) in mice causes genomic instability due to the missegregation of chromosomes. Currently, little is known about the identity of relevant SUMO target proteins that are involved in this process and about global SUMOylation dynamics during cell......-cycle progression. We performed a large-scale quantitative proteomics screen to address this and identified 593 proteins to be SUMO-2 modified, including the Forkhead box transcription factor M1 (FoxM1), a key regulator of cell-cycle progression and chromosome segregation. SUMOylation of FoxM1 peaks during G2 and M...... relieving FoxM1 autorepression. Cells deficient for FoxM1 SUMOylation showed increased levels of polyploidy. Our findings contribute to understanding the role of SUMOylation during cell-cycle progression....

Plant hormone cytokinins control cell cycle progression and plastid replication in apicomplexan parasites.

Science.gov (United States)

Andrabi, Syed Bilal Ahmad; Tahara, Michiru; Matsubara, Ryuma; Toyama, Tomoko; Aonuma, Hiroka; Sakakibara, Hitoshi; Suematsu, Makoto; Tanabe, Kazuyuki; Nozaki, Tomoyoshi; Nagamune, Kisaburo

2018-02-01

Cytokinins are plant hormones that are involved in regulation of cell proliferation, cell cycle progression, and cell and plastid development. Here, we show that the apicomplexan parasites Toxoplasma gondii and Plasmodium berghei, an opportunistic human pathogen and a rodent malaria agent, respectively, produce cytokinins via a biosynthetic pathway similar to that in plants. Cytokinins regulate the growth and cell cycle progression of T. gondii by mediating expression of the cyclin gene TgCYC4. A natural form of cytokinin, trans-zeatin (t-zeatin), upregulated expression of this cyclin, while a synthetic cytokinin, thidiazuron, downregulated its expression. Immunofluorescence microscopy and quantitative PCR analysis showed that t-zeatin increased the genome-copy number of apicoplast, which are non-photosynthetic plastid, in the parasite, while thidiazuron led to their disappearance. Thidiazuron inhibited growth of T. gondii and Plasmodium falciparum, a human malaria parasite, suggesting that thidiazuron has therapeutic potential as an inhibitor of apicomplexan parasites. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Macrophage/epithelium cross-talk regulates cell cycle progression and migration in pancreatic progenitors.

Directory of Open Access Journals (Sweden)

Kristin Mussar

Full Text Available Macrophages populate the mesenchymal compartment of all organs during embryogenesis and have been shown to support tissue organogenesis and regeneration by regulating remodeling of the extracellular microenvironment. Whether this mesenchymal component can also dictate select developmental decisions in epithelia is unknown. Here, using the embryonic pancreatic epithelium as model system, we show that macrophages drive the epithelium to execute two developmentally important choices, i.e. the exit from cell cycle and the acquisition of a migratory phenotype. We demonstrate that these developmental decisions are effectively imparted by macrophages activated toward an M2 fetal-like functional state, and involve modulation of the adhesion receptor NCAM and an uncommon "paired-less" isoform of the transcription factor PAX6 in the epithelium. Over-expression of this PAX6 variant in pancreatic epithelia controls both cell motility and cell cycle progression in a gene-dosage dependent fashion. Importantly, induction of these phenotypes in embryonic pancreatic transplants by M2 macrophages in vivo is associated with an increased frequency of endocrine-committed cells emerging from ductal progenitor pools. These results identify M2 macrophages as key effectors capable of coordinating epithelial cell cycle withdrawal and cell migration, two events critical to pancreatic progenitors' delamination and progression toward their differentiated fates.

Macrophage/epithelium cross-talk regulates cell cycle progression and migration in pancreatic progenitors.

Science.gov (United States)

Mussar, Kristin; Tucker, Andrew; McLennan, Linsey; Gearhart, Addie; Jimenez-Caliani, Antonio J; Cirulli, Vincenzo; Crisa, Laura

2014-01-01

Macrophages populate the mesenchymal compartment of all organs during embryogenesis and have been shown to support tissue organogenesis and regeneration by regulating remodeling of the extracellular microenvironment. Whether this mesenchymal component can also dictate select developmental decisions in epithelia is unknown. Here, using the embryonic pancreatic epithelium as model system, we show that macrophages drive the epithelium to execute two developmentally important choices, i.e. the exit from cell cycle and the acquisition of a migratory phenotype. We demonstrate that these developmental decisions are effectively imparted by macrophages activated toward an M2 fetal-like functional state, and involve modulation of the adhesion receptor NCAM and an uncommon "paired-less" isoform of the transcription factor PAX6 in the epithelium. Over-expression of this PAX6 variant in pancreatic epithelia controls both cell motility and cell cycle progression in a gene-dosage dependent fashion. Importantly, induction of these phenotypes in embryonic pancreatic transplants by M2 macrophages in vivo is associated with an increased frequency of endocrine-committed cells emerging from ductal progenitor pools. These results identify M2 macrophages as key effectors capable of coordinating epithelial cell cycle withdrawal and cell migration, two events critical to pancreatic progenitors' delamination and progression toward their differentiated fates.

Progress and status of the integral fast reactor (IFR) fuel cycle development

International Nuclear Information System (INIS)

Till, C.E.; Chang, Y.I.

1993-01-01

The Integral Fast Reactor (IFR) fuel cycle holds promise for substantial improvements in economics, diversion-resistance, and waste management. This paper discusses technical features of the IFR fuel cycle, its technical progress, the development status, and the future plans and directions. The Integral Fast Reactor (IFR) fuel cycle, is based on the use of a metallic fuel alloy (U-Pu-Zr) that permits use of an innovative method for processing of spent fuel. This method, a combination of pyrometallurgical and electrochemical processes, has been termed pyroprocessing. It offers the advantages of a simple, compact processing system and limited volumes of stabilized high-level wastes. This translates to an economically viable system that is likely to receive favorable public response, particularly when combined with the other attributes of the Integral Fast Reactor. Substantial progress has been made in the development of the IFR pyroprocessing method. A comprehensive demonstration of the process will soon begin at the Argonne National Laboratory Idaho site, using spent fuel from the EBR-II reactor. An important advantage of the IFR is its ability to recycle fuel in the process of power generation, extending fuel resources by a considerable amount and assuring the continued viability of nuclear power stations by reducing dependence on external fuel supplies. Pyroprocessing is the means whereby the recycle process is accomplished. It can also be applied to the recovery of fuel constituents from spent fuel generated in the process of operation of conventional light water reactor power plants, offering the means to recover the valuable fuel resources remaining in that material

Research progress of socio-economic water cycle in China

Institute of Scientific and Technical Information of China (English)

无

2002-01-01

China has made great progress in the study of socio-economic water cycle. She has completed national water resources appraisement and medium to long-term water supply planning. She has been engaging in study on water-deficient regions in North China and Northwest China for about half a century. For solving water shortage problem in northern China, she has put forward the famous South-to-North Water Transferring Projects, which has been set as one of the four biggest national projects in the Tenth Five-Year-Plan period although there are still debates. For promoting water use efficiency, China has been reforming her water management system, including water right system and water price system. There has already been a case of water right purchase. China has also done a lot of research on the interaction between human activity, water and ecosystem. For meeting the need of sustainability and coordinating water resources development and environmental protection, the study of ecological water requirement became very hot in recent years. There are three focuses of socio-economic water cycle study now in China: water transfer projects from the south to the north, water resources management and ecological water requirement.

The regulation effect of STAT 5 signaling pathway on the cell cycle progression of irradiated KG-1 cells

International Nuclear Information System (INIS)

Guo Dehuang; Dong Bo; Luo Qingliang; Wen Gengyun; Mao Bingzhi

2000-01-01

The author investigated the role of the JAK/STAT signaling pathway regulating cell cycle progression in the irradiated KG-1 cells. By permanent transfecting the cells with DN-STAT 5 cDNA to block the JAK/STAT signaling pathway and then transient transfecting with cyclin D 1 or cyclin B 1 cDNA, the effects of cyclin D 1 protein and cyclin B 1 protein on the cell cycle progression were examined. Results showed that after irradiation with 8Gy 60 Co rays, the irradiated KG-1 cells transfected with only DN-STAT 5 cDNA can not recover form the G 1 arrest, even though GM-CSF was added. Meanwhile, the cells transfected with both the DN-STAT 5 cDNA and cyclin D 1 cDNA or cyclin B 1 cDNA can recover from the G 1 arrest or the G 2 arrest to a great extent. Thus, it was proved indirectly that the JAK/STAT signaling pathway activated by GM-CSF regulated the cell cycle progression through cyclin D 1 and cyclin B 1 protein

Extracellular matrix-dependent myosin dynamics during G1-S phase cell cycle progression in hepatocytes

International Nuclear Information System (INIS)

Bhadriraju, Kiran; Hansen, Linda K.

2004-01-01

Cell spreading and proliferation are tightly coupled in anchorage-dependent cells. While adhesion-dependent proliferation signals require an intact actin cytoskeleton, and some of these signals such as ERK activation have been characterized, the role of myosin in spreading and cell cycle progression under different extracellular matrix (ECM) conditions is not known. Studies presented here examine changes in myosin activity in freshly isolated hepatocytes under ECM conditions that promote either proliferation (high fibronectin density) or growth arrest (low fibronectin density). Three different measures were obtained and related to both spreading and cell cycle progression: myosin protein levels and association with cytoskeleton, myosin light chain phosphorylation, and its ATPase activity. During the first 48 h in culture, corresponding with transit through G1 phase, there was a six-fold increase in both myosin protein levels and myosin association with actin cytoskeleton. There was also a steady increase in myosin light chain phosphorylation and ATPase activity with spreading, which did not occur in non-spread, growth-arrested cells on low density of fibronectin. Myosin-inhibiting drugs blocked ERK activation, cyclin D1 expression, and S phase entry. Overexpression of the cell cycle protein cyclin D1 overcame both ECM-dependent and actomyosin-dependent inhibition of DNA synthesis, suggesting that cyclin D1 is a key event downstream of myosin-dependent cell cycle regulation

Function of trehalose and glycogen in cell cycle progression and cell viability in Saccharomyces cerevisiae

NARCIS (Netherlands)

Silljé, H H; Paalman, J W; ter Schure, E G; Olsthoorn, S Q; Verkleij, A J; Boonstra, Johannes; Verrips, C T

Trehalose and glycogen accumulate in Saccharomyces cerevisiae when growth conditions deteriorate. It has been suggested that aside from functioning as storage factors and stress protectants, these carbohydrates may be required for cell cycle progression at low growth rates under carbon limitation.

Effects of [3H]UdR on the cell-cycle progression of L1210 cells

International Nuclear Information System (INIS)

Darzynkiewicz, Z.; Carter, S.; Kimmel, M.

1984-01-01

Tritium-labelled uridine (( 3 H)UdR)perturbs progression of L1210 cells through the mitotic cycle. A slowdown of G 2 cells is observed 2 hr after addition of 0.5-5.0 μci/ml of ( 3 H)UdR into cultures. At 2.5-5.0 μCi/ml of ( 3 H)UdR a slowdown of cell progression through S is also apparent. Additionally, there is an increase in the number of cells with DNA values higher than 4C in cultures growing in the presence of ( 3 H)UdR for 8-24 hr. A pulse of ( 3 H)UdR of 2 hr duration labels predominantly (95%) cellular RNA. The first cell-cycle effects (G 2 slowdown) are observed when the amount of the incorporated ( 3 H)UdR is such that, on average there are fewer than thirty-six ( 3 H) decays per cell which corresponds to approximately 12-19 rads. The S-phase slowdown is seen at a dose of incorporated ( 3 H)UdR twice as high as that inducing G 2 effects. The specific localization of ( 3 H)UdR in nucleoli, peripheral nucleoplasm and in cytoplasm, as well as differences in the kinetics of the incorporation in relation to phases of the cell cycle are discussed. Mathematical modelling of the cell-cycle effects of ( 3 H)UdR is provided. (author)

The progressive achievement of a closed fuel cycle in France; La mise en oeuvre progressive d'un cycle ferme en France

Energy Technology Data Exchange (ETDEWEB)

Hugelmann, D.; Devezeaux de Lavergne, J.G. [AREVA NC, 78 - Velizy Villacoublay (France)

2008-03-15

The author reviews the progressive building of a strong nuclear fuel cycle industry in France. The first major step was the abandon of the graphite-gas reactor system to the PWR system. The government's decision to opt for reactors operating with enriched uranium opened the way to the application at an industrial scale of uranium enrichment technology that was only confined to military purposes. The legal entity 'EURODIF S A' was founded at that time and the different production units of the George-Besse-1 enrichment plant entered into service progressively from 1978 to 1982. The Comurhex company was created in 1969, and was in charge of producing the uranium hexafluoride necessary to the fabrication of nuclear fuels. La-Hague plant entered into service in 1966, its aim was to process spent fuels from graphite-gas reactors. Inside this plant the HAO (High Activity Oxide) dedicated to PWR spent fuels was operating in 1974. The MELOX plant dedicated to the fabrication of mixed oxides fuels (Mox) entered into operation in 1995 (till now more than 5000 Mox assemblies have been fabricated. Another important step was the processing of Mox fuels. During these 30 years, the nuclear industry has made impressing progress concerning: the increase of burn-up rates, the performance of fuels, the increase in the volume being processed, the packaging of radioactive wastes, the development of nuclear transport, and a reduction of the impact on the environment. In order to maintain its level of performance the nuclear industry has made important investments concerning: mining (a global investment of 2.3*10{sup 9} euros), Comurhex-2 (a 610*10{sup 6} euros investment) and Georges-Besse-2 plant (a 3*10{sup 9} euros investment for the enrichment of uranium through centrifugation). (A.C.)

An Exercise Model to Study Progressive Muscle Fatigue During Constant Work Rate Exercise on a Cycle Ergometer

National Research Council Canada - National Science Library

Fulco, Charles

2003-01-01

... of the same muscles during the activity. However, conventional ergometric testing modes such as stationary cycling or treadmill exercise do not readily lend themselves to quantitating the progressive increase in muscle fatigue...

Idas, a Novel Phylogenetically Conserved Geminin-related Protein, Binds to Geminin and Is Required for Cell Cycle Progression*

Science.gov (United States)

Pefani, Dafni-Eleutheria; Dimaki, Maria; Spella, Magda; Karantzelis, Nickolas; Mitsiki, Eirini; Kyrousi, Christina; Symeonidou, Ioanna-Eleni; Perrakis, Anastassis; Taraviras, Stavros; Lygerou, Zoi

2011-01-01

Development and homeostasis of multicellular organisms relies on an intricate balance between cell proliferation and differentiation. Geminin regulates the cell cycle by directly binding and inhibiting the DNA replication licensing factor Cdt1. Geminin also interacts with transcriptional regulators of differentiation and chromatin remodelling factors, and its balanced interactions are implicated in proliferation-differentiation decisions during development. Here, we describe Idas (Idas being a cousin of the Gemini in Ancient Greek Mythology), a previously uncharacterised coiled-coil protein related to Geminin. We show that human Idas localizes to the nucleus, forms a complex with Geminin both in cells and in vitro through coiled-coil mediated interactions, and can change Geminin subcellular localization. Idas does not associate with Cdt1 and prevents Geminin from binding to Cdt1 in vitro. Idas depletion from cells affects cell cycle progression; cells accumulate in S phase and are unable to efficiently progress to mitosis. Idas protein levels decrease in anaphase, whereas its overexpression causes mitotic defects. During development, we show that Idas exhibits high level expression in the choroid plexus and the cortical hem of the mouse telencephalon. Our data highlight Idas as a novel Geminin binding partner, implicated in cell cycle progression, and a putative regulator of proliferation-differentiation decisions during development. PMID:21543332

CCND1-CDK4-mediated cell cycle progression provides a competitive advantage for human hematopoietic stem cells in vivo.

Science.gov (United States)

Mende, Nicole; Kuchen, Erika E; Lesche, Mathias; Grinenko, Tatyana; Kokkaliaris, Konstantinos D; Hanenberg, Helmut; Lindemann, Dirk; Dahl, Andreas; Platz, Alexander; Höfer, Thomas; Calegari, Federico; Waskow, Claudia

2015-07-27

Maintenance of stem cell properties is associated with reduced proliferation. However, in mouse hematopoietic stem cells (HSCs), loss of quiescence results in a wide range of phenotypes, ranging from functional failure to extensive self-renewal. It remains unknown whether the function of human HSCs is controlled by the kinetics of cell cycle progression. Using human HSCs and human progenitor cells (HSPCs), we report here that elevated levels of CCND1-CDK4 complexes promoted the transit from G0 to G1 and shortened the G1 cell cycle phase, resulting in protection from differentiation-inducing signals in vitro and increasing human leukocyte engraftment in vivo. Further, CCND1-CDK4 overexpression conferred a competitive advantage without impacting HSPC numbers. In contrast, accelerated cell cycle progression mediated by elevated levels of CCNE1-CDK2 led to the loss of functional HSPCs in vivo. Collectively, these data suggest that the transition kinetics through the early cell cycle phases are key regulators of human HSPC function and important for lifelong hematopoiesis. © 2015 Mende et al.

Cdk1 activity acts as a quantitative platform for coordinating cell cycle progression with periodic transcription

Science.gov (United States)

Banyai, Gabor; Baïdi, Feriel; Coudreuse, Damien; Szilagyi, Zsolt

2016-01-01

Cell proliferation is regulated by cyclin-dependent kinases (Cdks) and requires the periodic expression of particular gene clusters in different cell cycle phases. However, the interplay between the networks that generate these transcriptional oscillations and the core cell cycle machinery remains largely unexplored. In this work, we use a synthetic regulable Cdk1 module to demonstrate that periodic expression is governed by quantitative changes in Cdk1 activity, with different clusters directly responding to specific activity levels. We further establish that cell cycle events neither participate in nor interfere with the Cdk1-driven transcriptional program, provided that cells are exposed to the appropriate Cdk1 activities. These findings contrast with current models that propose self-sustained and Cdk1-independent transcriptional oscillations. Our work therefore supports a model in which Cdk1 activity serves as a quantitative platform for coordinating cell cycle transitions with the expression of critical genes to bring about proper cell cycle progression. PMID:27045731

International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO). 2008 progress report

International Nuclear Information System (INIS)

2009-02-01

The purpose of the work is to review the progress of the IAEA international project for innovative reactors and fuel cycle technologies (INPRO). The publication reports about the recognition of INPRO and on general Information on INPRO, its strengths, memberships, collaboration with other international initiatives, the INPRO organization and management and the history of INPRO. The section on the progress of INPRO in 2008 contains task 1: INPRO Methodology, task 2: Assessment Studies, task 3: Nuclear Energy Visions for the 21st Century, task 4: Infrastructure and Institutional Innovation, task 5: Common User Considerations and task 6: Collaborative Projects. Conclusions and New Trends are followed by a bibliography. Annex I deals with the INPRO project management in 2008 and Annex II provides a selection of photographs from 2008. Finally a list of acronyms is provided

Effects of (/sup 3/H)UdR on the cell-cycle progression of L1210 cells

Energy Technology Data Exchange (ETDEWEB)

Darzynkiewicz, Z.; Carter, S.; Kimmel, M. (Memorial Sloan-Kettering Cancer Center, New York (USA))

1984-11-01

Tritium-labelled uridine ((/sup 3/H)UdR)perturbs progression of L1210 cells through the mitotic cycle. A slowdown of G/sub 2/ cells is observed 2 hr after addition of 0.5-5.0 ..mu..ci/ml of (/sup 3/H)UdR into cultures. At 2.5-5.0 ..mu..Ci/ml of (/sup 3/H)UdR a slowdown of cell progression through S is also apparent. Additionally, there is an increase in the number of cells with DNA values higher than 4C in cultures growing in the presence of (/sup 3/H)UdR for 8-24 hr. A pulse of (/sup 3/H)UdR of 2 hr duration labels predominantly (95%) cellular RNA. The first cell-cycle effects (G/sub 2/ slowdown) are observed when the amount of the incorporated (/sup 3/H)UdR is such that, on average there are fewer than thirty-six (/sup 3/H) decays per cell which corresponds to approximately 12-19 rads. The S-phase slowdown is seen at a dose of incorporated (/sup 3/H)UdR twice as high as that inducing G/sub 2/ effects. The specific localization of (/sup 3/H)UdR in nucleoli, peripheral nucleoplasm and in cytoplasm, as well as differences in the kinetics of the incorporation in relation to phases of the cell cycle are discussed. Mathematical modelling of the cell-cycle effects of (/sup 3/H)UdR is provided.

Cell cycle progression, but not genotoxic activity, mainly contributes to citrinin-induced renal carcinogenesis

International Nuclear Information System (INIS)

Kuroda, Ken; Ishii, Yuji; Takasu, Shinji; Kijima, Aki; Matsushita, Kohei; Watanabe, Maiko; Takahashi, Haruo; Sugita-Konishi, Yoshiko; Sakai, Hiroki; Yanai, Tokuma; Nohmi, Takehiko; Ogawa, Kumiko; Umemura, Takashi

2013-01-01

Citrinin (CTN) is a food-contaminating mycotoxin that efficiently induces renal tumors in rats. However, the modes of carcinogenic action are still unknown, preventing assessment of the risks of CTN in humans. In the present study, the proliferative effects of CTN and its causal factors were investigated in the kidneys of gpt delta rats. In addition, three in vivo genotoxicity assays (reporter gene mutation using gpt delta rats and comet and micronucleus assays using F344 rats) were performed to clarify whether CTN was genotoxic in vivo. CTN was administrated at 20 and 40 mg/kg/day, the higher dose being the maximal tolerated dose and a nearly carcinogenic dose. In the kidney cortex of gpt delta rats, significant increases in the labeling indices of proliferating cell nuclear antigen (PCNA)-positive cells were observed at all doses of CTN. Increases in the mRNA expression levels of Ccna2, Ccnb1, Ccne1, and its transcription factor E2f1 were also detected, suggesting induction of cell cycle progression at all tested doses of CTN. However, histopathological changes were found only in rats treated with the higher dose of CTN, which was consistent with increases in the mRNA expression levels of mitogenic factors associated with tissue damage/regeneration, such as Hgf and Lcn2, at the same dose. Thus, the proliferative effects of CTN may result not only from compensatory reactions, but also from direct mitogenic action. Western blot analysis showed that ERK phosphorylation was increased at all doses, implying that cell cycle progression may be mediated by activation of the ERK pathway. On the other hand, in vivo genotoxicity analyses were negative, implying that CTN did not have the potential for inducing DNA damage, gene mutations, or chromosomal aberrations. The overall data clearly demonstrated the molecular events underlying CTN-induced cell cycle progression, which could be helpful to understand CTN-induced renal carcinogenesis

Metformin inhibits cell cycle progression of B-cell chronic lymphocytic leukemia cells.

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Bruno, Silvia; Ledda, Bernardetta; Tenca, Claudya; Ravera, Silvia; Orengo, Anna Maria; Mazzarello, Andrea Nicola; Pesenti, Elisa; Casciaro, Salvatore; Racchi, Omar; Ghiotto, Fabio; Marini, Cecilia; Sambuceti, Gianmario; DeCensi, Andrea; Fais, Franco

2015-09-08

B-cell chronic lymphocytic leukemia (CLL) was believed to result from clonal accumulation of resting apoptosis-resistant malignant B lymphocytes. However, it became increasingly clear that CLL cells undergo, during their life, iterative cycles of re-activation and subsequent clonal expansion. Drugs interfering with CLL cell cycle entry would be greatly beneficial in the treatment of this disease. 1, 1-Dimethylbiguanide hydrochloride (metformin), the most widely prescribed oral hypoglycemic agent, inexpensive and well tolerated, has recently received increased attention for its potential antitumor activity. We wondered whether metformin has apoptotic and anti-proliferative activity on leukemic cells derived from CLL patients. Metformin was administered in vitro either to quiescent cells or during CLL cell activation stimuli, provided by classical co-culturing with CD40L-expressing fibroblasts. At doses that were totally ineffective on normal lymphocytes, metformin induced apoptosis of quiescent CLL cells and inhibition of cell cycle entry when CLL were stimulated by CD40-CD40L ligation. This cytostatic effect was accompanied by decreased expression of survival- and proliferation-associated proteins, inhibition of signaling pathways involved in CLL disease progression and decreased intracellular glucose available for glycolysis. In drug combination experiments, metformin lowered the apoptotic threshold and potentiated the cytotoxic effects of classical and novel antitumor molecules. Our results indicate that, while CLL cells after stimulation are in the process of building their full survival and cycling armamentarium, the presence of metformin affects this process.

Nuclear reprogramming: kinetics of cell cycle and metabolic progression as determinants of success.

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Sebastian Thomas Balbach

Full Text Available Establishment of totipotency after somatic cell nuclear transfer (NT requires not only reprogramming of gene expression, but also conversion of the cell cycle from quiescence to the precisely timed sequence of embryonic cleavage. Inadequate adaptation of the somatic nucleus to the embryonic cell cycle regime may lay the foundation for NT embryo failure and their reported lower cell counts. We combined bright field and fluorescence imaging of histone H(2b-GFP expressing mouse embryos, to record cell divisions up to the blastocyst stage. This allowed us to quantitatively analyze cleavage kinetics of cloned embryos and revealed an extended and inconstant duration of the second and third cell cycles compared to fertilized controls generated by intracytoplasmic sperm injection (ICSI. Compared to fertilized embryos, slow and fast cleaving NT embryos presented similar rates of errors in M phase, but were considerably less tolerant to mitotic errors and underwent cleavage arrest. Although NT embryos vary substantially in their speed of cell cycle progression, transcriptome analysis did not detect systematic differences between fast and slow NT embryos. Profiling of amino acid turnover during pre-implantation development revealed that NT embryos consume lower amounts of amino acids, in particular arginine, than fertilized embryos until morula stage. An increased arginine supplementation enhanced development to blastocyst and increased embryo cell numbers. We conclude that a cell cycle delay, which is independent of pluripotency marker reactivation, and metabolic restraints reduce cell counts of NT embryos and impede their development.

MMSET deregulation affects cell cycle progression and adhesion regulons in t(4;14) myeloma plasma cells

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Brito, Jose L.R.; Walker, Brian; Jenner, Matthew; Dickens, Nicholas J.; Brown, Nicola J.M.; Ross, Fiona M.; Avramidou, Athanasia; Irving, Julie A.E.; Gonzalez, David; Davies, Faith E.; Morgan, Gareth J.

2009-01-01

Background The recurrent immunoglobulin translocation, t(4;14)(p16;q32) occurs in 15% of multiple myeloma patients and is associated with poor prognosis, through an unknown mechanism. The t(4;14) up-regulates fibroblast growth factor receptor 3 (FGFR3) and multiple myeloma SET domain (MMSET) genes. The involvement of MMSET in the pathogenesis of t(4;14) multiple myeloma and the mechanism or genes deregulated by MMSET upregulation are still unclear. Design and Methods The expression of MMSET was analyzed using a novel antibody. The involvement of MMSET in t(4;14) myelomagenesis was assessed by small interfering RNA mediated knockdown combined with several biological assays. In addition, the differential gene expression of MMSET-induced knockdown was analyzed with expression microarrays. MMSET gene targets in primary patient material was analyzed by expression microarrays. Results We found that MMSET isoforms are expressed in multiple myeloma cell lines, being exclusively up-regulated in t(4;14)-positive cells. Suppression of MMSET expression affected cell proliferation by both decreasing cell viability and cell cycle progression of cells with the t(4;14) translocation. These findings were associated with reduced expression of genes involved in the regulation of cell cycle progression (e.g. CCND2, CCNG1, BRCA1, AURKA and CHEK1), apoptosis (CASP1, CASP4 and FOXO3A) and cell adhesion (ADAM9 and DSG2). Furthermore, we identified genes involved in the latter processes that were differentially expressed in t(4;14) multiple myeloma patient samples. Conclusions In conclusion, dysregulation of MMSET affects the expression of several genes involved in the regulation of cell cycle progression, cell adhesion and survival. PMID:19059936

A novel quantitative model of cell cycle progression based on cyclin-dependent kinases activity and population balances.

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Pisu, Massimo; Concas, Alessandro; Cao, Giacomo

2015-04-01

Cell cycle regulates proliferative cell capacity under normal or pathologic conditions, and in general it governs all in vivo/in vitro cell growth and proliferation processes. Mathematical simulation by means of reliable and predictive models represents an important tool to interpret experiment results, to facilitate the definition of the optimal operating conditions for in vitro cultivation, or to predict the effect of a specific drug in normal/pathologic mammalian cells. Along these lines, a novel model of cell cycle progression is proposed in this work. Specifically, it is based on a population balance (PB) approach that allows one to quantitatively describe cell cycle progression through the different phases experienced by each cell of the entire population during its own life. The transition between two consecutive cell cycle phases is simulated by taking advantage of the biochemical kinetic model developed by Gérard and Goldbeter (2009) which involves cyclin-dependent kinases (CDKs) whose regulation is achieved through a variety of mechanisms that include association with cyclins and protein inhibitors, phosphorylation-dephosphorylation, and cyclin synthesis or degradation. This biochemical model properly describes the entire cell cycle of mammalian cells by maintaining a sufficient level of detail useful to identify check point for transition and to estimate phase duration required by PB. Specific examples are discussed to illustrate the ability of the proposed model to simulate the effect of drugs for in vitro trials of interest in oncology, regenerative medicine and tissue engineering. Copyright © 2015 Elsevier Ltd. All rights reserved.

Solvent Isotope-induced Equilibrium Perturbation for Isocitrate Lyase

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Quartararo, Christine E.; Hadi, Timin; Cahill, Sean M.; Blanchard, John S.

2014-01-01

Isocitrate lyase (ICL) catalyzes the reversible retro-aldol cleavage of isocitrate to generate glyoxylate and succinate. ICL is the first enzyme of the glyoxylate shunt, which allows for the anaplerosis of citric acid cycle intermediates under nutrient limiting conditions. In Mycobacterium tuberculosis, the source of ICL for these studies, ICL is vital for the persistence phase of the bacteria’s life cycle. Solvent kinetic isotope effects (KIEs) in the direction of isocitrate cleavage of D2OV = 2.0 ± 0.1 and D2O[V/Kisocitrate] = 2.2 ± 0.3 arise from the initial deprotonation of the C2 hydroxyl group of isocitrate or the protonation of the aci-acid of succinate product of the isocitrate aldol cleavage by a solvent-derived proton. This KIE suggested that an equilibrium mixture of all protiated isocitrate, glyoxylate and succinate prepared in D2O, would undergo transient changes in equilibrium concentrations as a result of the solvent KIE and solvent-derived deuterium incorporation into both succinate and isocitrate. No change in the isotopic composition of glyoxylate was expected or observed. We have directly monitored the changing concentrations of all isotopic species of all reactants and products using a combination of NMR spectroscopy and mass spectrometry. Continuous monitoring of glyoxylate by 1H NMR spectroscopy shows a clear equilibrium perturbation in D2O. The final equilibrium isotopic composition of reactants in D2O revealed di-deuterated succinate, protiated glyoxylate, and mono-deuterated isocitrate, with the transient appearance and disappearance of mono-deuterated succinate. A model for the equilibrium perturbation of substrate species, and their time-dependent isotopic composition is presented. PMID:24261638

A Novel Interaction of Ecdysoneless (ECD) Protein with R2TP Complex Component RUVBL1 Is Required for the Functional Role of ECD in Cell Cycle Progression.

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Mir, Riyaz A; Bele, Aditya; Mirza, Sameer; Srivastava, Shashank; Olou, Appolinaire A; Ammons, Shalis A; Kim, Jun Hyun; Gurumurthy, Channabasavaiah B; Qiu, Fang; Band, Hamid; Band, Vimla

2015-12-28

Ecdysoneless (ECD) is an evolutionarily conserved protein whose germ line deletion is embryonic lethal. Deletion of Ecd in cells causes cell cycle arrest, which is rescued by exogenous ECD, demonstrating a requirement of ECD for normal mammalian cell cycle progression. However, the exact mechanism by which ECD regulates cell cycle is unknown. Here, we demonstrate that ECD protein levels and subcellular localization are invariant during cell cycle progression, suggesting a potential role of posttranslational modifications or protein-protein interactions. Since phosphorylated ECD was recently shown to interact with the PIH1D1 adaptor component of the R2TP cochaperone complex, we examined the requirement of ECD phosphorylation in cell cycle progression. Notably, phosphorylation-deficient ECD mutants that failed to bind to PIH1D1 in vitro fully retained the ability to interact with the R2TP complex and yet exhibited a reduced ability to rescue Ecd-deficient cells from cell cycle arrest. Biochemical analyses demonstrated an additional phosphorylation-independent interaction of ECD with the RUVBL1 component of the R2TP complex, and this interaction is essential for ECD's cell cycle progression function. These studies demonstrate that interaction of ECD with RUVBL1, and its CK2-mediated phosphorylation, independent of its interaction with PIH1D1, are important for its cell cycle regulatory function. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

A Critical Role of TET1/2 Proteins in Cell-Cycle Progression of Trophoblast Stem Cells

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Stephanie Chrysanthou

2018-04-01

Full Text Available Summary: The ten-eleven translocation (TET proteins are well known for their role in maintaining naive pluripotency of embryonic stem cells. Here, we demonstrate that, jointly, TET1 and TET2 also safeguard the self-renewal potential of trophoblast stem cells (TSCs and have partially redundant roles in maintaining the epithelial integrity of TSCs. For the more abundantly expressed TET1, we show that this is achieved by binding to critical epithelial genes, notably E-cadherin, which becomes hyper-methylated and downregulated in the absence of TET1. The epithelial-to-mesenchymal transition phenotype of mutant TSCs is accompanied by centrosome duplication and separation defects. Moreover, we identify a role of TET1 in maintaining cyclin B1 stability, thereby acting as facilitator of mitotic cell-cycle progression. As a result, Tet1/2 mutant TSCs are prone to undergo endoreduplicative cell cycles leading to the formation of polyploid trophoblast giant cells. Taken together, our data reveal essential functions of TET proteins in the trophoblast lineage. : TET proteins are well known for their role in pluripotency. Here, Hemberger and colleagues show that TET1 and TET2 are also critical for maintaining the epithelial integrity of trophoblast stem cells. TET1/2 ensure mitotic cell-cycle progression by stabilizing cyclin B1 and by regulating centrosome organization. These insights reveal the importance of TET proteins beyond their role in epigenome remodeling. Keywords: TET proteins, trophoblast stem cells, cell cycle, endoreduplication, self-renewal, mitosis, trophoblast giant cells, differentiation

From Centralized Disassembly to Life Cycle Management: Status and Progress of E-waste Treatment System in China

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Song, Xiaolong; Yang, Jianxin; Lu, Bin; Yang, Dong

2017-01-01

China is now facing e-waste problems from both growing domestic generation and illegal imports. Many stakeholders are involved in the e-waste treatment system due to the complexity of e-waste life cycle. Beginning with the state of the e-waste treatment industry in China, this paper summarizes the latest progress in e-waste management from such aspects as the new edition of the China RoHS Directive, new Treatment List, new funding subsidy standard, and eco-design pilots. Thus, a conceptual model for life cycle management of e-waste is generalized. The operating procedure is to first identify the life cycle stages of the e-waste and extract the important life cycle information. Then, life cycle tools can be used to conduct a systematic analysis to help decide how to maximize the benefits from a series of life cycle engineering processes. Meanwhile, life cycle thinking is applied to improve the legislation relating to e-waste so as to continuously improve the sustainability of the e-waste treatment system. By providing an integrative framework, the life cycle management of e-waste should help to realize sustainable management of e-waste in developing countries.

The 2nd State of the Carbon Cycle Report (SOCCR-2): Process, Progress and Institutional Context

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Shrestha, G.; Cavallaro, N.; Zhu, Z.; Larson, E. K.; Butler, J. H.

2017-12-01

Over 200 scientists and program managers from U.S., Mexican and Canadian government and non-government institutions have been collaborating on SOCCR-2 since 2015. Responding to the U.S. Global Change Research Act (1990) and the U.S. Carbon Cycle Science Plan (2011), this special Sustained National Climate Assessment report covers many of the GCRA mandated sectors such as agriculture, energy, forestry, aquatic systems, coasts, wetlands, atmospheric and human social systems, integrating the scientific uncertainties and analyzing the effects of global change on the carbon cycle and vice versa, including projections for both human- induced and natural changes. This presentation covers the SOCCR-2 process, progress and institutional context, providing a historical perspective on the interagency instruments and mechanisms that have facilitated the last decades of carbon cycle science reflected in SOCCR-2.

Bioenergetic coupling between membrane transport systems and biosynthetic pathways essential for cell cycle progression

International Nuclear Information System (INIS)

Leister, K.J.; Cutry, A.F.; Wenner, C.E.

1986-01-01

Recently, it has been shown that there exists a point in the cell cycle (approximately 2 h prior to S phase entry) when (Na + /K + )ATPase pump activity is no longer needed for progression through the cycle. These data suggests that pump activity is critical in the biosynthetic processes which enables the cell to proceed through the G 1 phase. A scheme is proposed which is currently being tested that (Na + /K + )ATPase pump activity serves as the driving force in the regulation of other membrane transport processes critical for cell proliferation. For example, in post-confluent quiescent C3H-10T1/2 fibroblasts, when [K + ]/sub o/ is lowered just below the K/sub m/ of the pump for K + there is a 10-fold increase in 3 H-uridine uptake into both acid soluble and insoluble cell fractions. By modulation of the pump in this manner, glucose utilization is enhanced whereas inhibition of the pump by ouabain suppresses glucose utilization. In both methods of affecting the pump, 3 H-leucine incorporation is inhibited. Electron acceptors that influence the redox state of the cell have been shown to both stimulate or inhibit cell cycle progression. Under conditions where [K + ]/sub o/ is lowered, the nucleoside uptake responses observed were modified by electron acceptors depending on the ability to oxidize NAD(P)H directly or to interact with a cytochrome-like component, (e.g. phenazine methosulfate) reversed the enhanced uridine uptake and p-phenylene diamine further enhanced the uridine uptake response. These findings suggest that a plasma membrane redox system (presumably cyt-c like) is linked to nucleoside transport which is subject to (Na + /K + )ATPase activity

Creeping of hysteresis cycles; Reptation des cycles d'hysteresis

Energy Technology Data Exchange (ETDEWEB)

Neel, L [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires; Faculte des Sciences de Grenoble, 38 (France)

1959-07-01

Creeping consists of a kind of progressive translation of dissymmetric ferromagnetic hysteresis cycles as a function of the order number of the cycle. It is interpreted here by means of a probable coupling field, the existence of which is connected to a statistical conception of the distribution of the elementary regions. (author) [French] La reptation consiste en une sorte de translation progressive des cycles d'hysteresis ferromagnetiques dissymetriques en fonction du numero d'ordre du cycle. L'auteur l'interprete au moyen d'un champ aleatoire de couplage dont l'existence est liee a une conception statistique de la distribution des domaines elementaires. (auteur)

Increasing L-threonine production in Escherichia coli by engineering the glyoxylate shunt and the L-threonine biosynthesis pathway.

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Zhao, Hui; Fang, Yu; Wang, Xiaoyuan; Zhao, Lei; Wang, Jianli; Li, Ye

2018-04-30

L-threonine is an important amino acid that can be added in food, medicine, or feed. Here, the influence of glyoxylate shunt on an L-threonine producing strain Escherichia coli TWF001 has been studied. The gene iclR was deleted, and the native promoter of the aceBA operon was replaced by the trc promoter in the chromosome of TWF001, the resulting strainTWF004 could produce 0.39 g L-threonine from1 g glucose after 36-h flask cultivation. Further replacing the native promoter of aspC by the trc promoter in the chromosome of TWF004 resulted in the strain TWF006. TWF006 could produce 0.42 g L-threonine from 1 g glucose after 36-h flask cultivation. Three key genes in the biosynthetic pathway of L-threonine, thrA * (a mutated thrA), thrB, and thrC were overexpressed in TWF006, resulting the strain TWF006/pFW01-thrA * BC. TWF006/pFW01-thrA * BC could produce 0.49 g L-threonine from 1 g glucose after 36-h flask cultivation. Next, the genes asd, rhtA, rhtC, or thrE were inserted into the plasmid TWF006/pFW01-thrA * BC, and TWF006 was transformed with these plasmids, resulting the strains TWF006/pFW01-thrA * BC-asd, TWF006/pFW01-thrA * BC-rhtA, TWF006/pFW01-thrA * BC-rhtC, and TWF006/pFW01-thrA * BC-thrE, respectively. These four strains could produce more L-threonine than the control strain, and the highest yield was produced by TWF006/pFW01-thrA * BC-asd; after 36-h flask cultivation, TWF006/pFW01-thrA * BC-asd could produce 15.85 g/l L-threonine, i.e., 0.53 g L-threonine per 1 g glucose, which is a 70% increase relative to the control strain TWF001. The results suggested that the combined engineering of glyoxylate shunt and L-threonine biosynthesis pathway could significantly increase the L-threonine production in E. coli.

Effects of arsenite on cell cycle progression in a human bladder cancer cell line

International Nuclear Information System (INIS)

Hernandez-Zavala, A.; Cordova, E.; Razo, L.M. del; Cebrian, M.E.; Garrido, E.

2005-01-01

Bladder cancer is one of the most important diseases associated with arsenic (As) exposure in view of its high prevalence and mortality rate. Experimental studies have shown that As exposure induces cell proliferation in the bladder of sodium arsenite (iAsIII) subchronically treated mice. However, there is little available information on its effects on the cell cycle of bladder cells. Thus, our purpose was to evaluate the effects of iAsIII on cell cycle progression and the response of p53 and p21 on the human-derived epithelial bladder cell line HT1197. iAsIII treatment (1-10 μM) for 24 h induced a dose-dependent increase in the proportion of cells in S-phase, which reached 65% at the highest dose. A progressive reduction in cell proliferation was also observed. BrdU was incorporated to cellular DNA in an interrupted form, suggesting an incomplete DNA synthesis. The time-course of iAsIII effects (10 μM) showed an increase in p53 protein content and a transient increase in p21 protein levels accompanying the changes in S-phase. These effects were correlated with iAs concentrations inside the cells, which were not able to metabolize inorganic arsenic. Our findings suggest that p21 was not able to block CDK2-cyclin E complex activity and was therefore unable to arrest cells in G1 allowing their progression into the S-phase. Further studies are needed to ascertain the mechanisms underlying the effects of iAsIII on the G1 to S phase transition in bladder cells

Identification of a novel centrosomal protein CrpF46 involved in cell cycle progression and mitosis

International Nuclear Information System (INIS)

Wei Yi; Shen Enzhi; Zhao Na; Liu Qian; Fan Jinling; Marc, Jan; Wang Yongchao; Sun Le; Liang Qianjin

2008-01-01

A novel centrosome-related protein Crp F46 was detected using a serum F46 from a patient suffering from progressive systemic sclerosis. We identified the protein by immunoprecipitation and Western blotting followed by tandem mass spectrometry sequencing. The protein Crp F46 has an apparent molecular mass of ∼ 60 kDa, is highly homologous to a 527 amino acid sequence of the C-terminal portion of the protein Golgin-245, and appears to be a splice variant of Golgin-245. Immunofluorescence microscopy of synchronized HeLa cells labeled with an anti-Crp F46 monoclonal antibody revealed that Crp F46 localized exclusively to the centrosome during interphase, although it dispersed throughout the cytoplasm at the onset of mitosis. Domain analysis using Crp F46 fragments in GFP-expression vectors transformed into HeLa cells revealed that centrosomal targeting is conferred by a C-terminal coiled-coil domain. Antisense Crp F46 knockdown inhibited cell growth and proliferation and the cell cycle typically stalled at S phase. The knockdown also resulted in the formation of poly-centrosomal and multinucleate cells, which finally became apoptotic. These results suggest that Crp F46 is a novel centrosome-related protein that associates with the centrosome in a cell cycle-dependent manner and is involved in the progression of the cell cycle and M phase mechanism

Akt1 intramitochondrial cycling is a crucial step in the redox modulation of cell cycle progression.

Directory of Open Access Journals (Sweden)

Valeria Gabriela Antico Arciuch

2009-10-01

Full Text Available Akt is a serine/threonine kinase involved in cell proliferation, apoptosis, and glucose metabolism. Akt is differentially activated by growth factors and oxidative stress by sequential phosphorylation of Ser(473 by mTORC2 and Thr(308 by PDK1. On these bases, we investigated the mechanistic connection of H(2O(2 yield, mitochondrial activation of Akt1 and cell cycle progression in NIH/3T3 cell line with confocal microscopy, in vivo imaging, and directed mutagenesis. We demonstrate that modulation by H(2O(2 entails the entrance of cytosolic P-Akt1 Ser(473 to mitochondria, where it is further phosphorylated at Thr(308 by constitutive PDK1. Phosphorylation of Thr(308 in mitochondria determines Akt1 passage to nuclei and triggers genomic post-translational mechanisms for cell proliferation. At high H(2O(2, Akt1-PDK1 association is disrupted and P-Akt1 Ser(473 accumulates in mitochondria in detriment to nuclear translocation; accordingly, Akt1 T308A is retained in mitochondria. Low Akt1 activity increases cytochrome c release to cytosol leading to apoptosis. As assessed by mass spectra, differential H(2O(2 effects on Akt1-PDK interaction depend on the selective oxidation of Cys(310 to sulfenic or cysteic acids. These results indicate that Akt1 intramitochondrial-cycling is central for redox modulation of cell fate.

CCND1–CDK4–mediated cell cycle progression provides a competitive advantage for human hematopoietic stem cells in vivo

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Mende, Nicole; Kuchen, Erika E.; Lesche, Mathias; Grinenko, Tatyana; Kokkaliaris, Konstantinos D.; Hanenberg, Helmut; Lindemann, Dirk; Dahl, Andreas; Platz, Alexander; Höfer, Thomas; Calegari, Federico

2015-01-01

Maintenance of stem cell properties is associated with reduced proliferation. However, in mouse hematopoietic stem cells (HSCs), loss of quiescence results in a wide range of phenotypes, ranging from functional failure to extensive self-renewal. It remains unknown whether the function of human HSCs is controlled by the kinetics of cell cycle progression. Using human HSCs and human progenitor cells (HSPCs), we report here that elevated levels of CCND1–CDK4 complexes promoted the transit from G0 to G1 and shortened the G1 cell cycle phase, resulting in protection from differentiation-inducing signals in vitro and increasing human leukocyte engraftment in vivo. Further, CCND1–CDK4 overexpression conferred a competitive advantage without impacting HSPC numbers. In contrast, accelerated cell cycle progression mediated by elevated levels of CCNE1–CDK2 led to the loss of functional HSPCs in vivo. Collectively, these data suggest that the transition kinetics through the early cell cycle phases are key regulators of human HSPC function and important for lifelong hematopoiesis. PMID:26150472

Monoclonal Antibodies to Intracellular Stages of Cryptosporidium parvum Define Life Cycle Progression In Vitro.

Science.gov (United States)

Wilke, Georgia; Ravindran, Soumya; Funkhouser-Jones, Lisa; Barks, Jennifer; Wang, Qiuling; VanDussen, Kelli L; Stappenbeck, Thaddeus S; Kuhlenschmidt, Theresa B; Kuhlenschmidt, Mark S; Sibley, L David

2018-06-27

Among the obstacles hindering Cryptosporidium research is the lack of an in vitro culture system that supports complete life development and propagation. This major barrier has led to a shortage of widely available anti- Cryptosporidium antibodies and a lack of markers for staging developmental progression. Previously developed antibodies against Cryptosporidium were raised against extracellular stages or recombinant proteins, leading to antibodies with limited reactivity across the parasite life cycle. Here we sought to create antibodies that recognize novel epitopes that could be used to define intracellular development. We identified a mouse epithelial cell line that supported C. parvum growth, enabling immunization of mice with infected cells to create a bank of monoclonal antibodies (MAbs) against intracellular parasite stages while avoiding the development of host-specific antibodies. From this bank, we identified 12 antibodies with a range of reactivities across the parasite life cycle. Importantly, we identified specific MAbs that can distinguish different life cycle stages, such as trophozoites, merozoites, type I versus II meronts, and macrogamonts. These MAbs provide valuable tools for the Cryptosporidium research community and will facilitate future investigation into parasite biology. IMPORTANCE Cryptosporidium is a protozoan parasite that causes gastrointestinal disease in humans and animals. Currently, there is a limited array of antibodies available against the parasite, which hinders imaging studies and makes it difficult to visualize the parasite life cycle in different culture systems. In order to alleviate this reagent gap, we created a library of novel antibodies against the intracellular life cycle stages of Cryptosporidium We identified antibodies that recognize specific life cycle stages in distinctive ways, enabling unambiguous description of the parasite life cycle. These MAbs will aid future investigation into Cryptosporidium biology and

A Critical Review on the Effect of Docosahexaenoic Acid (DHA) on Cancer Cell Cycle Progression.

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Newell, Marnie; Baker, Kristi; Postovit, Lynne M; Field, Catherine J

2017-08-17

Globally, there were 14.1 million new cancer diagnoses and 8.2 million cancer deaths in 2012. For many cancers, conventional therapies are limited in their successes and an improved understanding of disease progression is needed in conjunction with exploration of alternative therapies. The long chain polyunsaturated fatty acid, docosahexaenoic acid (DHA), has been shown to enhance many cellular responses that reduce cancer cell viability and decrease proliferation both in vitro and in vivo. A small number of studies suggest that DHA improves chemotherapy outcomes in cancer patients. It is readily incorporated into cancer cell membranes and, as a result there has been considerable research regarding cell membrane initiated events. For example, DHA has been shown to mediate the induction of apoptosis/reduction of proliferation in vitro and in vivo. However, there is limited research into the effect of DHA on cell cycle regulation in cancer cells and the mechanism(s) by which DHA acts are not fully understood. The purpose of the current review is to provide a critical examination of the literature investigating the ability of DHA to stall progression during different cell cycle phases in cancer cells, as well as the consequences that these changes may have on tumour growth, independently and in conjunction with chemotherapy.

Cell kinetics of hypoxic cells in a murine tumour in vivo: flow cytometric determination of the radiation-induced blockage of cell cycle progression

International Nuclear Information System (INIS)

Rutgers, D.H.; Niessen, D.P.P.; Linden, P.M. van der

1987-01-01

Cells from the small cell population of viable cells in the large necrotic centre of murine M8013 tumours were investigated with respect to their cell kinetics. Flow cytometry (FCM) of this part of subcutaneously transplanted tumours revealed the presence of tumour cells with G1,S and G2 + M phase DNA-contents. These severely hypoxic cells could have stopped cell cycle progression due to the nutritional deprivation, irrespective of their position within the cell cycle. Labelling methods, used to disclose the cell kinetics of this cell population, are hampered by the absence of a transport system in these large necrotic areas. Therefore FCM was used to monitor radiation induced changes in the cell cycle distribution. From this investigation it was concluded that hypoxic cells in the necrotic centre of the M8013 tumour progress through the cell cycle. As well as a cell population with a cell cycle time (Tsub(c)) of approximately 84 hr, a subpopulation with a Tsub(c) of approximately 21 hr occurred. (author)

ROCK inhibition with Y27632 promotes the proliferation and cell cycle progression of cultured astrocyte from spinal cord.

Science.gov (United States)

Yu, Zhiyuan; Liu, Miao; Fu, Peicai; Xie, Minjie; Wang, Wei; Luo, Xiang

2012-12-01

Rho-associated Kinase (ROCK) has been identified as an important regulator of proliferation and cell cycle progression in a number of cell types. Although its effects on astrocyte proliferation have not been well characterized, ROCK has been reported to play important roles in gap junction formation, morphology, and migration of astrocytes. In the present study, our aim was to investigate the effect of ROCK inhibition by [(+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride] (Y27632) on proliferation and DNA synthesis in cultured astrocytes from rat spinal cord and the possible mechanism involved. Western blots showed that treatment of astrocytes with Y27632 increased their expression of cyclin D1, CDK4, and cyclin E, thereby causing cell cycle progression. Furthermore, Y27632-induced astrocyte proliferation was mediated through the extracellular-signal-regulated kinase signaling cascade. These results indicate the importance of ROCK in astrocyte proliferation. Copyright © 2012 Elsevier Ltd. All rights reserved.

S-phase Synchronization Facilitates the Early Progression of Induced-Cardiomyocyte Reprogramming through Enhanced Cell-Cycle Exit.

Science.gov (United States)

Bektik, Emre; Dennis, Adrienne; Pawlowski, Gary; Zhou, Chen; Maleski, Danielle; Takahashi, Satoru; Laurita, Kenneth R; Deschênes, Isabelle; Fu, Ji-Dong

2018-05-04

Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds a great promise for regenerative medicine and has been studied in several major directions. However, cell-cycle regulation, a fundamental biological process, has not been investigated during iCM-reprogramming. Here, our time-lapse imaging on iCMs, reprogrammed by Gata4, Mef2c, and Tbx5 (GMT) monocistronic retroviruses, revealed that iCM-reprogramming was majorly initiated at late-G1- or S-phase and nearly half of GMT-reprogrammed iCMs divided soon after reprogramming. iCMs exited cell cycle along the process of reprogramming with decreased percentage of 5-ethynyl-20-deoxyuridine (EdU)⁺/α-myosin heavy chain (αMHC)-GFP⁺ cells. S-phase synchronization post-GMT-infection could enhance cell-cycle exit of reprogrammed iCMs and yield more GFP high iCMs, which achieved an advanced reprogramming with more expression of cardiac genes than GFP low cells. However, S-phase synchronization did not enhance the reprogramming with a polycistronic-viral vector, in which cell-cycle exit had been accelerated. In conclusion, post-infection synchronization of S-phase facilitated the early progression of GMT-reprogramming through a mechanism of enhanced cell-cycle exit.

A conserved cyclin-binding domain determines functional interplay between anaphase-promoting complex-Cdh1 and cyclin A-Cdk2 during cell cycle progression

DEFF Research Database (Denmark)

Lukas, C; Kramer, E R; Peters, J M

2001-01-01

Periodic activity of the anaphase-promoting complex (APC) ubiquitin ligase determines progression through multiple cell cycle transitions by targeting cell cycle regulators for destruction. At the G(1)/S transition, phosphorylation-dependent dissociation of the Cdh1-activating subunit inhibits...... the APC, allowing stabilization of proteins required for subsequent cell cycle progression. Cyclin-dependent kinases (CDKs) that initiate and maintain Cdh1 phosphorylation have been identified. However, the issue of which cyclin-CDK complexes are involved has been a matter of debate, and the mechanism...... of how cyclin-CDKs interact with APC subunits remains unresolved. Here we substantiate the evidence that mammalian cyclin A-Cdk2 prevents unscheduled APC reactivation during S phase by demonstrating its periodic interaction with Cdh1 at the level of endogenous proteins. Moreover, we identified...

State-of-the-Art Report on the Progress of Nuclear Fuel Cycle Chemistry

International Nuclear Information System (INIS)

Collins, E.D.; DelCul, G.D.; Spencer, B.B.; Jubin, R.T.; Maher, C.; Kim, I.-T.; Lee, H.; Federov, Yu. S.; Saprykin, V.F.; Beznosyuk, V.I.; Kolyadin, A.B.; Baron, P.; Miguirditchian, M.; Sorel, C.; Morita, Y.; Taylor, R.; Khaperskaya, A.; Hill, C.; Malmbeck, R.; Law, J.; Angelis, G. de; Boucher, L.; Xeres, X.; Collins, E.; Mendes, E.; Lee, H.-S.; Inoue, T.; Glatz, J.P.; Kormilitsyn, M.; Uhlir, J.; Ignatiev, V.; Serp, J.; Delpech, S.

2018-01-01

The implementation of advanced nuclear systems requires that new technologies associated with the back end of the fuel cycle are developed. The separation of minor actinides from other fuel components is one of the advanced concepts being studied to help close the nuclear fuel cycle and to improve the long-term effects on the performance of geological repositories. Separating spent fuel elements and subsequently converting them through transmutation into short-lived nuclides should considerably reduce the long-term risks associated with nuclear power generation. R and D programs worldwide are attempting to address such challenges, and many processes for advanced reprocessing and partitioning minor actinides are being developed. This report provides a comprehensive overview of progress on separation chemistry processes, and in particular on the technologies associated with the separation and recovery of minor actinides for recycling so as to help move towards the implementation of advanced fuel cycles. The report examines both aqueous and pyro processes, as well as the status of current and proposed technologies described according to the hierarchy of separations targeting different fuel components. The process criteria that will affect technology down-selection are also reviewed, as are non-proliferation requirements. The maturity of different reprocessing techniques are assessed using a scale based on the technology readiness level, and perspectives for future R and D are reviewed

The effects of slow- and fast-rhythm classical music on progressive cycling to voluntary physical exhaustion.

Science.gov (United States)

Szabo, A; Small, A; Leigh, M

1999-09-01

To investigate, based on the parallel information processing model and arousal hypothesis, whether musical tempo and its manipulation during exercise affect the maximal workload (watts) achieved during progressive cycling. repeated measures experiment that involved one control and four treatment conditions. the experiment was performed in a controlled laboratory environment. twenty-four male and female volunteers, recruited from among a University population, were tested. the data collection proceeded in five counterbalanced test-sessions that included control (C), slow music (SM), fast music (FM) slow to fast music (SFM) and fast to slow music (FSM) interventions. In the last two conditions, musical tempo was changed when the participant's maximal HR reserve has reached 70%. In all test-sessions, participants started to cycle at 50 watts and then the workload was increased in increments of 25 watts every minute until self-declared exhaustion. Maximal ergometer cycling was defined as the workload at the last completed minute of exercise. workload, HR, and postexperimental ratings of test-session preferences were the dependent measures. Significantly higher workload was accomplished in the SFM condition. No between-session differences were seen in HR. The results also yielded significantly better "efficiency", in terms of workload/HR reserve ratio, in the SFM session. PARTICIPANTS preferred the FM and SFM sessions more than the other sessions. Switching to FM during progressive exercise results in the accomplishment of more work without proportional changes in HR. These effects may be due to distraction from fatigue and are, apparently, dependent on the attention capturing strength of the distracting stimulus.

Leg joint power output during progressive resistance FES-LCE cycling in SCI subjects: developing an index of fatigue

Directory of Open Access Journals (Sweden)

Faghri Pouran D

2008-04-01

Full Text Available Abstract Background The purpose of this study was to investigate the biomechanics of the hip, knee and ankle during a progressive resistance cycling protocol in an effort to detect and measure the presence of muscle fatigue. It was hypothesized that knee power output can be used as an indicator of fatigue in order to assess the cycling performance of SCI subjects. Methods Six spinal cord injured subjects (2 incomplete, 4 complete between the ages of twenty and fifty years old and possessing either a complete or incomplete spinal cord injury at or below the fourth cervical vertebra participated in this study. Kinematic data and pedal forces were recorded during cycling at increasing levels of resistance. Ankle, knee and hip power outputs and resultant pedal force were calculated. Ergometer cadence and muscle stimulation intensity were also recorded. Results The main findings of this study were: (a ankle and knee power outputs decreased, whereas hip power output increased with increasing resistance, (b cadence, stimulation intensity and resultant pedal force in that combined order were significant predictors of knee power output and (c knowing the value of these combined predictors at 10 rpm, an index of fatigue can be developed, quantitatively expressing the power capacity of the knee joint with respect to a baseline power level defined as fatigue. Conclusion An index of fatigue was successfully developed, proportionalizing knee power capacity during cycling to a predetermined value of fatigue. The fatigue index value at 0/8th kp, measured 90 seconds into active, unassisted pedaling was 1.6. This indicates initial power capacity at the knee to be 1.6 times greater than fatigue. The fatigue index decreased to 1.1 at 2/8th kp, representing approximately a 30% decrease in the knee's power capacity within a 4 minute timespan. These findings suggest that the present cycling protocol is not sufficient for a rider to gain the benefits of FES and thus

Leg joint power output during progressive resistance FES-LCE cycling in SCI subjects: developing an index of fatigue.

Science.gov (United States)

Haapala, Stephenie A; Faghri, Pouran D; Adams, Douglas J

2008-04-26

The purpose of this study was to investigate the biomechanics of the hip, knee and ankle during a progressive resistance cycling protocol in an effort to detect and measure the presence of muscle fatigue. It was hypothesized that knee power output can be used as an indicator of fatigue in order to assess the cycling performance of SCI subjects. Six spinal cord injured subjects (2 incomplete, 4 complete) between the ages of twenty and fifty years old and possessing either a complete or incomplete spinal cord injury at or below the fourth cervical vertebra participated in this study. Kinematic data and pedal forces were recorded during cycling at increasing levels of resistance. Ankle, knee and hip power outputs and resultant pedal force were calculated. Ergometer cadence and muscle stimulation intensity were also recorded. The main findings of this study were: (a) ankle and knee power outputs decreased, whereas hip power output increased with increasing resistance, (b) cadence, stimulation intensity and resultant pedal force in that combined order were significant predictors of knee power output and (c) knowing the value of these combined predictors at 10 rpm, an index of fatigue can be developed, quantitatively expressing the power capacity of the knee joint with respect to a baseline power level defined as fatigue. An index of fatigue was successfully developed, proportionalizing knee power capacity during cycling to a predetermined value of fatigue. The fatigue index value at 0/8th kp, measured 90 seconds into active, unassisted pedaling was 1.6. This indicates initial power capacity at the knee to be 1.6 times greater than fatigue. The fatigue index decreased to 1.1 at 2/8th kp, representing approximately a 30% decrease in the knee's power capacity within a 4 minute timespan. These findings suggest that the present cycling protocol is not sufficient for a rider to gain the benefits of FES and thus raises speculation as to whether or not progressive resistance

Do progressive goverments undertake different debt burdens? Partisan vs. electoral cycles

Directory of Open Access Journals (Sweden)

I.M. García-Sánchez

2011-06-01

Full Text Available Public debt has traditionally been explained mainly by two political factors: a progressive ideology and the electoral cycle. The aim of this paper is to demonstrate how these two factors influence the behavior of Spanish local governments as regards indebtedness, and also how indebtedness is influenced by the interaction of ideology and the electoral cycle.Different dependence models were estimated using panel data methodology based on a sample comprised of Spanish provincial capitals and towns with populations over 50,000, for a total of 148 town councils. The time frame corresponds to the fiscal years 1988 to 2008, inclusive. The results show that in an electoral year all politicians behave opportunistically, giving rise to an important increase in public debt in relation to municipal revenue, although progressive incumbents incur three times more debt than those of the opposite ideology. Moreover, the presence of conservative parties in government has tended to significantly attenuate this behavior in years prior to elections, whereas progressive or left-wing parties have not. It must also be noted that partisan and electoral business cycles have been mitigated since 2002, when the Budgetary Stability Law came into effect, imposing limits on the debt of subnational administrations.The empirical evidence obtained points to the need to perfect internal and external control mechanisms in order to avoid a breakdown in the stability policy and the risk of debt becoming untenable, thus achieving greater budgetary discipline.RESUMENEl nivel de endeudamiento público ha sido explicado mediante dos factores políticos, principalmente, la ideología progresista y el ciclo electoral. El objetivo de este trabajo es evidenciar como influyen ambos factores en el comportamiento de los municipios españoles en relación con la deuda que estos asumen dada su capacidad, y como este esfuerzo se ve influenciado por la interacción entre los ciclos partidista y

Effects of caffeine on protein phosphorylation and cell cycle progression in X-irradiated two-cell mouse embryos

International Nuclear Information System (INIS)

Jung, Th.; Streffer, C.

1992-01-01

To understand the mechanism of the caffeine-induced uncoupling of mitosis and the cellular reactions to DNA-damaging agents, the authors studied the effects of caffeine treatment on cell cycle progression and protein phosphorylation in two-cell mouse embryos after X-irradiation. Caffeine alone had no effect on timing of and changes in phosphorylation associated with the embryonic cell cycle. In combination with X-rays, caffeine was able to override the radiation induced G 2 block and restored normal timing of these phosphorylation changes after X-irradiation. New additional changes in protein phosphorylation appeared after the combined treatment. Isobutyl-methylxanthine (IBMX), a substance chemically related to caffeine but a more specific inhibitor of the phosphodiesterase that breaks down cyclic AMP, reduced radiation induced G 2 block from 4 to 5 h to about 1 h and restored the cell cycle associated changes in protein phosphorylation. (author)

Effects of caffeine on protein phosphorylation and cell cycle progression in X-irradiated two-cell mouse embryos

Energy Technology Data Exchange (ETDEWEB)

Jung, Th. (AFRC Institute of Animal Physiology and Genetics Research, Babraham (United Kingdom)); Streffer, C. (Essen Univ (Germany). Inst. fuer Medizinische Strahlenbiolgie)

1992-08-01

To understand the mechanism of the caffeine-induced uncoupling of mitosis and the cellular reactions to DNA-damaging agents, the authors studied the effects of caffeine treatment on cell cycle progression and protein phosphorylation in two-cell mouse embryos after X-irradiation. Caffeine alone had no effect on timing of and changes in phosphorylation associated with the embryonic cell cycle. In combination with X-rays, caffeine was able to override the radiation induced G[sub 2] block and restored normal timing of these phosphorylation changes after X-irradiation. New additional changes in protein phosphorylation appeared after the combined treatment. Isobutyl-methylxanthine (IBMX), a substance chemically related to caffeine but a more specific inhibitor of the phosphodiesterase that breaks down cyclic AMP, reduced radiation induced G[sub 2] block from 4 to 5 h to about 1 h and restored the cell cycle associated changes in protein phosphorylation. (author).

Poly(ethyl glyoxylate)-Poly(ethylene oxide) Nanoparticles: Stimuli-Responsive Drug Release via End-to-End Polyglyoxylate Depolymerization.

Science.gov (United States)

Fan, Bo; Gillies, Elizabeth R

2017-08-07

The ability to disrupt polymer assemblies in response to specific stimuli provides the potential to release drugs selectively at certain sites or conditions in vivo. However, most stimuli-responsive delivery systems require many stimuli-initiated events to release drugs. "Self-immolative polymers" offer the potential to provide amplified responses to stimuli as they undergo complete end-to-end depolymerization following the cleavage of a single end-cap. Herein, linker end-caps were developed to conjugate self-immolative poly(ethyl glyoxylate) (PEtG) with poly(ethylene oxide) (PEO) to form amphiphilic block copolymers. These copolymers were self-assembled to form nanoparticles in aqueous solution. Cleavage of the linker end-caps were triggered by a thiol reducing agent, UV light, H 2 O 2 , and combinations of these stimuli, resulting in nanoparticle disintegration. Low stimuli concentrations were effective in rapidly disrupting the nanoparticles. Nile red, doxorubin, and curcumin were encapsulated into the nanoparticles and were selectively released upon application of the appropriate stimulus. The ability to tune the stimuli-responsiveness simply by changing the linker end-cap makes this new platform highly attractive for applications in drug delivery.

Effects of PTEN transfer on cell cycle progression and expression of P27kipl followed by X-ray irradiation

International Nuclear Information System (INIS)

Tian Mei; Wu Congmei; Liu Linlin; Piao Chunji; Li Xiuyi

2007-01-01

Objective: To investigate the effect of pEgr-hPTEN stable transfer combined with irradiation on the cell cycle progression and the expression of cell cycle kinase inhibitor P27 kipl protein of SHG-44 human glioma cells. Methods: pEgr-hPTEN vector containing the exogenous wild type PTEN gene was transfected into SHG-44 cells under mediation of lipofectamine in vitro, the positive cell clones were selected and amplified by using G418. Western blotting was used to measure the expression of PTEN protein. Transmission electron microscope was adopted to detect the cell ultrastructural changes and flow cytometry was adopted to analysis the changes of cell cycle progression and the expression of P27 kipl in SHG-44-sPTEN cells followed by different doses of X-ray irradiation. Results: Egr-1 promoter could be induced and activated by irradiation and then enhanced the expression of downstream PTEN gene within 5 Gy. The ultrastructure of SHG-44-sPTEN cells had many degenerative changes and many early apoptotic changes including the chromosome condensate around the nuclear envelope. pEgr-hPTEN stable transfer combined with X-ray irradiation could significantly induce G 1 arrest. The expression of P27 kipl proteins increased in SHG-44-sPTEN stable transfected cells. Conclusion: PTEN stable transfer combined with irradiation can significantly induce G 1 arrest. The molecular basis may be correlated with the enhanced expression of PTEN induced by irradiation and increased expression of cell cycle kinase inhibitor P27 kipl . (authors)

Overexpression of catalase delays G0/G1- to S-phase transition during cell cycle progression in mouse aortic endothelial cells.

Science.gov (United States)

Onumah, Ogbeyalu E; Jules, George E; Zhao, Yanfeng; Zhou, LiChun; Yang, Hong; Guo, ZhongMao

2009-06-15

Although it is understood that hydrogen peroxide (H(2)O(2)) promotes cellular proliferation, little is known about its role in endothelial cell cycle progression. To assess the regulatory role of endogenously produced H(2)O(2) in cell cycle progression, we studied the cell cycle progression in mouse aortic endothelial cells (MAECs) obtained from mice overexpressing a human catalase transgene (hCatTg), which destroys H(2)O(2). The hCatTg MAECs displayed a prolonged doubling time compared to wild-type controls (44.0 +/- 4.7 h versus 28.6 +/- 0.8 h, pcatalase inhibitor, prevented the observed diminished growth rate in hCatTg MAECs. Inhibition of catalase activity with aminotriazole abrogated catalase overexpression-induced antiproliferative action. Flow cytometry analysis indicated that the prolonged doubling time was principally due to an extended G(0)/G(1) phase in hCatTg MAECs compared to the wild-type cells (25.0 +/- 0.9 h versus 15.9 +/- 1.4 h, pinhibitors, p21 and p27, which inhibit the Cdk activity required for the G(0)/G(1)- to S-phase transition. Knockdown of p21 and/or p27 attenuated the antiproliferative effect of catalase overexpression in MAECs. These results, together with the fact that catalase is an H(2)O(2) scavenger, suggest that endogenously produced H(2)O(2) mediates MAEC proliferation by fostering the transition from G(0)/G(1) to S phase.

Salicylic acid antagonizes abscisic acid inhibition of shoot growth and cell cycle progression in rice

Science.gov (United States)

Meguro, Ayano; Sato, Yutaka

2014-04-01

We analysed effects of abscisic acid (ABA, a negative regulatory hormone), alone and in combination with positive or neutral hormones, including salicylic acid (SA), on rice growth and expression of cell cycle-related genes. ABA significantly inhibited shoot growth and induced expression of OsKRP4, OsKRP5, and OsKRP6. A yeast two-hybrid assay showed that OsKRP4, OsKRP5, and OsKRP6 interacted with OsCDKA;1 and/or OsCDKA;2. When SA was simultaneously supplied with ABA, the antagonistic effect of SA completely blocked ABA inhibition. SA also blocked ABA inhibition of DNA replication and thymidine incorporation in the shoot apical meristem. These results suggest that ABA arrests cell cycle progression by inducing expression of OsKRP4, OsKRP5, and OsKRP6, which inhibit the G1/S transition, and that SA antagonizes ABA by blocking expression of OsKRP genes.

Phosphorylation of mitogen-activated protein kinase (MAPK) is required for cytokinesis and progression of cell cycle in tobacco BY-2 cells.

Science.gov (United States)

Ma, Zhaowu; Yu, Guanghui

2010-02-15

The role of mitogen-activated protein kinase (MAPK) in plant cytokinesis remains largely uncharacterized. To elucidate its role, tobacco Bright Yellow-2 (BY-2) cells have been synchronized using a two-step procedure, and the different phases of the cell cycle identified by Histone 4 gene expression and the mitotic index. MAPK expression was analyzed by semi-quantitative (SQ) RT-PCR and protein gel blot analysis for phosphorylated MAPK during cell cycle progression. The SQ RT-PCR analysis indicated that MAPK expression is lower in mitosis than in interphase (G1, G2 and S). However, the amount of phosphorylated MAPK remained stable throughout the cell cycle, indicating that MAPK activity is predominantly regulated at the post-translational level and that phosphorylation of MAPK plays an important role in mitosis. Application of the specific MAPK phosphorylation inhibitor U0126 revealed that while U0126 treatment decreases the phosphorylation of MAPK and the progression from telophase to early cytokinesis is significantly inhibited. The formation of the phragmoplast is also negatively affected at this stage. These results demonstrate that MAPK phosphorylation is involved in the formation of the cell plate within the phragmoplast during cytokinesis and that MAPK predominantly functions during the cytokinesis stage of the cell cycle in tobacco BY-2 cells. Copyright 2009 Elsevier GmbH. All rights reserved.

Cytolethal distending toxin: a conserved bacterial genotoxin that blocks cell cycle progression, leading to apoptosis of a broad range of mammalian cell lineages.

Science.gov (United States)

Jinadasa, Rasika N; Bloom, Stephen E; Weiss, Robert S; Duhamel, Gerald E

2011-07-01

Cytolethal distending toxin (CDT) is a heterotrimeric AB-type genotoxin produced by several clinically important Gram-negative mucocutaneous bacterial pathogens. Irrespective of the bacterial species of origin, CDT causes characteristic and irreversible cell cycle arrest and apoptosis in a broad range of cultured mammalian cell lineages. The active subunit CdtB has structural homology with the phosphodiesterase family of enzymes including mammalian DNase I, and alone is necessary and sufficient to account for cellular toxicity. Indeed, mammalian cells treated with CDT initiate a DNA damage response similar to that elicited by ionizing radiation-induced DNA double strand breaks resulting in cell cycle arrest and apoptosis. The mechanism of CDT-induced apoptosis remains incompletely understood, but appears to involve both p53-dependent and -independent pathways. While epithelial, endothelial and fibroblast cell lines respond to CDT by undergoing arrest of cell cycle progression resulting in nuclear and cytoplasmic distension that precedes apoptotic cell death, cells of haematopoietic origin display rapid apoptosis following a brief period of cell cycle arrest. In this review, the ecology of pathogens producing CDT, the molecular biology of bacterial CDT and the molecular mechanisms of CDT-induced cytotoxicity are critically appraised. Understanding the contribution of a broadly conserved bacterial genotoxin that blocks progression of the mammalian cell cycle, ultimately causing cell death, should assist with elucidating disease mechanisms for these important pathogens.

Discovering biological progression underlying microarray samples.

Directory of Open Access Journals (Sweden)

Peng Qiu

2011-04-01

Full Text Available In biological systems that undergo processes such as differentiation, a clear concept of progression exists. We present a novel computational approach, called Sample Progression Discovery (SPD, to discover patterns of biological progression underlying microarray gene expression data. SPD assumes that individual samples of a microarray dataset are related by an unknown biological process (i.e., differentiation, development, cell cycle, disease progression, and that each sample represents one unknown point along the progression of that process. SPD aims to organize the samples in a manner that reveals the underlying progression and to simultaneously identify subsets of genes that are responsible for that progression. We demonstrate the performance of SPD on a variety of microarray datasets that were generated by sampling a biological process at different points along its progression, without providing SPD any information of the underlying process. When applied to a cell cycle time series microarray dataset, SPD was not provided any prior knowledge of samples' time order or of which genes are cell-cycle regulated, yet SPD recovered the correct time order and identified many genes that have been associated with the cell cycle. When applied to B-cell differentiation data, SPD recovered the correct order of stages of normal B-cell differentiation and the linkage between preB-ALL tumor cells with their cell origin preB. When applied to mouse embryonic stem cell differentiation data, SPD uncovered a landscape of ESC differentiation into various lineages and genes that represent both generic and lineage specific processes. When applied to a prostate cancer microarray dataset, SPD identified gene modules that reflect a progression consistent with disease stages. SPD may be best viewed as a novel tool for synthesizing biological hypotheses because it provides a likely biological progression underlying a microarray dataset and, perhaps more importantly, the

Epigenetic dynamics across the cell cycle

DEFF Research Database (Denmark)

Kheir, Tony Bou; Lund, Anders H.

2010-01-01

Progression of the mammalian cell cycle depends on correct timing and co-ordination of a series of events, which are managed by the cellular transcriptional machinery and epigenetic mechanisms governing genome accessibility. Epigenetic chromatin modifications are dynamic across the cell cycle...... a correct inheritance of epigenetic chromatin modifications to daughter cells. In this chapter, we summarize the current knowledge on the dynamics of epigenetic chromatin modifications during progression of the cell cycle....

The B-MYB transcriptional network guides cell cycle progression and fate decisions to sustain self-renewal and the identity of pluripotent stem cells.

Science.gov (United States)

Zhan, Ming; Riordon, Daniel R; Yan, Bin; Tarasova, Yelena S; Bruweleit, Sarah; Tarasov, Kirill V; Li, Ronald A; Wersto, Robert P; Boheler, Kenneth R

2012-01-01

Embryonic stem cells (ESCs) are pluripotent and have unlimited self-renewal capacity. Although pluripotency and differentiation have been examined extensively, the mechanisms responsible for self-renewal are poorly understood and are believed to involve an unusual cell cycle, epigenetic regulators and pluripotency-promoting transcription factors. Here we show that B-MYB, a cell cycle regulated phosphoprotein and transcription factor critical to the formation of inner cell mass, is central to the transcriptional and co-regulatory networks that sustain normal cell cycle progression and self-renewal properties of ESCs. Phenotypically, B-MYB is robustly expressed in ESCs and induced pluripotent stem cells (iPSCs), and it is present predominantly in a hypo-phosphorylated state. Knockdown of B-MYB results in functional cell cycle abnormalities that involve S, G2 and M phases, and reduced expression of critical cell cycle regulators like ccnb1 and plk1. By conducting gene expression profiling on control and B-MYB deficient cells, ChIP-chip experiments, and integrative computational analyses, we unraveled a highly complex B-MYB-mediated transcriptional network that guides ESC self-renewal. The network encompasses critical regulators of all cell cycle phases and epigenetic regulators, pluripotency transcription factors, and differentiation determinants. B-MYB along with E2F1 and c-MYC preferentially co-regulate cell cycle target genes. B-MYB also co-targets genes regulated by OCT4, SOX2 and NANOG that are significantly associated with stem cell differentiation, embryonic development, and epigenetic control. Moreover, loss of B-MYB leads to a breakdown of the transcriptional hierarchy present in ESCs. These results coupled with functional studies demonstrate that B-MYB not only controls and accelerates cell cycle progression in ESCs it contributes to fate decisions and maintenance of pluripotent stem cell identity.

Down-regulation of tricarboxylic acid (TCA) cycle genes blocks progression through the first mitotic division in Caenorhabditis elegans embryos.

Science.gov (United States)

Rahman, Mohammad M; Rosu, Simona; Joseph-Strauss, Daphna; Cohen-Fix, Orna

2014-02-18

The cell cycle is a highly regulated process that enables the accurate transmission of chromosomes to daughter cells. Here we uncover a previously unknown link between the tricarboxylic acid (TCA) cycle and cell cycle progression in the Caenorhabditis elegans early embryo. We found that down-regulation of TCA cycle components, including citrate synthase, malate dehydrogenase, and aconitase, resulted in a one-cell stage arrest before entry into mitosis: pronuclear meeting occurred normally, but nuclear envelope breakdown, centrosome separation, and chromosome condensation did not take place. Mitotic entry is controlled by the cyclin B-cyclin-dependent kinase 1 (Cdk1) complex, and the inhibitory phosphorylation of Cdk1 must be removed in order for the complex to be active. We found that following down-regulation of the TCA cycle, cyclin B levels were normal but CDK-1 remained inhibitory-phosphorylated in one-cell stage-arrested embryos, indicative of a G2-like arrest. Moreover, this was not due to an indirect effect caused by checkpoint activation by DNA damage or replication defects. These observations suggest that CDK-1 activation in the C. elegans one-cell embryo is sensitive to the metabolic state of the cell, and that down-regulation of the TCA cycle prevents the removal of CDK-1 inhibitory phosphorylation. The TCA cycle was previously shown to be necessary for the development of the early embryo in mammals, but the molecular processes affected were not known. Our study demonstrates a link between the TCA cycle and a specific cell cycle transition in the one-cell stage embryo.

Temporal fluxomics reveals oscillations in TCA cycle flux throughout the mammalian cell cycle.

Science.gov (United States)

Ahn, Eunyong; Kumar, Praveen; Mukha, Dzmitry; Tzur, Amit; Shlomi, Tomer

2017-11-06

Cellular metabolic demands change throughout the cell cycle. Nevertheless, a characterization of how metabolic fluxes adapt to the changing demands throughout the cell cycle is lacking. Here, we developed a temporal-fluxomics approach to derive a comprehensive and quantitative view of alterations in metabolic fluxes throughout the mammalian cell cycle. This is achieved by combining pulse-chase LC-MS-based isotope tracing in synchronized cell populations with computational deconvolution and metabolic flux modeling. We find that TCA cycle fluxes are rewired as cells progress through the cell cycle with complementary oscillations of glucose versus glutamine-derived fluxes: Oxidation of glucose-derived flux peaks in late G1 phase, while oxidative and reductive glutamine metabolism dominates S phase. These complementary flux oscillations maintain a constant production rate of reducing equivalents and oxidative phosphorylation flux throughout the cell cycle. The shift from glucose to glutamine oxidation in S phase plays an important role in cell cycle progression and cell proliferation. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Phenylpropanoid 2,3-dioxygenase involved in the cleavage of the ferulic acid side chain to form vanillin and glyoxylic acid in Vanilla planifolia.

Science.gov (United States)

Negishi, Osamu; Negishi, Yukiko

2017-09-01

Enzyme catalyzing the cleavage of the phenylpropanoid side chain was partially purified by ion exchange and gel filtration column chromatography after (NH 4 ) 2 SO 4 precipitation. Enzyme activities were dependent on the concentration of dithiothreitol (DTT) or glutathione (GSH) and activated by addition of 0.5 mM Fe 2+ . Enzyme activity for ferulic acid was as high as for 4-coumaric acid in the presence of GSH, suggesting that GSH acts as an endogenous reductant in vanillin biosynthesis. Analyses of the enzymatic reaction products with quantitative NMR (qNMR) indicated that an amount of glyoxylic acid (GA) proportional to vanillin was released from ferulic acid by the enzymatic reaction. These results suggest that phenylpropanoid 2,3-dioxygenase is involved in the cleavage of the ferulic acid side chain to form vanillin and GA in Vanilla planifolia.

β-catenin at the centrosome: discrete pools of β-catenin communicate during mitosis and may co-ordinate centrosome functions and cell cycle progression.

Science.gov (United States)

Mbom, Bertrade C; Nelson, W James; Barth, Angela

2013-09-01

Beta-catenin is a multifunctional protein with critical roles in cell-cell adhesion, Wnt-signaling and the centrosome cycle. Whereas the roles of β-catenin in cell-cell adhesion and Wnt-signaling have been studied extensively, the mechanism(s) involving β-catenin in centrosome functions are poorly understood. β-Catenin localizes to centrosomes and promotes mitotic progression. NIMA-related protein kinase 2 (Nek2), which stimulates centrosome separation, binds to and phosphorylates β-catenin. β-Catenin interacting proteins involved in Wnt signaling such as adenomatous polyposis coli, Axin, and GSK3β, are also localized at centrosomes and play roles in promoting mitotic progression. Additionally, proteins associated with cell-cell adhesion sites, such as dynein, regulate mitotic spindle positioning. These roles of proteins at the cell cortex and Wnt signaling that involve β-catenin indicate a cross-talk between different sub-cellular sites in the cell at mitosis, and that different pools of β-catenin may co-ordinate centrosome functions and cell cycle progression. © 2013 WILEY Periodicals, Inc.

Systematic engineering of TCA cycle for optimal production of a four-carbon platform chemical 4-hydroxybutyric acid in Escherichia coli.

Science.gov (United States)

Choi, Sol; Kim, Hyun Uk; Kim, Tae Yong; Lee, Sang Yup

2016-11-01

To address climate change and environmental problems, it is becoming increasingly important to establish biorefineries for the production of chemicals from renewable non-food biomass. Here we report the development of Escherichia coli strains capable of overproducing a four-carbon platform chemical 4-hybroxybutyric acid (4-HB). Because 4-HB production is significantly affected by aeration level, genome-scale metabolic model-based engineering strategies were designed under aerobic and microaerobic conditions with emphasis on oxidative/reductive TCA branches and glyoxylate shunt. Several different metabolic engineering strategies were employed to develop strains suitable for fermentation both under aerobic and microaerobic conditions. It was found that microaerobic condition was more efficient than aerobic condition in achieving higher titer and productivity of 4-HB. The final engineered strain produced 103.4g/L of 4-HB by microaerobic fed-batch fermentation using glycerol. The aeration-dependent optimization strategy of TCA cycle will be useful for developing microbial strains producing other reduced derivative chemicals of TCA cycle intermediates. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Role of insulin-like growth factor-1 (IGF-1) in regulating cell cycle progression

International Nuclear Information System (INIS)

Ma, Qi-lin; Yang, Tian-lun; Yin, Ji-ye; Peng, Zhen-yu; Yu, Min; Liu, Zhao-qian; Chen, Fang-ping

2009-01-01

Aims: Insulin-like growth factor-1 (IGF-1) is a polypeptide protein hormone, similar in molecular structure to insulin, which plays an important role in cell migration, cell cycle progression, cell survival and proliferation. In this study, we investigated the possible mechanisms of IGF-1 mediated cell cycle redistribution and apoptosis of vascular endothelial cells. Method: Human umbilical vein endothelial cells (HUVECs) were pretreated with 0.1, 0.5, or 2.5 μg/mL of IGF-1 for 30 min before the addition of Ang II. Cell cycle redistribution and apoptosis were examined by flow cytometry. Expression of Ang II type 1 (AT 1 ) mRNA and cyclin E protein were determined by RT-PCR and Western blot, respectively. Results: Ang II (1 μmol/L) induced HUVECs arrested at G 0 /G 1 , enhanced the expression level of AT 1 mRNA in a time-dependent manner, reduced the enzymatic activity of nitric oxide synthase (NOS) and nitric oxide (NO) content as well as the expression level of cyclin E protein. However, IGF-1 enhanced NOS activity, NO content, and the expression level of cyclin E protein, and reduced the expression level of AT 1 mRNA. L-NAME significantly counteracted these effects of IGF-1. Conclusions: Our data suggests that IGF-1 can reverse vascular endothelial cells arrested at G 0 /G 1 and apoptosis induced by Ang II, which might be mediated via a NOS-NO signaling pathway and is likely associated with the expression levels of AT1 mRNA and cyclin E proteins.

Tangeretin and its metabolite 4'-hydroxytetramethoxyflavone attenuate EGF-stimulated cell cycle progression in hepatocytes; role of inhibition at the level of mTOR/p70S6K.

Science.gov (United States)

Cheng, Z; Surichan, S; Ruparelia, K; Arroo, R; Boarder, M R

2011-04-01

The mechanisms by which the dietary compound tangeretin has anticancer effects may include acting as a prodrug, forming an antiproliferative product in cancer cells. Here we show that tangeretin also inhibits cell cycle progression in hepatocytes and investigate the role of its primary metabolite 4'-hydroxy-5,6,7,8-tetramethoxyflavone (4'-OH-TMF) in this effect. We used epidermal growth factor (EGF)-stimulated rat hepatocytes, with [(3)H]-thymidine incorporation into DNA as an index of progression to S-phase of the cell cycle, and Western blots for phospho-proteins involved in the cell signalling cascade. Incubation of tangeretin with microsomes expressing CYP1A, or with hepatocytes, generated a primary product we identified as 4'-OH-TMF. Low micromolar concentrations of tangeretin or 4'-OH-TMF gave a concentration-dependent inhibition of EGF-stimulated progression to S-phase while having little effect on cell viability. To determine whether time for conversion of tangeretin to an active metabolite would enhance the inhibitory effect we used long pre-incubations; this reduced the inhibitory effect, in parallel with a reduction in the concentration of tangeretin. The EGF-stimulation of hepatocyte cell cycle progression requires signalling through Akt/mTOR/p70S6K kinase cascades. The tangeretin metabolite 4'-OH-TMF selectively inhibited S6K phosphorylation in the absence of significant inhibition of upstream Akt activity, suggesting an effect at the level of mTOR. Tangeretin and 4'-OH-TMF both inhibit cell cycle progression in primary hepatocytes. The inhibition of p70S6K phosphorylation by 4'-OH-TMF raises the possibility that inhibition of the mTOR pathway may contribute to the anticancer influence of a flavonoid-rich diet. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

microRNA-365, down-regulated in colon cancer, inhibits cell cycle progression and promotes apoptosis of colon cancer cells by probably targeting Cyclin D1 and Bcl-2.

Science.gov (United States)

Nie, Jing; Liu, Lin; Zheng, Wei; Chen, Lin; Wu, Xin; Xu, Yingxin; Du, Xiaohui; Han, Weidong

2012-01-01

Deregulated microRNAs participate in carcinogenesis and cancer progression, but their roles in cancer development remain unclear. In this study, miR-365 expression was found to be downregulated in human colon cancer tissues as compared with that in matched non-neoplastic mucosa tissues, and its downregulation was correlated with cancer progression and poor survival in colon cancer patients. Functional studies revealed that restoration of miR-365 expression inhibited cell cycle progression, promoted 5-fluorouracil-induced apoptosis and repressed tumorigenicity in colon cancer cell lines. Furthermore, bioinformatic prediction and experimental validation were used to identify miR-365 target genes and indicated that the antitumor effects of miR-365 were probably mediated by its targeting and repression of Cyclin D1 and Bcl-2 expression, thus inhibiting cell cycle progression and promoting apoptosis. These results suggest that downregulation of miR-365 in colon cancer may have potential applications in prognosis prediction and gene therapy in colon cancer patients.

Role of insulin-like growth factor-1 (IGF-1) in regulating cell cycle progression

Energy Technology Data Exchange (ETDEWEB)

Ma, Qi-lin; Yang, Tian-lun [Department of Cardiology, Xiangya Hospital, Central South University, Changsha 410008, Hunan (China); Yin, Ji-ye [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan (China); Peng, Zhen-yu [Department of Cardiology, Xiangya Hospital, Central South University, Changsha 410008, Hunan (China); Yu, Min [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan (China); Liu, Zhao-qian, E-mail: liuzhaoqian63@126.com [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan (China); Chen, Fang-ping, E-mail: xychenfp@public.cs.hn.Cn [Department of Haematology, Xiangya Hospital, Central South University, Changsha 410008, Hunan (China)

2009-11-06

Aims: Insulin-like growth factor-1 (IGF-1) is a polypeptide protein hormone, similar in molecular structure to insulin, which plays an important role in cell migration, cell cycle progression, cell survival and proliferation. In this study, we investigated the possible mechanisms of IGF-1 mediated cell cycle redistribution and apoptosis of vascular endothelial cells. Method: Human umbilical vein endothelial cells (HUVECs) were pretreated with 0.1, 0.5, or 2.5 {mu}g/mL of IGF-1 for 30 min before the addition of Ang II. Cell cycle redistribution and apoptosis were examined by flow cytometry. Expression of Ang II type 1 (AT{sub 1}) mRNA and cyclin E protein were determined by RT-PCR and Western blot, respectively. Results: Ang II (1 {mu}mol/L) induced HUVECs arrested at G{sub 0}/G{sub 1}, enhanced the expression level of AT{sub 1} mRNA in a time-dependent manner, reduced the enzymatic activity of nitric oxide synthase (NOS) and nitric oxide (NO) content as well as the expression level of cyclin E protein. However, IGF-1 enhanced NOS activity, NO content, and the expression level of cyclin E protein, and reduced the expression level of AT{sub 1} mRNA. L-NAME significantly counteracted these effects of IGF-1. Conclusions: Our data suggests that IGF-1 can reverse vascular endothelial cells arrested at G{sub 0}/G{sub 1} and apoptosis induced by Ang II, which might be mediated via a NOS-NO signaling pathway and is likely associated with the expression levels of AT1 mRNA and cyclin E proteins.

Targeted Deletion of a Plasmodium Site-2 Protease Impairs Life Cycle Progression in the Mammalian Host.

Science.gov (United States)

Koussis, Konstantinos; Goulielmaki, Evi; Chalari, Anna; Withers-Martinez, Chrislaine; Siden-Kiamos, Inga; Matuschewski, Kai; Loukeris, Thanasis G

2017-01-01

Site-2 proteases (S2P) belong to the M50 family of metalloproteases, which typically perform essential roles by mediating activation of membrane-bound transcription factors through regulated intramembrane proteolysis (RIP). Protease-dependent liberation of dormant transcription factors triggers diverse cellular responses, such as sterol regulation, Notch signalling and the unfolded protein response. Plasmodium parasites rely on regulated proteolysis for controlling essential pathways throughout the life cycle. In this study we examine the Plasmodium-encoded S2P in a murine malaria model and show that it is expressed in all stages of Plasmodium development. Localisation studies by endogenous gene tagging revealed that in all invasive stages the protein is in close proximity to the nucleus. Ablation of PbS2P by reverse genetics leads to reduced growth rates during liver and blood infection and, hence, virulence attenuation. Strikingly, absence of PbS2P was compatible with parasite life cycle progression in the mosquito and mammalian hosts under physiological conditions, suggesting redundant or dispensable roles in vivo.

Targeted Deletion of a Plasmodium Site-2 Protease Impairs Life Cycle Progression in the Mammalian Host.

Directory of Open Access Journals (Sweden)

Konstantinos Koussis

Full Text Available Site-2 proteases (S2P belong to the M50 family of metalloproteases, which typically perform essential roles by mediating activation of membrane-bound transcription factors through regulated intramembrane proteolysis (RIP. Protease-dependent liberation of dormant transcription factors triggers diverse cellular responses, such as sterol regulation, Notch signalling and the unfolded protein response. Plasmodium parasites rely on regulated proteolysis for controlling essential pathways throughout the life cycle. In this study we examine the Plasmodium-encoded S2P in a murine malaria model and show that it is expressed in all stages of Plasmodium development. Localisation studies by endogenous gene tagging revealed that in all invasive stages the protein is in close proximity to the nucleus. Ablation of PbS2P by reverse genetics leads to reduced growth rates during liver and blood infection and, hence, virulence attenuation. Strikingly, absence of PbS2P was compatible with parasite life cycle progression in the mosquito and mammalian hosts under physiological conditions, suggesting redundant or dispensable roles in vivo.

Brucella abortus Cell Cycle and Infection Are Coordinated.

Science.gov (United States)

De Bolle, Xavier; Crosson, Sean; Matroule, Jean-Yves; Letesson, Jean-Jacques

2015-12-01

Brucellae are facultative intracellular pathogens. The recent development of methods and genetically engineered strains allowed the description of cell-cycle progression of Brucella abortus, including unipolar growth and the ordered initiation of chromosomal replication. B. abortus cell-cycle progression is coordinated with intracellular trafficking in the endosomal compartments. Bacteria are first blocked at the G1 stage, growth and chromosome replication being resumed shortly before reaching the intracellular proliferation compartment. The control mechanisms of cell cycle are similar to those reported for the bacterium Caulobacter crescentus, and they are crucial for survival in the host cell. The development of single-cell analyses could also be applied to other bacterial pathogens to investigate their cell-cycle progression during infection. Copyright © 2015 Elsevier Ltd. All rights reserved.

Closed cycle MHD specialist meeting. Progress report, 1971--1972

International Nuclear Information System (INIS)

Rietjens, L.H.

1972-04-01

Abstracts of the conference papers on closed cycle MHD research are presented. The general areas of discussion are the following: results on closed cycle experiments; plasma properties, and instabilities and stabilization in nonequilibrium plasmas; loss mechanisms, current distributions, electrode effects, boundary layers, and gas dynamic effects; and design concepts of large MHD generators, and nuclear MHD power plants. (GRA)

Tangeretin and its metabolite 4′-hydroxytetramethoxyflavone attenuate EGF-stimulated cell cycle progression in hepatocytes; role of inhibition at the level of mTOR/p70S6K

Science.gov (United States)

Cheng, Z; Surichan, S; Ruparelia, K; Arroo, R; Boarder, MR

2011-01-01

BACKGROUND AND PURPOSE The mechanisms by which the dietary compound tangeretin has anticancer effects may include acting as a prodrug, forming an antiproliferative product in cancer cells. Here we show that tangeretin also inhibits cell cycle progression in hepatocytes and investigate the role of its primary metabolite 4′-hydroxy-5,6,7,8-tetramethoxyflavone (4′-OH-TMF) in this effect. EXPERIMENTAL APPROACH We used epidermal growth factor (EGF)-stimulated rat hepatocytes, with [3H]-thymidine incorporation into DNA as an index of progression to S-phase of the cell cycle, and Western blots for phospho-proteins involved in the cell signalling cascade. KEY RESULTS Incubation of tangeretin with microsomes expressing CYP1A, or with hepatocytes, generated a primary product we identified as 4′-OH-TMF. Low micromolar concentrations of tangeretin or 4′-OH-TMF gave a concentration-dependent inhibition of EGF-stimulated progression to S-phase while having little effect on cell viability. To determine whether time for conversion of tangeretin to an active metabolite would enhance the inhibitory effect we used long pre-incubations; this reduced the inhibitory effect, in parallel with a reduction in the concentration of tangeretin. The EGF-stimulation of hepatocyte cell cycle progression requires signalling through Akt/mTOR/p70S6K kinase cascades. The tangeretin metabolite 4′-OH-TMF selectively inhibited S6K phosphorylation in the absence of significant inhibition of upstream Akt activity, suggesting an effect at the level of mTOR. CONCLUSIONS AND IMPLICATIONS Tangeretin and 4′-OH-TMF both inhibit cell cycle progression in primary hepatocytes. The inhibition of p70S6K phosphorylation by 4′-OH-TMF raises the possibility that inhibition of the mTOR pathway may contribute to the anticancer influence of a flavonoid-rich diet. PMID:21198542

Site-Specific Phosphorylation of Ikaros Induced by Low-Dose Ionizing Radiation Regulates Cell Cycle Progression of B Lymphoblast Through CK2 and AKT Activation

Energy Technology Data Exchange (ETDEWEB)

Cho, Seong-Jun; Kang, Hana [KHNP Radiation Health Institute, Korea Hydro & Nuclear Power Co, Seoul (Korea, Republic of); Kim, Min Young [Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan (Korea, Republic of); Lee, Jung Eun; Kim, Sung Jin; Nam, Seon Young; Kim, Ji Young; Kim, Hee Sun [KHNP Radiation Health Institute, Korea Hydro & Nuclear Power Co, Seoul (Korea, Republic of); Pyo, Suhkneung [College of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do (Korea, Republic of); Yang, Kwang Hee, E-mail: kwangheey@khnp.co.kr [KHNP Radiation Health Institute, Korea Hydro & Nuclear Power Co, Seoul (Korea, Republic of)

2016-04-01

Purpose: To determine how low-dose ionizing radiation (LDIR) regulates B lympho-proliferation and its molecular mechanism related with Ikaros, transcription factor. Methods and Materials: Splenocytes and IM-9 cells were uniformly irradiated with various doses of a {sup 137}Cs γ-source, and cell proliferation was analyzed. To determine the LDIR-specific phosphorylation of Ikaros, immunoprecipitation and Western blot analysis were performed. To investigate the physiologic function of LDIR-mediatied Ikaros phosphorylation, Ikaros mutants at phosphorylation sites were generated, and cell cycle analysis was performed. Results: First, we found that LDIR enhances B lymphoblast proliferation in an Ikaros-dependent manner. Moreover, we found that LDIR elevates the phosphorylation level of Ikaros protein. Interestingly, we showed that CK2 and AKT are involved in LDIR-induced Ikaros phosphorylation and capable of regulating DNA binding activity of Ikaros via specific phosphorylation. Finally, we identified LDIR-specific Ikaros phosphorylation sites at S391/S393 and showed that the Ikaros phosphorylations at these sites control Ikaros's ability to regulate G1/S cell cycle progression. Conclusion: Low-dose ionizing radiation specifically phosphorylates Ikaros protein at Ser 391/393 residues to regulate cell cycle progression in B lymphoblast.

Site-Specific Phosphorylation of Ikaros Induced by Low-Dose Ionizing Radiation Regulates Cell Cycle Progression of B Lymphoblast Through CK2 and AKT Activation.

Science.gov (United States)

Cho, Seong-Jun; Kang, Hana; Kim, Min Young; Lee, Jung Eun; Kim, Sung Jin; Nam, Seon Young; Kim, Ji Young; Kim, Hee Sun; Pyo, Suhkneung; Yang, Kwang Hee

2016-04-01

To determine how low-dose ionizing radiation (LDIR) regulates B lympho-proliferation and its molecular mechanism related with Ikaros, transcription factor. Splenocytes and IM-9 cells were uniformly irradiated with various doses of a (137)Cs γ-source, and cell proliferation was analyzed. To determine the LDIR-specific phosphorylation of Ikaros, immunoprecipitation and Western blot analysis were performed. To investigate the physiologic function of LDIR-mediatied Ikaros phosphorylation, Ikaros mutants at phosphorylation sites were generated, and cell cycle analysis was performed. First, we found that LDIR enhances B lymphoblast proliferation in an Ikaros-dependent manner. Moreover, we found that LDIR elevates the phosphorylation level of Ikaros protein. Interestingly, we showed that CK2 and AKT are involved in LDIR-induced Ikaros phosphorylation and capable of regulating DNA binding activity of Ikaros via specific phosphorylation. Finally, we identified LDIR-specific Ikaros phosphorylation sites at S391/S393 and showed that the Ikaros phosphorylations at these sites control Ikaros's ability to regulate G1/S cell cycle progression. Low-dose ionizing radiation specifically phosphorylates Ikaros protein at Ser 391/393 residues to regulate cell cycle progression in B lymphoblast. Copyright © 2016 Elsevier Inc. All rights reserved.

Site-Specific Phosphorylation of Ikaros Induced by Low-Dose Ionizing Radiation Regulates Cell Cycle Progression of B Lymphoblast Through CK2 and AKT Activation

International Nuclear Information System (INIS)

Cho, Seong-Jun; Kang, Hana; Kim, Min Young; Lee, Jung Eun; Kim, Sung Jin; Nam, Seon Young; Kim, Ji Young; Kim, Hee Sun; Pyo, Suhkneung; Yang, Kwang Hee

2016-01-01

Purpose: To determine how low-dose ionizing radiation (LDIR) regulates B lympho-proliferation and its molecular mechanism related with Ikaros, transcription factor. Methods and Materials: Splenocytes and IM-9 cells were uniformly irradiated with various doses of a "1"3"7Cs γ-source, and cell proliferation was analyzed. To determine the LDIR-specific phosphorylation of Ikaros, immunoprecipitation and Western blot analysis were performed. To investigate the physiologic function of LDIR-mediatied Ikaros phosphorylation, Ikaros mutants at phosphorylation sites were generated, and cell cycle analysis was performed. Results: First, we found that LDIR enhances B lymphoblast proliferation in an Ikaros-dependent manner. Moreover, we found that LDIR elevates the phosphorylation level of Ikaros protein. Interestingly, we showed that CK2 and AKT are involved in LDIR-induced Ikaros phosphorylation and capable of regulating DNA binding activity of Ikaros via specific phosphorylation. Finally, we identified LDIR-specific Ikaros phosphorylation sites at S391/S393 and showed that the Ikaros phosphorylations at these sites control Ikaros's ability to regulate G1/S cell cycle progression. Conclusion: Low-dose ionizing radiation specifically phosphorylates Ikaros protein at Ser 391/393 residues to regulate cell cycle progression in B lymphoblast.

Overexpression of cell cycle regulator CDCA3 promotes oral cancer progression by enhancing cell proliferation with prevention of G1 phase arrest

International Nuclear Information System (INIS)

Uchida, Fumihiko; Uzawa, Katsuhiro; Kasamatsu, Atsushi; Takatori, Hiroaki; Sakamoto, Yosuke; Ogawara, Katsunori; Shiiba, Masashi; Tanzawa, Hideki; Bukawa, Hiroki

2012-01-01

Cell division cycle associated 3 (CDCA3), part of the Skp1-cullin-F-box (SCF) ubiquitin ligase, refers to a trigger of mitotic entry and mediates destruction of the mitosis inhibitory kinase. Little is known about the relevance of CDCA3 to human malignancy including oral squamous cell carcinoma (OSCC). We aimed to characterize the expression state and function of CDCA3 in OSCC. We evaluated CDCA3 mRNA and protein expression in both OSCC-derived cell lines and primary OSCCs and performed functional analyses of CDCA3 in OSCC-derived cells using the shRNA system. The CDCA3 expression at both the mRNA and protein levels was frequently up-regulated in all cell lines examined and primary tumors (mRNA, 51/69, 74 %; protein, 79/95, 83 %) compared to normal controls (p < 0.001). In contrast, no significant level of CDCA3 protein expression was seen in oral premalignant lesions (OPLs) (n = 20) compared with the expression in OSCCs. Among the clinical variables analyzed, the CDCA3 expression status was closely related to tumor size (p < 0.05). In addition, suppression of CDCA3 expression with shRNA significantly (p < 0.05) inhibited cellular proliferation compared with the control cells by arresting cell-cycle progression at the G1 phase. Further, there was up-regulation of the cyclin-dependent kinase inhibitors (p21 Cip1 , p27 Kip1 , p15 INK4B , and p16 INK4A ) in the knockdown cells. The current results showed that overexpression of CDCA3 occurs frequently during oral carcinogenesis and this overexpression might be associated closely with progression of OSCCs by preventing the arrest of cell-cycle progression at the G1 phase via decreased expression of the cyclin-dependent kinase inhibitors

Emissions from photovoltaic life cycles

NARCIS (Netherlands)

Fthenakis, V.M.; Kim, H.C.; Alsema, E.A.|info:eu-repo/dai/nl/073416258

2008-01-01

Photovoltaic (PV) technologies have shown remarkable progress recently in terms of annual production capacity and life cycle environmental performances, which necessitate timely updates of environmental indicators. Based on PV production data of 2004–2006, this study presents the life-cycle

Progress and status of the international project on innovative nuclear reactors and fuel cycles (INPRO) - 5182

International Nuclear Information System (INIS)

Ponomarev, A.; Fesenko, G.; Grigoriev, F.G.; Korinny, A.; Phillips, J.R.; Rho, K.

2015-01-01

The IAEA's International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO) was established in 2000 through IAEA General Conference resolution. INPRO cooperates with Member States to ensure that sustainable nuclear energy is available to help meet the energy needs of the 21. century. INPRO membership has grown to 41 members and 16 observers. The paper presents the current prospectus of the INPRO programme and details the most recent achievements in the following 7 projects: 1) the GAINS project (Global Architecture of Innovative Nuclear Energy Systems with thermal and fast reactors and a closed nuclear fuel cycle); 2) the SYNERGIES project applies and amends the analytical framework developed in GAINS project to examine more specifically the various forms of regional collaboration among nuclear energy suppliers and users; 3) the KIND project (Key Indicators for Innovative Nuclear Energy Systems) has the objective of developing guidance on the evaluation on innovative nuclear technologies; 4) the ROADMAPS project addresses several possible stages toward nuclear energy sustainability; 5) the RISC project aims at demonstrating that the evolution of safety requirements and technical innovations provide continual progress towards the avoidance of evacuation measures outside NPP sites in case of severe accidents; 6) the FANES project has the objective of carrying out feasibility analyses of advanced and innovative fuels for different reactor systems; and 7) the WIRAF project aims at identifying problematic waste from innovative reactor designs and corresponding nuclear fuel cycles

Nuclear fuel cycle under progressing preparation of its systemisation

International Nuclear Information System (INIS)

Anon.

2001-01-01

Trends of nuclear development in Japan show more remarkable advancements in 2000, such as new addition of nuclear power plant, nuclear fuel cycling business, and so on. Based on an instruction of the criticality accident in JCO formed on September, 1999, government made efforts on revision of the law on regulation of nuclear reactor and so forth and establishment of a law on protection of nuclear accident as sooner, to enforce nuclear safety management and nuclear accident protective countermeasure. On the other hand, the nuclear industry field develops some new actions such as establishment of Nuclear Safety Network (NSnet)', mutual evaluation of nuclear-relative works (pier review), and so forth. And, on the high level radioactive wastes disposal of the most important subject remained in nuclear development, the Nuclear Waste Management Organization of Japan' of its main business body was established on October, 1999 together with establishment of the new law, to begin a business for embodiment of the last disposal aiming at 2030s to 2040s. On the same October, the Japan Nuclear Fuel Limited. concluded a safety agreement on premise of full-dress transportation of the used fuels to the Rokkasho Reprocessing Plant in Aomori prefecture with local government, to begin their transportation from every electric company since its year end. Here were described on development of the nuclear fuel cycling business in Japan, establishment of nuclear fuel cycling, disposal on the high level radioactive wastes, R and D on geological disposal of the high level radioactive wastes, establishment on cycle back-end of nuclear fuels, and full-dressing of nuclear fuel cycling. (G.K.)

Histone deacetylase inhibitors SAHA and sodium butyrate block G1-to-S cell cycle progression in neurosphere formation by adult subventricular cells

Directory of Open Access Journals (Sweden)

Doughty Martin L

2011-05-01

Full Text Available Abstract Background Histone deacetylases (HDACs are enzymes that modulate gene expression and cellular processes by deacetylating histones and non-histone proteins. While small molecule inhibitors of HDAC activity (HDACi are used clinically in the treatment of cancer, pre-clinical treatment models suggest they also exert neuroprotective effects and stimulate neurogenesis in neuropathological conditions. However, the direct effects of HDACi on cell cycle progression and proliferation, two properties required for continued neurogenesis, have not been fully characterized in adult neural stem cells (NSCs. In this study, we examined the effects of two broad class I and class II HDACi on adult mouse NSCs, the hydroxamate-based HDACi suberoylanilide hydroxamic acid (vorinostat, SAHA and the short chain fatty acid HDACi sodium butyrate. Results We show that both HDACi suppress the formation of neurospheres by adult mouse NSCs grown in proliferation culture conditions in vitro. DNA synthesis is significantly inhibited in adult mouse NSCs exposed to either SAHA or sodium butyrate and inhibition is associated with an arrest in the G1 phase of the cell cycle. HDACi exposure also resulted in transcriptional changes in adult mouse NSCs. Cdk inhibitor genes p21 and p27 transcript levels are increased and associated with elevated H3K9 acetylation levels at proximal promoter regions of p21 and p27. mRNA levels for notch effector Hes genes and Spry-box stem cell transcription factors are downregulated, whereas pro-neural transcription factors Neurog1 and Neurod1 are upregulated. Lastly, we show HDAC inhibition under proliferation culture conditions leads to long-term changes in cell fate in adult mouse NSCs induced to differentiate in vitro. Conclusion SAHA and sodium butyrate directly regulate cdk inhibitor transcription to control cell cycle progression in adult mouse NSCs. HDAC inhibition results in G1 arrest in adult mouse NSCs and transcriptional changes

Potential Inhibitors for Isocitrate Lyase of Mycobacterium tuberculosis and Non-M. tuberculosis: A Summary

Directory of Open Access Journals (Sweden)

Yie-Vern Lee

2015-01-01

Full Text Available Isocitrate lyase (ICL is the first enzyme involved in glyoxylate cycle. Many plants and microorganisms are relying on glyoxylate cycle enzymes to survive upon downregulation of tricarboxylic acid cycle (TCA cycle, especially Mycobacterium tuberculosis (MTB. In fact, ICL is a potential drug target for MTB in dormancy. With the urge for new antitubercular drug to overcome tuberculosis treat such as multidrug resistant strain and HIV-coinfection, the pace of drug discovery has to be increased. There are many approaches to discovering potential inhibitor for MTB ICL and we hereby review the updated list of them. The potential inhibitors can be either a natural compound or synthetic compound. Moreover, these compounds are not necessary to be discovered only from MTB ICL, as it can also be discovered by a non-MTB ICL. Our review is categorized into four sections, namely, (a MTB ICL with natural compounds; (b MTB ICL with synthetic compounds; (c non-MTB ICL with natural compounds; and (d non-MTB ICL with synthetic compounds. Each of the approaches is capable of overcoming different challenges of inhibitor discovery. We hope that this paper will benefit the discovery of better inhibitor for ICL.

An incomplete TCA cycle increases survival of Salmonella Typhimurium during infection of resting and activated murine macrophages.

Science.gov (United States)

Bowden, Steven D; Ramachandran, Vinoy K; Knudsen, Gitte M; Hinton, Jay C D; Thompson, Arthur

2010-11-08

In comparison to the comprehensive analyses performed on virulence gene expression, regulation and action, the intracellular metabolism of Salmonella during infection is a relatively under-studied area. We investigated the role of the tricarboxylic acid (TCA) cycle in the intracellular replication of Salmonella Typhimurium in resting and activated macrophages, epithelial cells, and during infection of mice. We constructed deletion mutations of 5 TCA cycle genes in S. Typhimurium including gltA, mdh, sdhCDAB, sucAB, and sucCD. We found that the mutants exhibited increased net intracellular replication in resting and activated murine macrophages compared to the wild-type. In contrast, an epithelial cell infection model showed that the S. Typhimurium ΔsucCD and ΔgltA strains had reduced net intracellular replication compared to the wild-type. The glyoxylate shunt was not responsible for the net increased replication of the TCA cycle mutants within resting macrophages. We also confirmed that, in a murine infection model, the S. Typhimurium ΔsucAB and ΔsucCD strains are attenuated for virulence. Our results suggest that disruption of the TCA cycle increases the ability of S. Typhimurium to survive within resting and activated murine macrophages. In contrast, epithelial cells are non-phagocytic cells and unlike macrophages cannot mount an oxidative and nitrosative defence response against pathogens; our results show that in HeLa cells the S. Typhimurium TCA cycle mutant strains show reduced or no change in intracellular levels compared to the wild-type. The attenuation of the S. Typhimurium ΔsucAB and ΔsucCD mutants in mice, compared to their increased net intracellular replication in resting and activated macrophages suggest that Salmonella may encounter environments within the host where a complete TCA cycle is advantageous.

Research Establishment progress report 1978 - uranium fuel cycle

International Nuclear Information System (INIS)

1978-12-01

A report of research programs continuing in the following areas is presented: mining and treatment of uranium ores, uranium enrichment, waste treatment, reprocessing and the uranium fuel cycle. Staff responsible for each project are indicated

Synthetic Progress toward Azadirachtins. 2. Enantio- and Diastereoselective Synthesis of the Right-Wing Fragment of 11-epi-Azadirachtin I.

Science.gov (United States)

Tan, Ceheng; Chen, Wei; Mu, Xinpeng; Chen, Qi; Gong, Jianxian; Luo, Tuoping; Yang, Zhen

2015-05-15

A stereoselective three-component coupling reaction of allylzinc bromide, silyl glyoxylate, and a β-lactone has been developed. This has been successfully applied to the enantio- and diastereoselective synthesis of the fully functionalized furopyran moiety of azadirachtins.

Facultative methanotrophy: false leads, true results, and suggestions for future research.

Science.gov (United States)

Semrau, Jeremy D; DiSpirito, Alan A; Vuilleumier, Stéphane

2011-10-01

Methanotrophs are a group of phylogenetically diverse microorganisms characterized by their ability to utilize methane as their sole source of carbon and energy. Early studies suggested that growth on methane could be stimulated with the addition of some small organic acids, but initial efforts to find facultative methanotrophs, i.e., methanotrophs able to utilize compounds with carbon-carbon bonds as sole growth substrates were inconclusive. Recently, however, facultative methanotrophs in the genera Methylocella, Methylocapsa, and Methylocystis have been reported that can grow on acetate, as well as on larger organic acids or ethanol for some species. All identified facultative methanotrophs group within the Alphaproteobacteria and utilize the serine cycle for carbon assimilation from formaldehyde. It is possible that facultative methanotrophs are able to convert acetate into intermediates of the serine cycle (e.g. malate and glyoxylate), because a variety of acetate assimilation pathways convert acetate into these compounds (e.g. the glyoxylate shunt of the tricarboxylic acid cycle, the ethylmalonyl-CoA pathway, the citramalate cycle, and the methylaspartate cycle). In this review, we summarize the history of facultative methanotrophy, describe scenarios for the basis of facultative methanotrophy, and pose several topics for future research in this area. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Effects of 3-AB on PARP expression of Hela cells and apoptosis and cell cycle progression of Hela cells after X-rays irradiation

International Nuclear Information System (INIS)

Du Xiang; Zhao Hongguang; Guo Wei; Gong Shouliang; Wang Wen

2007-01-01

Objective: To study the changes of apoptosis and cell cycle progression of Hela cells after the poly (ADP- ribose) polymerase (PARP) was inhibited by its inhibitor 3-aminobenzamid (3-AB) and the mechanisms of PARP interaction with Hela cells damaged by irradiation. Methods: Hela cell line was used. Flow cytometry (FCM) was used to examine the PARP expression of control and 3 AB groups at 0, 2, 4, 8, 12 h alter administration with 5 mmol·L -1 3-AB. The percentage of apoptotic cells and cell cycle progression ol control, irradiation, 3-AB plus irradiation groups were measured with FCM at 2, 8, 12, 24 h after exposure to 2 Gy irradiation following administration with 5 mmol·L -1 3-AB. Results: The percentage of Hela cells with positive expression of PARP protein decreased after administration with 3-AB and there was significant difference between 3-AB plus irradiation group and control group (P 2 cells in the 3-AB plus irradiation group were lower than those in the irradiation group (P 2 arrest induced by irradiation. (authors)

Cell cycle checkpoints: reversible when possible, irreversible when needed

NARCIS (Netherlands)

Krenning, L.

2015-01-01

Cell cycle checkpoints are reversible in nature, and can prevent progression into the next cell cycle phase if needed. In the case of DNA damage, cells can prevent progression from G1 into S phase, and from G2 into mitosis in the presence of DNA double strand breaks. Following DNA repair, these

Connecting the nucleolus to the cell cycle and human disease.

Science.gov (United States)

Tsai, Robert Y L; Pederson, Thoru

2014-08-01

Long known as the center of ribosome synthesis, the nucleolus is connected to cell cycle regulation in more subtle ways. One is a surveillance system that reacts promptly when rRNA synthesis or processing is impaired, halting cell cycle progression. Conversely, the nucleolus also acts as a first-responder to growth-related stress signals. Here we review emerging concepts on how these "infraribosomal" links between the nucleolus and cell cycle progression operate in both forward and reverse gears. We offer perspectives on how new cancer therapeutic designs that target this infraribosomal mode of cell growth control may shape future clinical progress. © FASEB.

Closing the fuel cycle

International Nuclear Information System (INIS)

Aycoberry, C.; Rougeau, J.P.

1987-01-01

The progressive implementation of some key nuclear fuel cycle capecities in a country corresponds to a strategy for the acquisition of an independant energy source, France, Japan, and some European countries are engaged in such strategic programs. In France, COGEMA, the nuclear fuel company, has now completed the industrial demonstration of the closed fuel cycle. Its experience covers every step of the front-end and of the back-end: transportation of spent fuels, storage, reprocessing, wastes conditioning. The La Hague reprocessing plant smooth operation, as well as the large investment program under active progress can testify of full mastering of this industry. Together with other French and European companies, COGEMA is engaged in the recycling industry, both for uranium through conversion of uranyl nitrate for its further reeichment, and for plutonium through MOX fuel fabrication. Reprocessing and recycling offer the optimum solution for a complete, economic, safe and future-oriented fuel cycle, hence contributing to the necessary development of nuclear energy. (author)

The KRAB Zinc Finger Protein Roma/Zfp157 Is a Critical Regulator of Cell-Cycle Progression and Genomic Stability

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Teresa L.F. Ho

2016-04-01

Full Text Available Regulation of DNA replication and cell division is essential for tissue growth and maintenance of genomic integrity and is particularly important in tissues that undergo continuous regeneration such as mammary glands. We have previously shown that disruption of the KRAB-domain zinc finger protein Roma/Zfp157 results in hyperproliferation of mammary epithelial cells (MECs during pregnancy. Here, we delineate the mechanism by which Roma engenders this phenotype. Ablation of Roma in MECs leads to unscheduled proliferation, replication stress, DNA damage, and genomic instability. Furthermore, mouse embryonic fibroblasts (MEFs depleted for Roma exhibit downregulation of p21Cip1 and geminin and have accelerated replication fork velocities, which is accompanied by a high rate of mitotic errors and polyploidy. In contrast, overexpression of Roma in MECs halts cell-cycle progression, whereas siRNA-mediated p21Cip1 knockdown ameliorates, in part, this phenotype. Thus, Roma is an essential regulator of the cell cycle and is required to maintain genomic stability.

The effect of post-wash total progressive motile sperm count and semen volume on pregnancy outcomes in intrauterine insemination cycles: a retrospective study.

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Ok, Elvan Koyun; Doğan, Omer Erbil; Okyay, Recep Emre; Gülekli, Bülent

2013-01-01

The purpose of this study was to determine the impact of post-wash total progressive motile sperm count (TPMSC) and semen volume on pregnancy outcomes in intrauterine insemination (IUI) cycles. The retrospective study included a total of 156 cycles (141 couples) and was performed in our center over a 24-month period. The semen parameters were recorded for each man and each insemination. The semen samples were re-evaluated after the preparation process. Post-wash TPMSC values were divided into four groups; Group 1: 10×10(6). Post-wash inseminated semen volume was divided into three groups; Group 1: 0.3 mL; Group 2: 0.4 mL; Group 3: 0.5 mL. The effect of post-wash total progressive motile sperm and semen volume on pregnancy outcomes was evaluated. The pregnancy rates per cycle and per couple were 27.56% and 30.49%, respectively. There was not a significant relationship between the inseminated semen volume and pregnancy rate (p>0.05). However, a significant linear-by-linear association was documented between the TPMSC and pregnancy rate (p=0.042). Our findings suggest that the post-wash inseminated semen volume should be between 0.3-0.5 mL. An average post-wash total motile sperm count of 10×10(6) may be a useful threshold value for IUI success, but more studies are needed to determine a cut-off value for TPMSC.

Restoration of microRNA‑218 increases cellular chemosensitivity to cervical cancer by inhibiting cell‑cycle progression.

Science.gov (United States)

Dong, Ruofan; Qiu, Haifeng; Du, Guiqiang; Wang, Yuan; Yu, Jinjin; Mao, Caiping

2014-12-01

We previously reported frequent loss of microRNA‑218 (miR‑218) in human cervical cancer, which was associated with tumor progression and poor prognosis. In this study, we investigated whether restoration of the miR‑218 level is a valid strategy for the treatment of cervical cancer. The expression of miR‑218 in cervical cancer samples and cell lines was quantified by reverse transcription TaqMan quantitative (RT‑q)PCR. Overexpression of miR‑218 was achieved by both transient and stable transfection, using a miR‑218 mimic and a miR‑218‑expressing plasmid, respectively. Alterations in cellular proliferation and cell‑cycle progression were measured by the MTT assay and flow cytometry analysis. Nude mice bearing SiHa xenografts were used to investigate the functions of miR‑218 and carboplatin on tumor growth and weight. The expression of cycle‑related proteins was detected by western blotting and immunohistochemical staining. In vitro, miR‑218 significantly inhibited cellular growth in all four cell lines tested (P=0.021 for CaSki, P=0.009 for HeLa, P=0.016 for SiHa, and P=0.029 for C33A). Overexpression of miR‑218 induced G1 phase arrest and reduced expression of cyclin D1 and CDK4. In vivo, restoration of miR‑218 notably inhibited tumor growth and decreased tumor weight. In primary cultured samples, tumors with high levels of miR‑218 were more sensitive to carboplatin (R2=0.3319, P=0.0026); consistently, miR‑218 overexpression suppressed tumor growth, induced cell‑cycle arrest, and reduced the cyclin D1 level. Based on these and previous results, we conclude that restoration of the miR‑218 level inhibits the growth of cervical cancer cells both in vitro and in vivo; furthermore, overexpression of miR‑218 sensitizes cervical cancer cells to carboplatin. Our findings suggest a novel therapy for cervical cancer based on miR‑218, especially in patients with reduced levels of miR‑218.

Effect of hyperthermia and radiation on the cell cycle progression of HeLa cells

International Nuclear Information System (INIS)

Kubota, Nobuo

1982-01-01

The effect of hyperthermia and irradiation on cytokinetics was studied using exponentially growing HeLa cells. To determine the effect of heat and/or radiation on the cell cycle progression, the changes in the DNA distribution of the cell population after time intervals after treatment were studied. The cellular DNA content of the cell population was measured by flow cytometry. The results obtained were as follows: 1. Compared with the control, the cellular DNA content distribution of HeLa cells treated with 43 0 C for 20 min and 60 min showed cell accumulation in S and G 2 M phases 8 hours after treatment. 2. Hyperthermic treatment at 45 0 C for 20 min caused cells to accumulate in S phase in the first 4 hours and G 2 M phase after 8 to 14.5 hours, whereas heat treatment at 45 0 C for 60 min caused cells to accumulate in G 2 M phase after 24 hours. 3. Irradiation of exponentially growing cells induced a block in the progress from G 2 M to G 1 phase. 4. Dose survival curves of HeLa cells with and without postirradiation thermal treatment (43 0 C, 60 min) showed significant enhancement of radiosensitivity by hyperthermia. 5. The sequential treatment, i.e. 5 Gy irradiation followed immediately by heat treatment at 43 0 C for 60 min, caused more cells to accumulate in G 2 M phase after 24 and 48 hours, as compared with 5 Gy irradiation alone. (author)

Progesterone receptor blockade in human breast cancer cells decreases cell cycle progression through G2/M by repressing G2/M genes

OpenAIRE

Clare, Susan E.; Gupta, Akash; Choi, MiRan; Ranjan, Manish; Lee, Oukseub; Wang, Jun; Ivancic, David Z.; Kim, J. Julie; Khan, Seema A.

2016-01-01

Background The synthesis of specific, potent progesterone antagonists adds potential agents to the breast cancer prevention and treatment armamentarium. The identification of individuals who will benefit from these agents will be a critical factor for their clinical success. Methods We utilized telapristone acetate (TPA; CDB-4124) to understand the effects of progesterone receptor (PR) blockade on proliferation, apoptosis, promoter binding, cell cycle progression, and gene expression. We then...

Cell Cycle Regulation of Stem Cells by MicroRNAs.

Science.gov (United States)

Mens, Michelle M J; Ghanbari, Mohsen

2018-06-01

MicroRNAs (miRNAs) are a class of small non-coding RNA molecules involved in the regulation of gene expression. They are involved in the fine-tuning of fundamental biological processes such as proliferation, differentiation, survival and apoptosis in many cell types. Emerging evidence suggests that miRNAs regulate critical pathways involved in stem cell function. Several miRNAs have been suggested to target transcripts that directly or indirectly coordinate the cell cycle progression of stem cells. Moreover, previous studies have shown that altered expression levels of miRNAs can contribute to pathological conditions, such as cancer, due to the loss of cell cycle regulation. However, the precise mechanism underlying miRNA-mediated regulation of cell cycle in stem cells is still incompletely understood. In this review, we discuss current knowledge of miRNAs regulatory role in cell cycle progression of stem cells. We describe how specific miRNAs may control cell cycle associated molecules and checkpoints in embryonic, somatic and cancer stem cells. We further outline how these miRNAs could be regulated to influence cell cycle progression in stem cells as a potential clinical application.

Integrated Analysis of the Effects of Cold and Dehydration on Rice Metabolites, Phytohormones, and Gene Transcripts1[W][OPEN

Science.gov (United States)

Maruyama, Kyonoshin; Urano, Kaoru; Yoshiwara, Kyouko; Morishita, Yoshihiko; Sakurai, Nozomu; Suzuki, Hideyuki; Kojima, Mikiko; Sakakibara, Hitoshi; Shibata, Daisuke; Saito, Kazuki; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

2014-01-01

Correlations between gene expression and metabolite/phytohormone levels under abiotic stress conditions have been reported for Arabidopsis (Arabidopsis thaliana). However, little is known about these correlations in rice (Oryza sativa ‘Nipponbare’), despite its importance as a model monocot. We performed an integrated analysis to clarify the relationships among cold- and dehydration-responsive metabolites, phytohormones, and gene transcription in rice. An integrated analysis of metabolites and gene expression indicated that several genes encoding enzymes involved in starch degradation, sucrose metabolism, and the glyoxylate cycle are up-regulated in rice plants exposed to cold or dehydration and that these changes are correlated with the accumulation of glucose (Glc), fructose, and sucrose. In particular, high expression levels of genes encoding isocitrate lyase and malate synthase in the glyoxylate cycle correlate with increased Glc levels in rice, but not in Arabidopsis, under dehydration conditions, indicating that the regulation of the glyoxylate cycle may be involved in Glc accumulation under dehydration conditions in rice but not Arabidopsis. An integrated analysis of phytohormones and gene transcripts revealed an inverse relationship between abscisic acid (ABA) signaling and cytokinin (CK) signaling under cold and dehydration stresses; these stresses increase ABA signaling and decrease CK signaling. High levels of Oryza sativa 9-cis-epoxycarotenoid dioxygenase transcripts correlate with ABA accumulation, and low levels of Cytochrome P450 (CYP) 735A transcripts correlate with decreased levels of a CK precursor in rice. This reduced expression of CYP735As occurs in rice but not Arabidopsis. Therefore, transcriptional regulation of CYP735As might be involved in regulating CK levels under cold and dehydration conditions in rice but not Arabidopsis. PMID:24515831

Effects of valproic acid and pioglitazone on cell cycle progression and proliferation of T-cell acute lymphoblastic leukemia Jurkat cells

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Marie Saghaeian Jazi

2016-07-01

Full Text Available Objective(s: T-cell acute lymphoblastic leukemia (T-ALL is an aggressive hematologic malignant tumor. Administration of chemical compounds influencing apoptosis and T cell development has been discussed as promising novel therapeutic strategies. Valproic acid (VPA as a recently emerged anti-neoplastic histone deacetylase (HDAC inhibitor and pioglitazone (PGZ as a high-affinity peroxisome proliferator-activated receptor-gamma (PPARγ agonist have been shown to induce apoptosis and cell cycle arrest in different studies. Here, we aimed to investigate the underlying molecular mechanisms involved in anti-proliferative effects of these compounds on human Jurkat cells. Materials and Methods: Treated cells were evaluated for cell cycle progression and apoptosis using flowcytometry and MTT viability assay. Real-time RT-PCR was carried out to measure the alterations in key genes associated with cell death and cell cycle arrest. Results: Our findings illustrated that both VPA and PGZ can inhibit Jurkat E6.1 cells in vitro after   24 hr; however, PGZ 400 μM presents the most anti-proliferative effect. Interestingly, treated cells have been arrested in G2/M with deregulated cell division cycle 25A (Cdc25A phosphatase and cyclin-dependent kinase inhibitor 1B (CDKN1B or p27 expression. Expression of cyclin D1 gene was inhibited when DNA synthesis entry was declined. Cell cycle deregulation in PGZ and VPA-exposed cells generated an increase in the proportion of aneuploid cell population, which has not reported before. Conclusion: These findings define that anti-proliferative effects of PGZ and VPA on Jurkat cell line are mediated by cell cycle deregulation. Thus, we suggest PGZ and VPA may relieve potential therapeutic application against apoptosis-resistant malignancies.

Tousled-like kinase-dependent phosphorylation of Rad9 plays a role in cell cycle progression and G2/M checkpoint exit.

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Ryan Kelly

Full Text Available Genomic integrity is preserved by checkpoints, which act to delay cell cycle progression in the presence of DNA damage or replication stress. The heterotrimeric Rad9-Rad1-Hus1 (9-1-1 complex is a PCNA-like clamp that is loaded onto DNA at structures resulting from damage and is important for initiating and maintaining the checkpoint response. Rad9 possesses a C-terminal tail that is phosphorylated constitutively and in response to cell cycle position and DNA damage. Previous studies have identified tousled-like kinase 1 (TLK1 as a kinase that may modify Rad9. Here we show that Rad9 is phosphorylated in a TLK-dependent manner in vitro and in vivo, and that T355 within the C-terminal tail is the primary targeted residue. Phosphorylation of Rad9 at T355 is quickly reduced upon exposure to ionizing radiation before returning to baseline later in the damage response. We also show that TLK1 and Rad9 interact constitutively, and that this interaction is enhanced in chromatin-bound Rad9 at later stages of the damage response. Furthermore, we demonstrate via siRNA-mediated depletion that TLK1 is required for progression through S-phase in normally cycling cells, and that cells lacking TLK1 display a prolonged G2/M arrest upon exposure to ionizing radiation, a phenotype that is mimicked by over-expression of a Rad9-T355A mutant. Given that TLK1 has previously been shown to be transiently inactivated upon phosphorylation by Chk1 in response to DNA damage, we propose that TLK1 and Chk1 act in concert to modulate the phosphorylation status of Rad9, which in turn serves to regulate the DNA damage response.

Feasibility and safety of extended adjuvant temozolomide beyond six cycles for patients with glioblastoma.

Science.gov (United States)

Hsieh, S Yp; Chan, D Tm; Kam, M Km; Loong, H Hf; Tsang, W K; Poon, D Mc; Ng, S Cp; Poon, W S

2017-12-01

Temozolomide is the first chemotherapeutic agent proven effective for patients with newly diagnosed glioblastoma. The drug is well tolerated for its low toxicity. The current standard practice is concomitant chemoradiotherapy for 6 weeks followed by 6 cycles of adjuvant temozolomide. Some Caucasian studies have suggested that patients might benefit from extended adjuvant cycles of temozolomide (>6 cycles) to lengthen both progression-free survival and overall survival. In the present study, we compared differences in survival and toxicity profile between patients who received conventional 6-cycle temozolomide and those who received more than 6 cycles of temozolomide. Patients with newly diagnosed glioblastoma without progressive disease and completed concomitant chemoradiotherapy during a 4-year period were studied. Progression-free survival was compared using Kaplan-Meier survival curves. t Test, U test, and correlation were chosen accordingly to examine the impact of age, extent of resection, MGMT promoter methylation status and adjuvant cycles on progression-free survival. For factors with a P value of cycles of temozolomide (n=7) and 43.4 months for those who received more than 6 cycles (n=7) [P=0.007, log-rank test]. Two patients in the former group and one in the latter group encountered grade 1 toxicity and recovered following dose adjustment. Cycles of adjuvant temozolomide were correlated with progression-free survival (P=0.016, hazard ratio=0.68). Extended cycles of temozolomide are safe and feasible for Chinese patients with disease responsive to temozolomide.

Dose-rate effect of adaptive response of apoptosis and cell cycle progression induced by low-dose ionizing radiation in EL-4 lymphoma cells in vitro

International Nuclear Information System (INIS)

Liu Shuchun; Lu Zhe; Li Yanbo; Kang Shunai; Gong Shouliang; Zhao Wenju

2008-01-01

Objective: To observe the dose-rate effect of adaptive response of apoptosis and cell cycle progression induced by low-dose ionizing radiation in EL-4 lymphoma cells in vitro in order to reveal the possible mechanism of biological effect and adaptive response induced by low dose radiation. Methods: The experiment was divided into D2 (challenging dose), D1 (inductive dose) + D2 and sham-irradiation groups. EL-4 lymphoma cells were irradiated with D1 (75 mGy, 6.25-200.00 mGy·mm -1 ) and D2(1.5 Gy, 287 mGy·min -1 ), the time interval between D1 and D2 was 6 h. The percentage of apoptosis and each cell cycle phase were measured with flow cytometry. Results: When the dose rates of D1 were 6.25-50.00 mGy·min -1 , the percentages of apoptosis in the D1 + D2 group were significantly lower than those in the D2 group (P 0 /G 1 phase cells decreased significantly (P -1 , D2 is 1.5 Gy (287 mGy·min -1 ), and the time interval between D1 and D2 is 6 h, the adaptive response of apoptosis and cell cycle progression in EL-4 lymphoma cells in vitro could be induced. (authors)

Animal Models for Studying the In Vivo Functions of Cell Cycle CDKs.

Science.gov (United States)

Risal, Sanjiv; Adhikari, Deepak; Liu, Kui

2016-01-01

Multiple Cdks (Cdk4, Cdk6, and Cdk2) and a mitotic Cdk (Cdk1) are involved in cell cycle progression in mammals. Cyclins, Cdk inhibitors, and phosphorylations (both activating and inhibitory) at different cellular levels tightly modulate the activities of these kinases. Based on the results of biochemical studies, it was long believed that different Cdks functioned at specific stages during cell cycle progression. However, deletion of all three interphase Cdks in mice affected cell cycle entry and progression only in certain specialized cells such as hematopoietic cells, beta cells of the pancreas, pituitary lactotrophs, and cardiomyocytes. These genetic experiments challenged the prevailing biochemical model and established that Cdks function in a cell-specific, but not a stage-specific, manner during cell cycle entry and the progression of mitosis. Recent in vivo studies have further established that Cdk1 is the only Cdk that is both essential and sufficient for driving the resumption of meiosis during mouse oocyte maturation. These genetic studies suggest a minimal-essential cell cycle model in which Cdk1 is the central regulator of cell cycle progression. Cdk1 can compensate for the loss of the interphase Cdks by forming active complexes with A-, B-, E-, and D-type Cyclins in a stepwise manner. Thus, Cdk1 plays an essential role in both mitosis and meiosis in mammals, whereas interphase Cdks are dispensable.

Depletion of Plasmodium berghei plasmoredoxin reveals a non-essential role for life cycle progression of the malaria parasite.

Science.gov (United States)

Buchholz, Kathrin; Rahlfs, Stefan; Schirmer, R Heiner; Becker, Katja; Matuschewski, Kai

2008-06-25

Proliferation of the pathogenic Plasmodium asexual blood stages in host erythrocytes requires an exquisite capacity to protect the malaria parasite against oxidative stress. This function is achieved by a complex antioxidant defence system composed of redox-active proteins and low MW antioxidants. Here, we disrupted the P. berghei plasmoredoxin gene that encodes a parasite-specific 22 kDa member of the thioredoxin superfamily. The successful generation of plasmoredoxin knockout mutants in the rodent model malaria parasite and phenotypic analysis during life cycle progression revealed a non-vital role in vivo. Our findings suggest that plasmoredoxin fulfils a specialized and dispensable role for Plasmodium and highlights the need for target validation to inform drug development strategies.

The relationship between blood potassium, blood lactate, and electromyography signals related to fatigue in a progressive cycling exercise test.

Science.gov (United States)

Tenan, Matthew S; McMurray, Robert G; Blackburn, B Troy; McGrath, Melanie; Leppert, Kyle

2011-02-01

Local muscle fatigue may be related to potassium efflux from the muscle cell and/or lactate accumulation within the muscle. Local fatigue causes a decrease in median frequency (MPF) of the electromyogram's power spectrum during isometric contractions but its relationship to changes in potassium and lactate during dynamic exercise is equivocal. Thus, this investigation evaluated relationships between changes in the MPF from the vastus lateralis and blood levels of lactate and potassium during an incremental cycling test and recovery. Trained cyclists (n=8) completed a discontinuous, graded cycle test to exhaustion under normal and glycogen-reduced conditions. The glycogen reduced condition promoted an environment of lower lactate production while permitting a consistent potassium response. Blood samples and maximal isometric EMG data were collected at the end of each stage and during recovery. Maximal lactate levels were ∼ 60% lower in the glycogen reduced condition; potassium was similar between trials. MPF did not change significantly at volitional fatigue. Further, MPF was not significantly related to lactate (p>0.27) or potassium (p>0.16) in either condition. Though both lactate and potassium have been implicated as factors relating to local muscle fatigue, neither is significantly related to changes in MPF during or after progressive exercise on a cycle ergometer. Copyright © 2010 Elsevier Ltd. All rights reserved.

Indirect immobilized Jagged1 suppresses cell cycle progression and induces odonto/osteogenic differentiation in human dental pulp cells.

Science.gov (United States)

Manokawinchoke, Jeeranan; Nattasit, Praphawi; Thongngam, Tanutchaporn; Pavasant, Prasit; Tompkins, Kevin A; Egusa, Hiroshi; Osathanon, Thanaphum

2017-08-31

Notch signaling regulates diverse biological processes in dental pulp tissue. The present study investigated the response of human dental pulp cells (hDPs) to the indirect immobilized Notch ligand Jagged1 in vitro. The indirect immobilized Jagged1 effectively activated Notch signaling in hDPs as confirmed by the upregulation of HES1 and HEY1 expression. Differential gene expression profiling using an RNA sequencing technique revealed that the indirect immobilized Jagged1 upregulated genes were mainly involved in extracellular matrix organization, disease, and signal transduction. Downregulated genes predominantly participated in the cell cycle, DNA replication, and DNA repair. Indirect immobilized Jagged1 significantly reduced cell proliferation, colony forming unit ability, and the number of cells in S phase. Jagged1 treated hDPs exhibited significantly higher ALP enzymatic activity, osteogenic marker gene expression, and mineralization compared with control. Pretreatment with a γ-secretase inhibitor attenuated the Jagged1-induced ALP activity and mineral deposition. NOTCH2 shRNA reduced the Jagged1-induced osteogenic marker gene expression, ALP enzymatic activity, and mineral deposition. In conclusion, indirect immobilized Jagged1 suppresses cell cycle progression and induces the odonto/osteogenic differentiation of hDPs via the canonical Notch signaling pathway.

Fuel cycle studies for the Dragon HTR

Energy Technology Data Exchange (ETDEWEB)

Desoisa, J A; Nunn, R M; Twitchin, A E

1971-02-15

This note reports the progress made at B.N.L. in the study of the fuel cycle for the HTR design described by Daub (1970). The primary purpose of the study is to examine the special problems of the approach to equilibrium fuel cycle.

Effects of low dose radiation on tumor apoptosis, cell cycle progression and changes of apoptosis-related protein bcl-2 in tumor-bearing mice

International Nuclear Information System (INIS)

Yu Hongsheng; Fei Conghe; Shen Fangzhen; Liang Jun

2003-01-01

Objective: To study the effect of low dose radiation (LDR) on tumor apoptosis, cell cycle progression and changes of apoptosis-related protein bcl-2 in tumor-bearing mice. Methods: Kunming stain male mice were implanted with S180 sarcoma cells in the left inguen subcutaneously as an in situ experimental animal model. Seven days after implantation, the mice were given 75 mGy whole-body γ-irradiation. At 24 and 48 h after irradiation, all mice were sacrificed to measure the tumor volume, and tumor cell apoptosis, cell cycle progression were analyzed by flow cytometry. The expression of apoptosis-related protein bcl-2 and the apoptotic rate of tumor cells were observed by immunohistochemistry and electron microscopy. Results: Tumor growth was significantly slowed down after LDR (P 1 phase and the expression of bcl-2 protein decreased at 24 h. Apoptotic rate of tumor cells increased significantly at 48 h after LDR. Conclusion: LDR could cause a G 1 -phase arrest and increase the apoptosis of tumor cells through the low level of apoptosis-related protein bcl-2 in the tumor-bearing mice. The organized immune function and anti-tumor ability are markedly increased after LDR. The study provides practical evidence of clinical application to cancer treatment

Role of p53 status in radiation sensitivity and cell cycle progression

International Nuclear Information System (INIS)

Zellars, Richard C.; Loney, Tania; Schott, Ann F.; Davis, Mary A.; Maybaum, Jonathan; Clarke, Michael F.; Lawrence, Theodore S.

1995-01-01

Purpose: Although p53 function plays a major role in G1 arrest after radiation, the influence of p53 status on progress through other phases of the cell cycle and on radiation sensitivity of human tumors is less clear. We investigated these issues using cells with a conditional expression system for wild type p53. Methods: A temperature sensitive murine wild type p53 plasmid was used (Ginsberg D, et al: Mol. Cell.Biol . 11:582, 1991). At the permissive temperature (32 deg. C), this plasmid produces a protein which assumes a conformation that exhibits wild type p53 function. However, when cells are cultured at 38 deg. C, this protein assumes an inactive conformation. HT29 human colon cancer cells (which are p53 mutant) were transduced with this plasmid (designated PEP A and PEP G cells) or a control vector (designated CCH1 cells) using electroporation and Geneticin selection. The presence of murine p53 transcript in the PEP cells was confirmed by Northern analysis. Results: Cells were cultured under 3 conditions: 1) 38 deg. C at all times; 2) 32 deg. C for 24 hours prior to irradiation and 3) 32 deg. C for 24 hours after irradiation. We found that culturing under permissive temperatures produced a small decrease in surviving fraction in the PEP clones (0.61 ± 0.10 and 0.64 ± 0.07, for PEP A and G, respectively) but not the CCH1 controls (1.14 ± 0.15). PEP cells tended to be more radiosensitive than CCH1 cells (even under non-permissive conditions) and demonstrated a trend towards increased radiosensitivity under both Conditions 2 and 3. In addition, flow cytometry revealed that a 24 hour exposure to permissive conditions increased the fraction of cells in G1 slightly and in G2/M substantially. S phase was almost absent. Conclusion: Restoration of p53 function in HT29 human colon cancer cells using this temperature sensitive system produced increased cytotoxicity and radiation sensitivity as well as cell cycle redistribution. It will be important to assess the

Fuel cycles for the 80's

International Nuclear Information System (INIS)

1980-01-01

Papers presented at the American Nuclear Society's topical meeting on the fuel cycle are summarized. Present progress and goals in the areas of fuel fabrication, fuel reprocessing, spent fuel storage, accountability, and safeguards are reported. Present governmental policies which affect the fuel cycle are also discussed. Individual presentations are processed for inclusion in the Energy Data Base

Prospects and progress status of the Advanced Fuel Cycle System in Japan

International Nuclear Information System (INIS)

Namba, T.; Funasaka, H.; Nagaoki, Y.; Sagayama, Y.

2004-01-01

Feasibility study on commercialized FR cycle systems has been carried out by a joint team established within JNC with the participation of all parties concerned in Japan since July, 1999. This research program aims to clarify various perspectives for commercializing the FR cycle. This also will suggest development strategies that correspond flexibly to diverse future social needs in the 21. century. After the Phase I, Phase II stage started from April, 2001 for five years. In this stage the highly feasible candidate concepts for FR cycle systems screened in the previous step have been intensively studied by both design study and elemental process tests. In this paper, results of mid-term evaluation of these concepts for FR cycle systems will be summarized

Prospects and progress status of the Advanced Fuel Cycle System in Japan

Energy Technology Data Exchange (ETDEWEB)

Namba, T.; Funasaka, H.; Nagaoki, Y.; Sagayama, Y

2004-07-01

Feasibility study on commercialized FR cycle systems has been carried out by a joint team established within JNC with the participation of all parties concerned in Japan since July, 1999. This research program aims to clarify various perspectives for commercializing the FR cycle. This also will suggest development strategies that correspond flexibly to diverse future social needs in the 21. century. After the Phase I, Phase II stage started from April, 2001 for five years. In this stage the highly feasible candidate concepts for FR cycle systems screened in the previous step have been intensively studied by both design study and elemental process tests. In this paper, results of mid-term evaluation of these concepts for FR cycle systems will be summarized.

Transcriptional profiling of extracellular amino acid sensing in Saccharomyces cerevisiae and the role of Stp1p and Stp2p

DEFF Research Database (Denmark)

Eckert-Boulet, Nadine; Nielsen, P.S.; Friis, Carsten

2004-01-01

Tdh1p and glucokinase (Glk1p), shows increased transcription levels in either or both of the mutants. Also, most of the structural genes involved in trehalose and glycogen synthesis and a few genes in the glyoxylate cycle and the pentose phosphate pathway are derepressed in the ssy1 and stp1 stp2...

Endothelial nitric oxide synthase deficiency influences normal cell cycle progression and apoptosis in trabecular meshwork cells

Directory of Open Access Journals (Sweden)

Qiong Liao

2016-06-01

Full Text Available AIM: To clarify how the endothelial nitric oxide synthase (eNOS, NOS3 make effect on outflow facility through the trabecular meshwork (TM. METHODS: Inhibition of NOS3 gene expression in human TM cells were conducted by three siRNAs. Then the mRNA and protein levels of NOS3 in siRNA-treated and negative control (NC cells were determined, still were the collagen, type IV, alpha 1 (COL4A1 and fibronectin 1 by real-time PCR and Western blot analysis. In addition, NOS3 concentrations in culture supernatant fluids of TM cells were measured. Cell cycle and cell apoptosis analysis were performed using flow cytometry. RESULTS: The mRNA level of NOS3 was decreased by three different siRNA interference, similar results were obtained not only of the relative levels of NOS3 protein, but also the expression levels of COL4A1 and fibronectin 1. The number of cells in S phase was decreased, while contrary result was obtained in G2 phase. The number of apoptotic cells in siRNA-treated groups were significant increased compared to the NC samples. CONCLUSION: Abnormal NOS3 expression can make effects on the proteins levels of extracellular matrix component (e.g. fibronectin 1 and COL4A1. Reduced NOS3 restrains the TM cell cycle progression at the G2/M-phase transition and induced cell apoptosis.

Cloning and expression of isocitrate lyase from human round worm Strongyloides stercoralis

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Siddiqui A.A.

2000-09-01

Full Text Available A full length cDNA (1463 bp encoding isocitrate lyase (EC 4.1.3.1 of Strongyloides stercoralis is described. The nucleotide sequence of this insert identified a cDNA coding for the isocitrate lyase. The conceptually translated amino acid sequence of the open reading frame for S. stercoralis isocitrate lyase encodes a 450 amino acid residue protein with an apparent molecular weight of 50 kDa and a predicted pl of 6.39. The sequence is 69 % A/T, reflecting a characteristic A/T codon bias of S. stercoralis. The amino acid sequence of S. stercoralis isocitrate lyase is compared with bifunctional glyoxylate cycle protein of Caenorhabditis elegans and isocitrate lyases from Chlamydomonas reinhardtii and Myxococcus xanthus. The full length cDNA of S. stercoralis was expressed in pRSET vector and bacteriophage T7 promoter based expression system. S. stercoralis lyase recombinant protein, purified via immobilized metal affinity chromatography, showed a molecular mass of 50 kDa on polyacrylamide gels. The role of isocitrate lyase in the glyoxylate cycle and energy metabolism of S. stercoralis is also discussed.

AECL's progress in DUPIC fuel development

International Nuclear Information System (INIS)

Sullivan, J.D.; Ryz, M.A.; Lee, J.W.

1997-01-01

Previous papers described progress in choosing a fabrication route for the DUPIC (Direct Use of Spent PWR Fuel in CANDU) fuel cycle [1], details of the OREOX (Oxidation Reduction of Oxide fuel) process, and preliminary results of out-cell and small-scale in-cell experiments [2]. AECL's project to develop the DUPIC fuel cycle has now progressed to the stage of fabricating DUPIC fuel elements for irradiation testing in a research reactor. Because of the high radiation fields around the spent PWR fuel, all work is being done in hot cells. The equipment used for fabrication of the DUPIC fuel elements is described in this paper. The commissioning, in-cell installation and current status of the fabrication process are also described and plans for the completion of this phase of the DUPIC project are outlined. The goal of this phase of the project is demonstration of the technical feasibility of the DUPIC fuel cycle. (author)

Annual progress report 1981

International Nuclear Information System (INIS)

1982-01-01

This annual progress report of the CEA Protection and Nuclear Safety Institut outlines a brief description of the progress made in each section of the Institut. Research activities of the Protection department include, radiation effects on man, radioecology and environment radioprotection techniques. Research activities of the Nuclear Safety department include, reactor safety analysis, fuel cycle facilities safety analysis, safety research programs. The third section deals with nuclear material security including security of facilities, security of nuclear material transport and monitoring of nuclear material management [fr

BisGMA/TEGDMA dental nanocomposites containing glyoxylic acid-modified high-aspect ratio hydroxyapatite nanofibers with enhanced dispersion

International Nuclear Information System (INIS)

Chen Liang; Yu Qingsong; Li Hao; Xu Changqi; Wang Yong; Shi Jian

2012-01-01

The purpose of this research was to investigate the influence of the glyoxylic acid (GA) modification of hydroxyapatite (HAP) nanofibers on their dispersion in bisphenol A glycidyl methacrylate (BisGMA)/triethylene glycol dimethacrylate (TEGDMA) dental composites and also to investigate the mechanical properties, water absorption and water solubility of the resulting dental resins and composites. Scanning/transmission electron microscopy images showed that microsized HAP nanofiber bundles could be effectively broken down into individual HAP nanofibers with an average length of ∼15 µm after the surface modification process. Fourier transform infrared spectroscopy, x-ray photoelectron spectroscopy and thermal gravimetric analysis characterization confirmed that GA was chemically grafted on the HAP nanofiber surface, hypothetically by reacting with the amine group on the HAP nanofiber surface. The enhanced dispersion of HAP nanofibers in the dental matrix led to increased biaxial flexural strength (BFS) compared with the corresponding dental resins and composites filled with untreated HAP nanofibers. In addition, impregnation of small mass fractions of the GA-modified HAP nanofibers into the BisGMA/TEGDMA dental resins (5 wt%, 10 wt%) or composites (2 wt%, 3 wt%) could also substantially improve the BFS in comparison with the controls (pure resins or dental composites filled with silica particles alone). Larger mass fractions could not increase the mechanical property further or even degraded the BFS values. Water behavior testing results indicated that the addition of the GA-modified HAP nanofibers resulted in higher water absorption and water solubility values, which are not preferred for clinical application. In summary, well-dispersed HAP nanofibers and their dental composites with enhanced mechanical properties have been successfully fabricated, but the water absorption and water solubility of such dental composites need to be further improved. (paper)

Integrating Menstrual Cycle Data into The Smart Home

DEFF Research Database (Denmark)

Homewood, Sarah

2017-01-01

Menstrual cycle data gathered through self-tracking apps are increasingly used to understand, control and monitor bodies that menstruate. This work-in-progress explores the effects of representing menstrual cycle data within the smart home through critical design and planned fieldwork. Themes...... presented in this paper include the taboo of menstrual cycles, the question of what kinds of data do we represent in the smart home and menstrual cycle tracking technologies as examples of affective computing....

1985. Annual progress report

International Nuclear Information System (INIS)

1986-01-01

This annual progress report of the CEA Protection and Nuclear Safety Institut outlines a description of the progress made in each sections of the Institut Research activities of the different departments include: reactor safety analysis, fuel cycle facilities analysis; and associated safety research programs (criticality, sites, transport ...), radioecology and environmental radioprotection techniques; data acquisition on radioactive waste storage sites; radiation effects on man, studies on radioprotection techniques; nuclear material security including security of facilities, security of nuclear material transport, and monitoring of nuclear material management; nuclear facility decommissioning; and finally the public information [fr

A novel parameter, cell-cycle progression index, for radiation dose absorbed estimation in the premature chromosome condensation assay

International Nuclear Information System (INIS)

Miura, Tomisato; Kasai, Kosuke; Nakano, Manabu; Nakata, Akifumi; Yoshida, Mitsuaki A.; Abe, Yu; Tsushima, Eiki; Ossetrova, Natalia I.; Blakely, William F.

2014-01-01

The calyculin A-induced premature chromosome condensation (PCC) assay is a simple and useful method for assessing the cell-cycle distribution in cells, since calyculin A induces chromosome condensation in various phases of the cell cycle. In this study, a novel parameter, the cell-cycle progression index (CPI), in the PCC assay was validated as a novel bio-marker for bio-dosimetry. Peripheral blood was drawn from healthy donors after informed consent was obtained. CPI was investigated using a human peripheral blood lymphocyte (PBL) ex vivo irradiation ( 60 Co-gamma rays: ∼0.6 Gy min -1 , or X ray: 1.0 Gy min -1 ; 0-10 Gy) model. The calyculin A-induced PCC assay was performed for chromosome preparation. PCC cells were divided into the following five categories according to cell-cycle stage: non-PCC, G1-PCC, S-PCC, G2/M-PCC and M/A-PCC cells. CPI was calculated as the ratio of G2/M-PCC cells to G1-PCC cells. The PCC-stage distribution varied markedly with irradiation doses. The G1-PCC cell fraction was significantly reduced, and the G2/M-PCC cell fraction increased, in 10-Gy-irradiated PBL after 48 h of culture. CPI levels were fitted to an exponential dose-response curve with gamma-ray irradiation [y = 0.6729 + 0.3934 exp(0.5685D), r = 1.0000, p < 0.0001] and X-ray irradiation [y = -0.3743 + 0.9744 exp(0.3321D), r = 0.9999, p < 0.0001]. There were no significant individual (p = 0.853) or gender effects (p = 0.951) on the CPI in the human peripheral blood ex vivo irradiation model. Furthermore, CPI measurements are rapid (< 15 min per case). These results suggest that the CPI is a useful screening tool for the assessment of radiation doses received ranging from 0 to 10 Gy in radiation exposure early after a radiation event, especially after a mass-casualty radiological incident. (authors)

Activation of mammalian target of rapamycin signaling promotes cell cycle progression and protects cells from apoptosis in mantle cell lymphoma.

Science.gov (United States)

Peponi, Evangelia; Drakos, Elias; Reyes, Guadalupe; Leventaki, Vasiliki; Rassidakis, George Z; Medeiros, L Jeffrey

2006-12-01

Mantle cell lymphoma (MCL) is characterized by the t(11;14) and cyclin D1 overexpression. However, additional molecular events are most likely required for oncogenesis, possibly through cell cycle and apoptosis deregulation. We hypothesized that mammalian target of rapamycin (mTOR) is activated in MCL and contributes to tumor proliferation and survival. In MCL cell lines, pharmacological inhibition of the phosphoinositide 3-kinase/AKT pathway was associated with decreased phosphorylation (activation) of mTOR and its downstream targets phosphorylated (p)-4E-BP1, p-p70S6 kinase, and p-ribosomal protein S6, resulting in apoptosis and cell cycle arrest. These changes were associated with down-regulation of cyclin D1 and the anti-apoptotic proteins cFLIP, BCL-XL, and MCL-1. Furthermore, silencing of mTOR expression using mTOR-specific short interfering RNA decreased phosphorylation of mTOR signaling proteins and induced cell cycle arrest and apoptosis. Silencing of eukaryotic initiation factor (eIF4E), a downstream effector of mTOR, recapitulated these results. We also assessed mTOR signaling in MCL tumors using immunohistochemical methods and a tissue microarray: 10 of 30 (33%) expressed Ser473p-AKT, 13 of 21 (62%) Ser2448p-mTOR, 22 of 22 (100%) p-p70S6K, and 5 of 20 (25%) p-ribosomal protein S6. Total eIF4E binding protein 1 and eukaryotic initiation factor 4E were expressed in 13 of 14 (93%) and 16 of 29 (55%) MCL tumors, respectively. These findings suggest that the mTOR signaling pathway is activated and may contribute to cell cycle progression and tumor cell survival in MCL.

P27 in cell cycle control and cancer

DEFF Research Database (Denmark)

Møller, Michael Boe

2000-01-01

In order to survive, cells need tight control of cell cycle progression. The control mechanisms are often lost in human cancer cells. The cell cycle is driven forward by cyclin-dependent kinases (CDKs). The CDK inhibitors (CKIs) are important regulators of the CDKs. As the name implies, CKIs were...

Chemical Engineering Division fuel cycle programs. Quarterly progress report, July-September 1978

Energy Technology Data Exchange (ETDEWEB)

Steindler, M.J.; Ader, M.; Barletta, R.E.

1980-01-01

Fuel cycle work included hydraulic performance and extraction efficiency of eight-stage centrifugal contactors, flowsheet for the Aralex process, Ru and Zr extraction in a miniature centrifugal contactor, study of Zr aging in the organic phase and its effect on Zr extraction and hydraulic testing of the 9-cm-ID contactor. Work for predicting accident consequences in LWR fuel processing covered the relation between energy input (to subdivide a solid) and the modes of particle size frequency distribution. In the pyrochemical and dry processing program corrosion-testing materials for containment vessels and equipment for studying carbide reactions in bismuth is under way. Analytical studies have been made of salt-transport processes; efforts to spin tungsten crucibles 13 cm dia continue, and other information on tungsten fabrication is being assembled; the process steps of the chloride volatility process have been demonstrated and the thoria powder product used to produce oxide pellets; solubility of UO/sub 2/, PuO/sub 2/, and fission products in molten alkali nitrates is being investigated; work was continued on reprocessing actinide oxides by extracting the actinides into ammonium chloroaluminate from bismuth; the preparation of thorium-uranium carbide from the oxide is being studied as a means of improving the oxide reactivity; studies are in progress on producing uranium metal and decontaminated ThO/sub 2/ by the reaction of (Th,U)O/sub 2/ solid solution in molten salts containing ThCl/sub 4/ and thorium metal chips. In the molten tin process, no basic thermodynamic or kinetic factors have been found that may limit process development.

Phospho-Ser/Thr-binding domains: navigating the cell cycle and DNA damage response.

Science.gov (United States)

Reinhardt, H Christian; Yaffe, Michael B

2013-09-01

Coordinated progression through the cell cycle is a complex challenge for eukaryotic cells. Following genotoxic stress, diverse molecular signals must be integrated to establish checkpoints specific for each cell cycle stage, allowing time for various types of DNA repair. Phospho-Ser/Thr-binding domains have emerged as crucial regulators of cell cycle progression and DNA damage signalling. Such domains include 14-3-3 proteins, WW domains, Polo-box domains (in PLK1), WD40 repeats (including those in the E3 ligase SCF(βTrCP)), BRCT domains (including those in BRCA1) and FHA domains (such as in CHK2 and MDC1). Progress has been made in our understanding of the motif (or motifs) that these phospho-Ser/Thr-binding domains connect with on their targets and how these interactions influence the cell cycle and DNA damage response.

Effects of menstrual cycle phase on cocaine self-administration in rhesus macaques.

Science.gov (United States)

Cooper, Ziva D; Foltin, Richard W; Evans, Suzette M

2013-01-01

Epidemiological findings suggest that men and women vary in their pattern of cocaine use resulting in differences in cocaine dependence and relapse rates. Preclinical laboratory studies have demonstrated that female rodents are indeed more sensitive to cocaine's reinforcing effects than males, with estrous cycle stage as a key determinant of this effect. The current study sought to extend these findings to normally cycling female rhesus macaques, a species that shares a nearly identical menstrual cycle to humans. Dose-dependent intravenous cocaine self-administration (0.0125, 0.0250, and 0.0500 mg/kg/infusion) using a progressive-ratio schedule of reinforcement was determined across the menstrual cycle. The menstrual cycle was divided into 5 discrete phases - menses, follicular, periovulatory, luteal, and late luteal phases - verified by the onset of menses and plasma levels of estradiol and progesterone. Dependent variables including number of infusions self-administered per session, progressive ratio breakpoint, and cocaine intake were analyzed according to cocaine dose and menstrual cycle phase. Analysis of plasma hormone levels verified phase-dependent fluctuations of estradiol and progesterone, with estrogen levels peaking during the periovulatory phase, and progesterone peaking during the luteal phase. Progressive ratio breakpoint, infusions self-administered, and cocaine intake did not consistently vary based on menstrual cycle phase. These findings demonstrate that under the current experimental parameters, the reinforcing effects of cocaine did not vary across the menstrual cycle in a systematic fashion in normally cycling rhesus macaques. Copyright © 2012 Elsevier Inc. All rights reserved.

The Solar Cycle and, How Do We Know What We Know?

Science.gov (United States)

Adams, Mitzi

2013-01-01

Through the use of observations, mathematics, mathematical tools (such as graphs), inference, testing, and prediction we have gathered evidence that there are sunspots, a solar cycle, and have begun to understand more about our star, the Sun. We are making progress in understanding the cause of the solar cycle. We expect solar cycle 24 to peak soon. Cycle 24 will be the smallest cycle in 100 years.

Overexpression of high molecular weight FGF-2 forms inhibits glioma growth by acting on cell-cycle progression and protein translation

International Nuclear Information System (INIS)

Lemiere, Sylvie; Azar, Rania; Belloc, Francis; Guersel, Demir; Pyronnet, Stephane; Bikfalvi, Andreas; Auguste, Patrick

2008-01-01

In order to clarify the role of HMW FGF-2 in glioma development and angiogenesis, we over-expressed different human FGF-2 isoforms in C6 rat glioma cell line using a tetracycline-regulated expression system. Phenotypic modifications were analyzed in vitro and compared to untransfected cells or to cells over-expressing 18 kDa FGF-2 or all FGF-2 isoforms. In particular, we demonstrate that HMW FGF-2 has unique features in inhibiting glioma cell proliferation. HMW FGF-2 expressing cells showed a cell-cycle arrest at the G2M, demonstrating a role of HMW FGF-2 in controlling the entry in mitosis. Moreover, hydroxyurea was ineffective in blocking cells at the G1S boundary when HMW FGF-2 was expressed. We also show that the HMW FGF-2 isoforms inhibit 4E-BP1 phosphorylation at critical sites restoring the translation inhibitory activity of 4E-BP1. In vivo, inhibition of tumor growth was observed when cells expressed HMW FGF-2. This indicates that HMW FGF-2 inhibits tumor growth in glioma cells by acting on cell-cycle progression and protein translation

In silico design and biological evaluation of a dual specificity kinase inhibitor targeting cell cycle progression and angiogenesis.

Science.gov (United States)

Latham, Antony M; Kankanala, Jayakanth; Fearnley, Gareth W; Gage, Matthew C; Kearney, Mark T; Homer-Vanniasinkam, Shervanthi; Wheatcroft, Stephen B; Fishwick, Colin W G; Ponnambalam, Sreenivasan

2014-01-01

Protein kinases play a central role in tumor progression, regulating fundamental processes such as angiogenesis, proliferation and metastasis. Such enzymes are an increasingly important class of drug target with small molecule kinase inhibitors being a major focus in drug development. However, balancing drug specificity and efficacy is problematic with off-target effects and toxicity issues. We have utilized a rational in silico-based approach to demonstrate the design and study of a novel compound that acts as a dual inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2) and cyclin-dependent kinase 1 (CDK1). This compound acts by simultaneously inhibiting pro-angiogenic signal transduction and cell cycle progression in primary endothelial cells. JK-31 displays potent in vitro activity against recombinant VEGFR2 and CDK1/cyclin B proteins comparable to previously characterized inhibitors. Dual inhibition of the vascular endothelial growth factor A (VEGF-A)-mediated signaling response and CDK1-mediated mitotic entry elicits anti-angiogenic activity both in an endothelial-fibroblast co-culture model and a murine ex vivo model of angiogenesis. We deduce that JK-31 reduces the growth of both human endothelial cells and human breast cancer cells in vitro. This novel synthetic molecule has broad implications for development of similar multi-kinase inhibitors with anti-angiogenic and anti-cancer properties. In silico design is an attractive and innovative method to aid such drug discovery.

Preparations for the Integral Fast Reactor fuel cycle demonstration

International Nuclear Information System (INIS)

Lineberry, M.J.; Phipps, R.D.

1989-01-01

Modifications to the Hot Fuel Examination Facility-South (HFEF/S) have been in progress since mid-1988 to ready the facility for demonstration of the unique Integral Fast Reactor (IFR) pyroprocess fuel cycle. This paper updates the last report on this subject to the American Nuclear Society and describes the progress made in the modifications to the facility and in fabrication of the new process equipment. The IFR is a breeder reactor, which is central to the capability of any reactor concept to contribute to mitigation of environmental impacts of fossil fuel combustion. As a fast breeder, fuel of course must be recycled in order to have any chance of an economical fuel cycle. The pyroprocess fuel cycle, relying on a metal alloy reactor fuel rather than oxide, has the potential to be economical even at small-scale deployment. Establishing this quantitatively is one important goal of the IFR fuel cycle demonstration

Cell cycle related /sup 125/IUDR-induced-division delay

International Nuclear Information System (INIS)

Scheniderman, M.H.; Hofer, K.G.

1987-01-01

A series of experiments were run to determine if /sup 125/I-decays, in /sup 125/IUdR labeled DNA, specifically accumulated at 1, 3, 5, 7 and 9 hours after plating labeled mitotic cells caused a change in the rate or time of cell entry into mitosis. To accomplish this, a pool of labeled mitotic cells was selected in mitosis and plated in replicate flasks. /sup 125/I decays were accumulated in groups of cells by cooling (4 0 C) for 2 hours starting at the designated times. After rewarding, colcemid was added to arrest cells in mitosis. The rate of cell progression into mitosis for each cell cycle time of accumulation was determined by scoring the mitotic index of cells sampled as a function of time after addition of the colcemid. The results are summarized: (1) Decays from /sup 125/I in /sup 125/I(UdR) labeled DNA reduced the rate of cell progression into mitosis and delayed the time of initiation of mitosis. (2) The reduced rate of progression and the delayed time of initiation of mitosis were independent of the cell cycle time that /sup 125/I-decays were accumulated. (3) The reduced rate of progression after cell cycle accumulation of /sup 125/I decay was statistically indistinguishable from the corresponding controls. (4) The delayed initiation of mitosis after specific cell cycle accumulation of /sup 125/I- decays was greater than the corresponding control. The relationship of these data to DNA and non-DNA division delay target(s) is emphasized

Withaferin A and sulforaphane regulate breast cancer cell cycle progression through epigenetic mechanisms.

Science.gov (United States)

Royston, Kendra J; Paul, Bidisha; Nozell, Susan; Rajbhandari, Rajani; Tollefsbol, Trygve O

2018-07-01

Little is known about the effects of combinatorial dietary compounds on the regulation of epigenetic mechanisms involved in breast cancer prevention. The human diet consists of a multitude of components, and there is a need to elucidate how certain compounds interact in collaboration. Withaferin A (WA), found in the Indian winter cherry and documented as a DNA methyltransferase (DNMT) inhibitor, and sulforaphane (SFN), a well-known histone deacetylase (HDAC) inhibitor found in cruciferous vegetables, are two epigenetic modifying compounds that have only recently been studied in conjunction. The use of DNMT and HDAC inhibitors to reverse the malignant expression of certain genes in breast cancer has shown considerable promise. Previously, we found that SFN + WA synergistically promote breast cancer cell death. Herein, we determined that these compounds inhibit cell cycle progression from S to G2 phase in MDA-MB-231 and MCF-7 breast cancer. Furthermore, we demonstrate that this unique combination of epigenetic modifying compounds down-regulates the levels of Cyclin D1 and CDK4, and pRB; conversely, the levels of E2F mRNA and tumor suppressor p21 are increased independently of p53. We find these events coincide with an increase in unrestricted histone methylation. We propose SFN + WA-induced breast cancer cell death is attributed, in part, to epigenetic modifications that result in the modulated expression of key genes responsible for the regulation of cancer cell senescence. Copyright © 2018 Elsevier Inc. All rights reserved.

Cell cycle controls: potential targets for chemical carcinogens?

OpenAIRE

Afshari, C A; Barrett, J C

1993-01-01

The progression of the cell cycle is controlled by the action of both positive and negative growth regulators. The key players in this activity include a family of cyclins and cyclin-dependent kinases, which are themselves regulated by other kinases and phosphatases. Maintenance of balanced cell cycle controls may be directly linked to genomic stability. Loss of the check-points involved in cell cycle control may result in unrepaired DNA damage during DNA synthesis or mitosis leading to genet...

Global guidance on environmental life cycle impact assessment indicators: Progress and case study

DEFF Research Database (Denmark)

Frischknecht, Rolf; Fantke, Peter; Tschümperlin, Laura

2016-01-01

Purpose The life cycle impact assessment (LCIA) guidance flagship project of the United Nations Environment Programme (UNEP)/Society of Environmental Toxicology and Chemistry (SETAC) Life Cycle Initiative aims at providing global guidance and building scientific consensus on environmental LCIA in...

[Effects and mechanism of freeze-thawing cycles on key processes of nitrogen cycle in terrestrial ecosystem].

Science.gov (United States)

Wang, Li-qin; Qi, Yu-chun; Dong, Yun-she; Peng, Qin; Guo, Shu-fang; He, Yun-long; Yan, Zhong-qing

2015-11-01

As a widespread natural phenomenon in the soil of middle and high latitude as well as high altitude, freeze-thawing cycles have a great influence on the nitrogen cycle of terrestrial ecosystem in non-growing season. Freeze-thawing cycles can alter the physicochemical and biological properties of the soil, which thereby affect the migration and transformation of soil nitrogen. The impacts of freeze-thawing cycles on key processes of nitrogen cycle in terrestrial ecosystem found in available studies remain inconsistent, the mechanism is still not clear, and the research methods also need to be further explored and innovated. So it is necessary to sum up and analyze the existing achievements in order to better understand the processes of soil nitrogen cycle subjected to freeze-thawing cycles. This paper reviewed the research progress in China and abroad about the effects and mechanisms of freeze-thawing cycles on key processes of nitrogen cycle in terrestrial ecosystem, including mineralization, immobilization, nitrification and denitrification, N leakage and gaseous loss, and analyzed the deficiencies of extant research. The possible key research topics that should be urgently paid more attention to in the future were also discussed.

Reconstitution of TCA cycle with DAOCS to engineer Escherichia coli into an efficient whole cell catalyst of penicillin G.

Science.gov (United States)

Lin, Baixue; Fan, Keqiang; Zhao, Jian; Ji, Junjie; Wu, Linjun; Yang, Keqian; Tao, Yong

2015-08-11

Many medically useful semisynthetic cephalosporins are derived from 7-aminodeacetoxycephalosporanic acid (7-ADCA), which has been traditionally made by the polluting chemical method. Here, a whole-cell biocatalytic process based on an engineered Escherichia coli strain expressing 2-oxoglutarate-dependent deacetoxycephalosporin C synthase (DAOCS) for converting penicillin G to G-7-ADCA is developed. The major engineering strategy is to reconstitute the tricarboxylic acid (TCA) cycle of E. coli to force the metabolic flux to go through DAOCS catalyzed reaction for 2-oxoglutarate to succinate conversion. Then the glyoxylate bypass was disrupted to eliminate metabolic flux that may circumvent the reconstituted TCA cycle. Additional engineering steps were taken to reduce the degradation of penicillin G and G-7-ADCA in the bioconversion process. These steps include engineering strategies to reduce acetate accumulation in the biocatalytic process and to knock out a host β-lactamase involved in the degradation of penicillin G and G-7-ADCA. By combining these manipulations in an engineered strain, the yield of G-7-ADCA was increased from 2.50 ± 0.79 mM (0.89 ± 0.28 g/L, 0.07 ± 0.02 g/gDCW) to 29.01 ± 1.27 mM (10.31 ± 0.46 g/L, 0.77 ± 0.03 g/gDCW) with a conversion rate of 29.01 mol%, representing an 11-fold increase compared with the starting strain (2.50 mol%).

Genome-Wide Survey of Pseudomonas aeruginosa PA14 Reveals a Role for the Glyoxylate Pathway and Extracellular Proteases in the Utilization of Mucin

Science.gov (United States)

Flynn, Jeffrey M.; Phan, Chi

2017-01-01

ABSTRACT Chronic airway infections by the opportunistic pathogen Pseudomonas aeruginosa are a major cause of mortality in cystic fibrosis (CF) patients. Although this bacterium has been extensively studied for its virulence determinants, biofilm growth, and immune evasion mechanisms, comparatively little is known about the nutrient sources that sustain its growth in vivo. Respiratory mucins represent a potentially abundant bioavailable nutrient source, although we have recently shown that canonical pathogens inefficiently use these host glycoproteins as a growth substrate. However, given that P. aeruginosa, particularly in its biofilm mode of growth, is thought to grow slowly in vivo, the inefficient use of mucin glycoproteins may be relevant to its persistence within the CF airways. To this end, we used whole-genome fitness analysis, combining transposon mutagenesis with high-throughput sequencing, to identify genetic determinants required for P. aeruginosa growth using intact purified mucins as a sole carbon source. Our analysis reveals a biphasic growth phenotype, during which the glyoxylate pathway and amino acid biosynthetic machinery are required for mucin utilization. Secondary analyses confirmed the simultaneous liberation and consumption of acetate during mucin degradation and revealed a central role for the extracellular proteases LasB and AprA. Together, these studies describe a molecular basis for mucin-based nutrient acquisition by P. aeruginosa and reveal a host-pathogen dynamic that may contribute to its persistence within the CF airways. PMID:28507068

Segmentation and classification of cell cycle phases in fluorescence imaging.

Science.gov (United States)

Ersoy, Ilker; Bunyak, Filiz; Chagin, Vadim; Cardoso, M Christina; Palaniappan, Kannappan

2009-01-01

Current chemical biology methods for studying spatiotemporal correlation between biochemical networks and cell cycle phase progression in live-cells typically use fluorescence-based imaging of fusion proteins. Stable cell lines expressing fluorescently tagged protein GFP-PCNA produce rich, dynamically varying sub-cellular foci patterns characterizing the cell cycle phases, including the progress during the S-phase. Variable fluorescence patterns, drastic changes in SNR, shape and position changes and abundance of touching cells require sophisticated algorithms for reliable automatic segmentation and cell cycle classification. We extend the recently proposed graph partitioning active contours (GPAC) for fluorescence-based nucleus segmentation using regional density functions and dramatically improve its efficiency, making it scalable for high content microscopy imaging. We utilize surface shape properties of GFP-PCNA intensity field to obtain descriptors of foci patterns and perform automated cell cycle phase classification, and give quantitative performance by comparing our results to manually labeled data.

Opportunities for Collaborative Adaptive Management Progress: Integrating Stakeholder Assessments into Progress Measurement

Directory of Open Access Journals (Sweden)

Jim Berkley

2013-12-01

There are differences among stakeholders in the indicators they consider as relevant to the assessment of progress. Elucidating these differences can provide useful information about system components and relationships that are important to public support of a CAM program and progress. One of the sources of differences in progress assessments among stakeholders comes from their diverse perceptions about the desired and current states of the social-ecological systems. Stakeholder behavior can be inconsistent between group and individual settings. Individually they may make plans, based on their assessments, that do not conform to the group plan because of their unique interests and preferences. The results of this study need to be further tested. The framework should be used through multiple cycles to determine whether the information gathered with this approach results in additional progress as compared with past approaches. In particular, it would be helpful to test whether gathering such information resulted in a decrease in stakeholders electing to go outside of the CAM process to get their needs met.

Effects of light on respiration and development of photosynthetic cells. Renewal application and progress report, March 1-November 1, 1980

Energy Technology Data Exchange (ETDEWEB)

Gibbs, M.

1980-11-20

The oxyhydrogen reaction in the presence and absence of CO/sub 2/ was studied in H/sub 2/- adapted Scenedesmus obliquus by monitoring the initial rates of H/sub 2/, O/sub 2/, and /sup 14/CO/sub 2/ uptake and the effect of inhibitors on these rates. Glucose and acetate respiration was competitive with H/sub 2/ uptake. KCN inhibited equally respiration and the oxyhydrogen reaction in the presence and absence of CO/sub 2/. It was concluded that the oxyhydrogen reaction both in the absence and presence of CO/sub 2/ has properties in common with components of respiration and photosynthesis. Participation of these two processes in the oxyhydrogen reaction would require a closely linked shuttle between mitochondrion and chloroplast. Protoplasts and chloroplasts will be isolated from a H/sub 2/-adapted alga in order to elucidate the cooperation between the two organelles. Acetate was shown to stimulate H/sub 2/ photoproduction in H/sub 2/-adapted algae even more so than an uncoupler of electron transport. The role of these compounds will be evaluated either in terms of the glyoxylate cycle or electron acceptors resulting in formation of alcohols. The term chloroplast respiration was proposed to account for the breakdown of polyglucan within the chloroplast. A means of reoxidizing reduced pyridine nucleotide was required to complete the cycle. A new enzyme ascorbic acid reduced pyridine nucleotide peroxidase was isolated from the chloroplast. The characterization of this enzyme will continue.

The Brain-Computer Interface Cycle

NARCIS (Netherlands)

Gerven, Marcel; Farquhar, Jason; Schaefer, Rebecca; Vlek, Rutger; Geuze, Jeroen; Nijholt, Antinus; Ramsay, Nick; Haselager, Pim; Vuurpijl, Louis; Gielen, Stan; Desain, Peter

2009-01-01

Brain–computer interfaces (BCIs) have attracted much attention recently, triggered by new scientific progress in understanding brain function and by impressive applications. The aim of this review is to give an overview of the various steps in the BCI cycle, i.e., the loop from the measurement of

Theory of limit cycles

CERN Document Server

Ye, Yan-Qian; Lo, Chi Y

1986-01-01

Over the past two decades the theory of limit cycles, especially for quadratic differential systems, has progressed dramatically in China as well as in other countries. This monograph, updating the 1964 first edition, includes these recent developments, as revised by eight of the author's colleagues in their own areas of expertise. The first part of the book deals with limit cycles of general plane stationary systems, including their existence, nonexistence, stability, and uniqueness. The second section discusses the global topological structure of limit cycles and phase-portraits of quadratic systems. Finally, the last section collects important results that could not be included under the subject matter of the previous two sections or that have appeared in the literature very recently. The book as a whole serves as a reference for college seniors, graduate students, and researchers in mathematics and physics.

Outside-in control -Does plant cell wall integrity regulate cell cycle progression?

Science.gov (United States)

Gigli-Bisceglia, Nora; Hamann, Thorsten

2018-04-13

During recent years it has become accepted that plant cell walls are not inert objects surrounding all plant cells but are instead highly dynamic, plastic structures. They are involved in a large number of cell biological processes and contribute actively to plant growth, development and interaction with environment. Therefore, it is not surprising that cellular processes can control plant cell wall integrity while, simultaneously, cell wall integrity can influence cellular processes. In yeast and animal cells such a bi-directional relationship also exists between the yeast/animal extra-cellular matrices and the cell cycle. In yeast, the cell wall integrity maintenance mechanism and a dedicated plasmamembrane integrity checkpoint are mediating this relationship. Recent research has yielded insights into the mechanism controlling plant cell wall metabolism during cytokinesis. However, knowledge regarding putative regulatory pathways controlling adaptive modifications in plant cell cycle activity in response to changes in the state of the plant cell wall are not yet identified. In this review, we summarize similarities and differences in regulatory mechanisms coordinating extra cellular matrices and cell cycle activity in animal and yeast cells, discuss the available evidence supporting the existence of such a mechanism in plants and suggest that the plant cell wall integrity maintenance mechanism might also control cell cycle activity in plant cells. This article is protected by copyright. All rights reserved.

Morphology study on the depleted uranium as hydriding/dehydriding cycles

Energy Technology Data Exchange (ETDEWEB)

Chung, Dong-you, E-mail: dongyou@nfri.re.kr [National Fusion Research Institute, Daejeon (Korea, Republic of); Yun, Sei-Hun; Kang, Hyun-Goo; Chang, Min Ho; Oh, Yun Hee [National Fusion Research Institute, Daejeon (Korea, Republic of); Kang, Kweon Ho; Woo, Yoon Myung [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2016-11-01

Depleted Uranium (DU) is one of the strongest candidates as a getter material of hydrogen isotopes in the nuclear fusion reactor. In this work, small DU lump specimen with 99.8% purity was prepared for observation of morphology variation as hydriding/dehydriding cycles. Hydriding/dehydriding of DU was carried out more than 10 cycles for powder preparation. The pulverized DU specimen was safely handled in the glove box under Argon gas condition to minimize contact with oxygen and humidity. The morphology change according to hydriding/dehydriding cycles was observed by visual cell reactor, optical microscope and scanning electron microscope. The first hydriding of the small DU sample has progressed slowly with surface enlargement and volume expansion as time passes. After third hydriding/dehydriding cycles, most of DU was pulverized. The powder fineness of DU developed as hydriding/dehydriding cycle progresses. But the agglomerates of fine DU particles were observed. It was confirmed that the DU particles exist as porous agglomerates. And the particle agglomerate shows poor fluidity and even has the cohesive force.

In silico design and biological evaluation of a dual specificity kinase inhibitor targeting cell cycle progression and angiogenesis.

Directory of Open Access Journals (Sweden)

Antony M Latham

Full Text Available Protein kinases play a central role in tumor progression, regulating fundamental processes such as angiogenesis, proliferation and metastasis. Such enzymes are an increasingly important class of drug target with small molecule kinase inhibitors being a major focus in drug development. However, balancing drug specificity and efficacy is problematic with off-target effects and toxicity issues.We have utilized a rational in silico-based approach to demonstrate the design and study of a novel compound that acts as a dual inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2 and cyclin-dependent kinase 1 (CDK1. This compound acts by simultaneously inhibiting pro-angiogenic signal transduction and cell cycle progression in primary endothelial cells. JK-31 displays potent in vitro activity against recombinant VEGFR2 and CDK1/cyclin B proteins comparable to previously characterized inhibitors. Dual inhibition of the vascular endothelial growth factor A (VEGF-A-mediated signaling response and CDK1-mediated mitotic entry elicits anti-angiogenic activity both in an endothelial-fibroblast co-culture model and a murine ex vivo model of angiogenesis.We deduce that JK-31 reduces the growth of both human endothelial cells and human breast cancer cells in vitro. This novel synthetic molecule has broad implications for development of similar multi-kinase inhibitors with anti-angiogenic and anti-cancer properties. In silico design is an attractive and innovative method to aid such drug discovery.

Synchronization of construction, replenishment and leasing cycles with account of wave dynamics of innovation cycles in the construction and transport field

Science.gov (United States)

Alekseeva, Tatyana

2017-10-01

The article considers the contradictive nature of the basic cycles of the growth in construction, the core of which are construction cycles, replenishment cycles of the active part of fixed assets, innovation and investment cycles. All of the listed cycles objectively thwart the science and technology progress in construction. There are presented results of the study of finance leasing as an effective tool, that provides time reduction of the innovation replenishment cycle of the active part of fixed assets in construction. It takes into account the development and implementation terms of construction investment projects in order to timely support the innovation wave and enhance its efficiency in construction for a rapid transition of the construction investment complex and national economy to a new vector of growth.

Ablation of an Ovarian Tumor Family Deubiquitinase Exposes the Underlying Regulation Governing the Plasticity of Cell Cycle Progression in Toxoplasma gondii.

Science.gov (United States)

Dhara, Animesh; de Paula Baptista, Rodrigo; Kissinger, Jessica C; Snow, E Charles; Sinai, Anthony P

2017-11-21

The Toxoplasma genome encodes the capacity for distinct architectures underlying cell cycle progression in a life cycle stage-dependent manner. Replication in intermediate hosts occurs by endodyogeny, whereas a hybrid of schizogony and endopolygeny occurs in the gut of the definitive feline host. Here, we characterize the consequence of the loss of a cell cycle-regulated o varian tu mor (OTU family) deubiquitinase, OTUD3A of Toxoplasma gondii (TgOTUD3A; TGGT1_258780), in T. gondii tachyzoites. Rather than the mutation being detrimental, mutant parasites exhibited a fitness advantage, outcompeting the wild type. This phenotype was due to roughly one-third of TgOTUD3A-knockout (TgOTUD3A-KO) tachyzoites exhibiting deviations from endodyogeny by employing replication strategies that produced 3, 4, or 5 viable progeny within a gravid mother instead of the usual 2. We established the mechanistic basis underlying these altered replication strategies to be a dysregulation of centrosome duplication, causing a transient loss of stoichiometry between the inner and outer cores that resulted in a failure to terminate S phase at the attainment of 2N ploidy and/or the decoupling of mitosis and cytokinesis. The resulting dysregulation manifested as deviations in the normal transitions from S phase to mitosis (S/M) (endopolygeny-like) or M phase to cytokinesis (M/C) (schizogony-like). Notably, these imbalances are corrected prior to cytokinesis, resulting in the generation of normal progeny. Our findings suggest that decisions regarding the utilization of specific cell cycle architectures are controlled by a ubiquitin-mediated mechanism that is dependent on the absolute threshold levels of an as-yet-unknown target(s). Analysis of the TgOTUD3A-KO mutant provides new insights into mechanisms underlying the plasticity of apicomplexan cell cycle architecture. IMPORTANCE Replication by Toxoplasma gondii can occur by 3 distinct cell cycle architectures. Endodyogeny is used by asexual

Technical support for open-cycle MHD program. Progress report, July--December 1978

Energy Technology Data Exchange (ETDEWEB)

Doss, E D [ed.

1979-06-01

The support program for open-cycle MHD at Argonne National Laboratory is developing the analytical tools needed to investigate the performance of the major components in the combined cycle MHD/steam power system. The analytical effort is centered on the primary components of the system that are unique to MHD and also on the integration of these analytical representations into a model of the entire power producing system. The present project activities include modeling of the combustor, MHD channel, slag separator, and high-temperature air heater. In addition, these models are combined into a complete system model, which is at present capable of carrying out optimizations of the entire system relative to either thermodynamic efficiency or cost of electrical power. Also, in support of other aspects of the open-cycle program, test plans are developed and facility and program reviews are provided upon request in support of the needs and requirements of the DOE/MHD Division.

RPS27a promotes proliferation, regulates cell cycle progression and inhibits apoptosis of leukemia cells

Energy Technology Data Exchange (ETDEWEB)

Wang, Houcai; Yu, Jing; Zhang, Lixia; Xiong, Yuanyuan; Chen, Shuying; Xing, Haiyan; Tian, Zheng; Tang, Kejing; Wei, Hui; Rao, Qing; Wang, Min; Wang, Jianxiang, E-mail: wangjx@ihcams.ac.cn

2014-04-18

Highlights: • RPS27a expression was up-regulated in advanced-phase CML and AL patients. • RPS27a knockdown changed biological property of K562 and K562/G01 cells. • RPS27a knockdown affected Raf/MEK/ERK, P21 and BCL-2 signaling pathways. • RPS27a knockdown may be applicable for new combination therapy in CML patients. - Abstract: Ribosomal protein S27a (RPS27a) could perform extra-ribosomal functions besides imparting a role in ribosome biogenesis and post-translational modifications of proteins. The high expression level of RPS27a was reported in solid tumors, and we found that the expression level of RPS27a was up-regulated in advanced-phase chronic myeloid leukemia (CML) and acute leukemia (AL) patients. In this study, we explored the function of RPS27a in leukemia cells by using CML cell line K562 cells and its imatinib resistant cell line K562/G01 cells. It was observed that the expression level of RPS27a was high in K562 cells and even higher in K562/G01 cells. Further analysis revealed that RPS27a knockdown by shRNA in both K562 and K562G01 cells inhibited the cell viability, induced cell cycle arrest at S and G2/M phases and increased cell apoptosis induced by imatinib. Combination of shRNA with imatinib treatment could lead to more cleaved PARP and cleaved caspase-3 expression in RPS27a knockdown cells. Further, it was found that phospho-ERK(p-ERK) and BCL-2 were down-regulated and P21 up-regulated in RPS27a knockdown cells. In conclusion, RPS27a promotes proliferation, regulates cell cycle progression and inhibits apoptosis of leukemia cells. It appears that drugs targeting RPS27a combining with tyrosine kinase inhibitor (TKI) might represent a novel therapy strategy in TKI resistant CML patients.

Variable-cycle engines for supersonic cruise aircraft

Science.gov (United States)

Willis, E.

1976-01-01

Progress and the current status of the Variable Cycle Engine (VCE) study are reviewed with emphasis placed on the impact of technology advancements and design specifications. A large variety of VCE concepts are also examined.

Extracellular matrix collagen alters cell proliferation and cell cycle progression of human uterine leiomyoma smooth muscle cells.

Science.gov (United States)

Koohestani, Faezeh; Braundmeier, Andrea G; Mahdian, Arash; Seo, Jane; Bi, JiaJia; Nowak, Romana A

2013-01-01

Uterine leiomyomas (ULs) are benign tumors occurring in the majority of reproductive aged women. Despite the high prevalence of these tumors, little is known about their etiology. A hallmark of ULs is the excessive deposition of extracellular matrix (ECM), primarily collagens. Collagens are known to modulate cell behavior and function singularly or through interactions with integrins and growth factor-mediated mitogenic pathways. To better understand the pathogenesis of ULs and the role of ECM collagens in their growth, we investigated the interaction of leiomyoma smooth muscle cells (LSMCs) with two different forms of collagen, non-polymerized collagen (monomeric) and polymerized collagen (fibrillar), in the absence or presence of platelet-derived growth factor (PDGF), an abundant growth factor in ULs. Primary cultures of human LSMCS from symptomatic patients were grown on these two different collagen matrices and their morphology, cytoskeletal organization, cellular proliferation, and signaling pathways were evaluated. Our results showed that LSMCs had distinct morphologies on the different collagen matrices and their basal as well as PDGF-stimulated proliferation varied on these matrices. These differences in proliferation were accompanied by changes in cell cycle progression and p21, an inhibitory cell cycle protein. In addition we found alterations in the phosphorylation of focal adhesion kinase, cytoskeletal reorganization, and activation of the mitogen activated protein kinase (MAPK) signaling pathway. In conclusion, our results demonstrate a direct effect of ECM on the proliferation of LSMCs through interplay between the collagen matrix and the PDGF-stimulated MAPK pathway. In addition, these findings will pave the way for identifying novel therapeutic approaches for ULs that target ECM proteins and their signaling pathways in ULs.

Cycle-by-cycle exhaust temperature monitoring for detection of misfiring and combustion instability in reciprocating natural gas engines

Energy Technology Data Exchange (ETDEWEB)

Gardiner, D.P. [Nexum Research Corp., Kingston, ON (Canada); Bardon, M.F. [Royal Military Coll. of Canada, Kingston, ON (Canada). Dept. of Mechanical Engineering

2007-07-01

The effectiveness of a cycle-by-cycle exhaust temperature monitoring system on engines operating at or near their fully rate load capacity was examined. Tests were conducted on stationary industrial natural gas engines. The study evaluated the monitoring system's ability to detect isolated single misfires, as well as combustion instability during misfire-free operations when the air/fuel ratio of the engine was adjusted to progressively lower settings. The combustion instability level of the engines was quantified by determining the relative variability of the groups of consecutive cycles. The coefficient of variation of indicated mean effective pressure (COV of IMEP) was used to examine cyclic variability. A combustion instability index was used to quantify cyclic variability with cycle-by-cycle exhaust temperature monitoring. Two engines were tested, notably a Cummins QSK 19G turbocharged natural gas engine; and a Waukesha VHP L5790G industrial natural gas engine. The tests demonstrated that cycle-by-cycle exhaust temperature monitoring system was capable of detecting misfiring and combustion instabilities in natural gas engines. 6 refs., 9 figs.

Three Cycles of Radiofrequency Ablation Are More Efficacious Than Two in the Management of Morton's Neuroma.

Science.gov (United States)

Brooks, David; Parr, Adam; Bryceson, William

2018-04-01

Morton's neuroma is a common cause of forefoot pain. Outcomes of conservative therapy are mixed and many patients undergo operative intervention. Radiofrequency ablation has recently gained favor as a treatment option, although the optimal regime is unknown. This study investigates the effectiveness of 2 versus 3 cycles of radiofrequency ablation for the treatment of Morton's neuroma. We surveyed a cohort of patients with Morton's neuroma who had progressed to radiofrequency ablation after failed conservative treatment. Patients received either 2 or 3 cycles of radiofrequency ablation by a single surgeon. We assessed patients based on their change in numerical pain rating scale, symptom improvement, complications, and progression to surgical excision through a series of telephone interviews. Outcomes between the 2 treatment arms were compared by parametric tests. Twenty-eight patients were included in the study. Eighteen patients with 21 neuromas received 2 cycles and 10 patients with 11 neuromas received 3 cycles. Mean time of follow-up was 12.9 months. Overall, 88% of patients were either very or moderately satisfied with their outcome. In patients who received 2 cycles mean numerical pain scores decreased from 7.9 ± 1.1 to 3.4 ± 2.4 postprocedure. Three patients progressed to operative excision. In patients who received 3 cycles, numerical pain scores decreased from 8.0 ± 1.0 to 1.5 ± 2.0 postprocedure. One patient progressed to operative excision. Patients who received 3 cycles had reduced medium-term pain postoperatively compared with 2 cycles (3.4 ± 2.4 vs 1.5 ± 2.0, P = .011). Radiofrequency ablation provides a high rate of patient satisfaction in the treatment of Morton's neuroma with few side effects. It appears that 3 cycles may be superior to 2 cycles but a randomized controlled trial will be required to confirm these results. Intervention, Level III: Comparative study without concurrent controls.

Leverage and Deepening Business Cycle Skewness

DEFF Research Database (Denmark)

Jensen, Henrik; Petrella, Ivan; Ravn, Søren Hove

2017-01-01

We document that the U.S. economy has been characterized by an increasingly negative business cycle asymmetry over the last three decades. This finding can be explained by the concurrent increase in the financial leverage of households and firms. To support this view, we devise and estimate......, booms become progressively smoother and more prolonged than busts. We are therefore able to reconcile a more negatively skewed business cycle with the Great Moderation in cyclical volatility. Finally, in line with recent empirical evidence, financially-driven expansions lead to deeper contractions...

The nuclear fuel cycle

International Nuclear Information System (INIS)

Patarin, L.

2002-01-01

This book treats of the different aspects of the industrial operations linked with the nuclear fuel, before and after its use in nuclear reactors. The basis science of this nuclear fuel cycle is chemistry. Thus a recall of the elementary notions of chemistry is given in order to understand the phenomena involved in the ore processing, in the isotope enrichment, in the fabrication of fuel pellets and rods (front-end of the cycle), in the extraction of recyclable materials (residual uranium and plutonium), and in the processing and conditioning of wastes (back-end of the fuel cycle). Nuclear reactors produce about 80% of the French electric power and the Cogema group makes 40% of its turnover at the export. Thus this book contains also some economic and geopolitical data in order to clearly position the stakes. The last part, devoted to the management of wastes, presents the solutions already operational and also the research studies in progress. (J.S.)

Avian leukosis virus subgroup J promotes cell proliferation and cell cycle progression through miR-221 by targeting CDKN1B.

Science.gov (United States)

Ren, Chaoqi; Yu, Mengmeng; Zhang, Yao; Fan, Minghui; Chang, Fangfang; Xing, Lixiao; Liu, Yongzhen; Wang, Yongqiang; Qi, Xiaole; Liu, Changjun; Zhang, Yanping; Cui, Hongyu; Li, Kai; Gao, Li; Pan, Qing; Wang, Xiaomei; Gao, Yulong

2018-04-23

Avian leukosis virus subgroup J (ALV-J), a highly oncogenic retrovirus, causes leukemia-like proliferative diseases in chickens. microRNAs post-transcriptionally suppress targets and are involved in the development of various tumors. We previously showed that miR-221 is upregulated in ALV-J-induced tumors. In this study, we analyzed the possible function of miR-221 in ALV-J tumorigenesis. The target validation system showed that CDKN1B is a target of miR-221 and is downregulated in ALV-J infection. As CDKN1B arrests the cell cycle and regulates its progression, we analyzed the proliferation of ALV-J-infected DF-1 cells. ALV-J-infection-induced DF1 cell derepression of G1/S transition and overproliferation required high miR-221 expression followed by CDKN1B downregulation. Cell cycle pathway analysis showed that ALV-J infection induced DF-1 cell overproliferation via the CDKN1B-CDK2/CDK6 pathway. Thus, miR-221 may play an important role in ALV-J-induced aggressive growth of DF-1 cells; these findings have expanded our insights into the mechanism underlying ALV-J infection and tumorigenesis. Copyright © 2018 Elsevier Inc. All rights reserved.

Organic Acids: The Pools of Fixed Carbon Involved in Redox Regulation and Energy Balance in Higher Plants

Directory of Open Access Journals (Sweden)

Abir U Igamberdiev

2016-07-01

Full Text Available Organic acids are synthesized in plants as a result of the incomplete oxidation of photosynthetic products and represent the stored pools of fixed carbon accumulated due to different transient times of conversion of carbon compounds in metabolic pathways. When redox level in the cell increases, e.g., in conditions of active photosynthesis, the tricarboxylic acid (TCA cycle in mitochondria is transformed to a partial cycle supplying citrate for the synthesis of 2-oxoglutarate and glutamate (citrate valve, while malate is accumulated and participates in the redox balance in different cell compartments (via malate valve. This results in malate and citrate frequently being the most accumulated acids in plants. However, the intensity of reactions linked to the conversion of these compounds can cause preferential accumulation of other organic acids, e.g., fumarate or isocitrate, in higher concentrations than malate and citrate. The secondary reactions, associated with the central metabolic pathways, in particularly with the TCA cycle, result in accumulation of other organic acids that are derived from the intermediates of the cycle. They form the additional pools of fixed carbon and stabilize the TCA cycle. Trans-aconitate is formed from citrate or cis-aconitate, accumulation of hydroxycitrate can be linked to metabolism of 2-oxoglutarate, while 4-hydroxy-2-oxoglutarate can be formed from pyruvate and glyoxylate. Glyoxylate, a product of either glycolate oxidase or isocitrate lyase, can be converted to oxalate. Malonate is accumulated at high concentrations in legume plants. Organic acids play a role in plants in providing redox equilibrium, supporting ionic gradients on membranes, and acidification of the extracellular medium.

S-phase-dependent cell cycle disturbances caused by Aleutian mink disease parvovirus

DEFF Research Database (Denmark)

Oleksiewicz, M.B.; Alexandersen, Søren

1997-01-01

We examined replication of the autonomous parovirus Aleutian mink disease parovirus (ADV) in relation to cell cycle progression of permissive Crandell feline kidney (CRFK) cells. Flow cytometric analysis showed that ADV caused a composite, binary pattern of cell cycle arrest. ADV-induced cell cyc...

Improving the Thermostability and Optimal Temperature of a Lipase from the Hyperthermophilic Archaeon Pyrococcus furiosus by Covalent Immobilization

Directory of Open Access Journals (Sweden)

Roberta V. Branco

2015-01-01

Full Text Available A recombinant thermostable lipase (Pf2001Δ60 from the hyperthermophilic Archaeon Pyrococcus furiosus (PFUL was immobilized by hydrophobic interaction on octyl-agarose (octyl PFUL and by covalent bond on aldehyde activated-agarose in the presence of DTT at pH = 7.0 (one-point covalent attachment (glyoxyl-DTT PFUL and on glyoxyl-agarose at pH 10.2 (multipoint covalent attachment (glyoxyl PFUL. The enzyme’s properties, such as optimal temperature and pH, thermostability, and selectivity, were improved by covalent immobilization. The highest enzyme stability at 70°C for 48 h incubation was achieved for glyoxyl PFUL (around 82% of residual activity, whereas glyoxyl-DTT PFUL maintained around 69% activity, followed by octyl PFUL (27% remaining activity. Immobilization on glyoxyl-agarose improved the optimal temperature to 90°C, while the optimal temperature of octyl PFUL was 70°C. Also, very significant changes in activity with different substrates were found. In general, the covalent bond derivatives were more active than octyl PFUL. The E value also depended substantially on the derivative and the conditions used. It was observed that the reaction of glyoxyl-DTT PFUL using methyl mandelate as a substrate at pH 7 presented the best results for enantioselectivity E=22 and enantiomeric excess (ee (% = 91.

UV-induced changes in cell cycle and gene expression within rabbit lens epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Sidjanin, D. [Northern Illinois Univ., De Kalb, IL (United States). Dept. of Biological Sciences; Grdina, D. [Argonne National Lab., IL (United States); Woloschak, G.E. [Northern Illinois Univ., De Kalb, IL (United States). Dept. of Biological Sciences

1994-11-01

Damage to lens epithelial cells is a probable initiation process in cataract formation induced by ultraviolet radiation. These experiments investigated the ability of 254 nm radiation on cell cycle progression and gene expression in rabbit lens epithelial cell line N/N1003A. No changes in expression of c-fos, c-jun, alpha- tubulin, or vimentin was observed following UV exposure. Using flow cytometry, an accumulation of cells in G1/S phase of the cell cycle 1 hr following exposure. The observed changes in gene expression, especially the decreased histone transcripts reported here may play a role in UV induced inhibition of cell cycle progression.

Present status of technology development on decommissioning and waste management in Nuclear Cycle Backend Directorate. Progress in 2009

International Nuclear Information System (INIS)

Takahashi, Kuniaki; Ishigami, Tsutomu; Funabashi, Hideyuki; Meguro, Yoshihiro; Tachibana, Mitsuo

2010-11-01

It is an important issue to take measures against the matters on decommissioning of retired nuclear facilities and management of low-level radioactive waste arising from research activities and operation of nuclear facilities, and the measures must be taken with rational way by ensuring the safety. As the development, improvement, and proper deployment of technologies will be key factors, a technology development program is under way in Nuclear Cycle Backend Directorate taking account of these matters in cooperation with research and development institutes/centers in Japan Atomic Energy Agency. The technology development items are selected from the viewpoints of systematic implementation of measures and cost reduction; these include the development of computer systems for planning and evaluation of decommissioning programs, supercritical CO 2 fluid leaching method for decontamination, nitrate-ion degradation method, simple and rapid determination method for radioactivity of radioactive waste, safety assessment for waste disposal and so on. This report describes outline and progress of the technology development program conducted in FY2009 by the research and development unit. (author)

The homeoprotein DLX3 and tumor suppressor p53 co-regulate cell cycle progression and squamous tumor growth.

Science.gov (United States)

Palazzo, E; Kellett, M; Cataisson, C; Gormley, A; Bible, P W; Pietroni, V; Radoja, N; Hwang, J; Blumenberg, M; Yuspa, S H; Morasso, M I

2016-06-16

Epidermal homeostasis depends on the coordinated control of keratinocyte cell cycle. Differentiation and the alteration of this balance can result in neoplastic development. Here we report on a novel DLX3-dependent network that constrains epidermal hyperplasia and squamous tumorigenesis. By integrating genetic and transcriptomic approaches, we demonstrate that DLX3 operates through a p53-regulated network. DLX3 and p53 physically interact on the p21 promoter to enhance p21 expression. Elevating DLX3 in keratinocytes produces a G1-S blockade associated with p53 signature transcriptional profiles. In contrast, DLX3 loss promotes a mitogenic phenotype associated with constitutive activation of ERK. DLX3 expression is lost in human skin cancers and is extinguished during progression of experimentally induced mouse squamous cell carcinoma (SCC). Reinstatement of DLX3 function is sufficient to attenuate the migration of SCC cells, leading to decreased wound closure. Our data establish the DLX3-p53 interplay as a major regulatory axis in epidermal differentiation and suggest that DLX3 is a modulator of skin carcinogenesis.

Status of the breeder fuel cycle in the United States

International Nuclear Information System (INIS)

Burch, W.D.

1985-01-01

This paper reviews the status and plans for the fast reactor fuel cycle in the United States. The United States is undertaking a complete reexamination of its entire breeder program strategy, and the direction of the new program is not yet clear. Studies in progress to examine the associated fuel cycle strategies as they relate to the overall emerging breeder strategy are described. The present status of and recent developments in the fuel cycle R and D programs are summarized

Molecular machinery of signal transduction and cell cycle regulation in Plasmodium

OpenAIRE

Koyama, Fernanda C.; Chakrabarti, Debopam; Garcia, Célia R.S.

2009-01-01

The regulation of the Plasmodium cell cycle is not understood. Although the Plasmodium falciparum genome is completely sequenced, about 60% of the predicted proteins share little or no sequence similarity with other eukaryotes. This feature impairs the identification of important proteins participating in the regulation of the cell cycle. There are several open questions that concern cell cycle progression in malaria parasites, including the mechanism by which multiple nuclear divisions is co...

PRR11 regulates late-S to G2/M phase progression and induces premature chromatin condensation (PCC)

Energy Technology Data Exchange (ETDEWEB)

Zhang, Chundong; Zhang, Ying; Li, Yi; Zhu, Huifang; Wang, Yitao; Cai, Wei [Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016 (China); Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016 (China); Zhu, Jiang [Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016 (China); Ozaki, Toshinori [Laboratory of DNA Damage Signaling, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuohku, Chiba 260-8717 (Japan); Bu, Youquan, E-mail: buyqcn@aliyun.com [Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016 (China); Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016 (China)

2015-03-13

Recently, we have demonstrated that proline-rich protein 11 (PRR11) is a novel tumor-related gene product likely implicated in the regulation of cell cycle progression as well as lung cancer development. However, its precise role in cell cycle progression remains unclear. In the present study, we have further investigated the expression pattern and functional implication of PRR11 during cell cycle in detail in human lung carcinoma-derived H1299 cells. According to our immunofluorescence study, PRR11 was expressed largely in cytoplasm, the amount of PRR11 started to increase in the late S phase, and was retained until just before mitotic telophase. Consistent with those observations, siRNA-mediated knockdown of PRR11 caused a significant cell cycle arrest in the late S phase. Intriguingly, the treatment with dNTPs further augmented PRR11 silencing-mediated S phase arrest. Moreover, knockdown of PRR11 also resulted in a remarkable retardation of G2/M progression, and PRR11-knockdown cells subsequently underwent G2 phase cell cycle arrest accompanied by obvious mitotic defects such as multipolar spindles and multiple nuclei. In addition, forced expression of PRR11 promoted the premature Chromatin condensation (PCC), and then proliferation of PRR11-expressing cells was massively attenuated and induced apoptosis. Taken together, our current observations strongly suggest that PRR11, which is strictly regulated during cell cycle progression, plays a pivotal role in the regulation of accurate cell cycle progression through the late S phase to mitosis. - Highlights: • PRR11 started to increase in the late S phase and was retained until just before mitotic telophase. • PRR11-knockdown caused a significant cell cycle arrest in the late S phase and G2 phase. • The treatment with dNTPs further augmented PRR11 silencing-mediated S phase arrest. • PRR11-knockdown led to multipolar spindles and multiple nuclei. • Forced expression of PRR11 promoted the PCC and inhibited

PRR11 regulates late-S to G2/M phase progression and induces premature chromatin condensation (PCC)

International Nuclear Information System (INIS)

Zhang, Chundong; Zhang, Ying; Li, Yi; Zhu, Huifang; Wang, Yitao; Cai, Wei; Zhu, Jiang; Ozaki, Toshinori; Bu, Youquan

2015-01-01

Recently, we have demonstrated that proline-rich protein 11 (PRR11) is a novel tumor-related gene product likely implicated in the regulation of cell cycle progression as well as lung cancer development. However, its precise role in cell cycle progression remains unclear. In the present study, we have further investigated the expression pattern and functional implication of PRR11 during cell cycle in detail in human lung carcinoma-derived H1299 cells. According to our immunofluorescence study, PRR11 was expressed largely in cytoplasm, the amount of PRR11 started to increase in the late S phase, and was retained until just before mitotic telophase. Consistent with those observations, siRNA-mediated knockdown of PRR11 caused a significant cell cycle arrest in the late S phase. Intriguingly, the treatment with dNTPs further augmented PRR11 silencing-mediated S phase arrest. Moreover, knockdown of PRR11 also resulted in a remarkable retardation of G2/M progression, and PRR11-knockdown cells subsequently underwent G2 phase cell cycle arrest accompanied by obvious mitotic defects such as multipolar spindles and multiple nuclei. In addition, forced expression of PRR11 promoted the premature Chromatin condensation (PCC), and then proliferation of PRR11-expressing cells was massively attenuated and induced apoptosis. Taken together, our current observations strongly suggest that PRR11, which is strictly regulated during cell cycle progression, plays a pivotal role in the regulation of accurate cell cycle progression through the late S phase to mitosis. - Highlights: • PRR11 started to increase in the late S phase and was retained until just before mitotic telophase. • PRR11-knockdown caused a significant cell cycle arrest in the late S phase and G2 phase. • The treatment with dNTPs further augmented PRR11 silencing-mediated S phase arrest. • PRR11-knockdown led to multipolar spindles and multiple nuclei. • Forced expression of PRR11 promoted the PCC and inhibited

Dynamics of the cell-cycle network under genome-rewiring perturbations

International Nuclear Information System (INIS)

Katzir, Yair; Elhanati, Yuval; Braun, Erez; Averbukh, Inna

2013-01-01

The cell-cycle progression is regulated by a specific network enabling its ordered dynamics. Recent experiments supported by computational models have shown that a core of genes ensures this robust cycle dynamics. However, much less is known about the direct interaction of the cell-cycle regulators with genes outside of the cell-cycle network, in particular those of the metabolic system. Following our recent experimental work, we present here a model focusing on the dynamics of the cell-cycle core network under rewiring perturbations. Rewiring is achieved by placing an essential metabolic gene exclusively under the regulation of a cell-cycle's promoter, forcing the cell-cycle network to function under a multitasking challenging condition; operating in parallel the cell-cycle progression and a metabolic essential gene. Our model relies on simple rate equations that capture the dynamics of the relevant protein–DNA and protein–protein interactions, while making a clear distinction between these two different types of processes. In particular, we treat the cell-cycle transcription factors as limited ‘resources’ and focus on the redistribution of resources in the network during its dynamics. This elucidates the sensitivity of its various nodes to rewiring interactions. The basic model produces the correct cycle dynamics for a wide range of parameters. The simplicity of the model enables us to study the interface between the cell-cycle regulation and other cellular processes. Rewiring a promoter of the network to regulate a foreign gene, forces a multitasking regulatory load. The higher the load on the promoter, the longer is the cell-cycle period. Moreover, in agreement with our experimental results, the model shows that different nodes of the network exhibit variable susceptibilities to the rewiring perturbations. Our model suggests that the topology of the cell-cycle core network ensures its plasticity and flexible interface with other cellular processes

Human papillomavirus E6 and E7 oncoproteins alter cell cycle progression but not radiosensitivity of carcinoma cells treated with low-dose-rate radiation

International Nuclear Information System (INIS)

DeWeese, Theodore L.; Walsh, Jonathan C.; Dillehay, Larry E.; Kessis, Theodore D.; Hedrick, Lora; Cho, Kathleen R.; Nelson, William G.

1997-01-01

Purpose: Low-dose-rate radiation therapy has been widely used in the treatment of urogenital malignancies. When continuously exposed to low-dose-rate ionizing radiation, target cancer cells typically exhibit abnormalities in replicative cell-cycle progression. Cancer cells that arrest in the G2 phase of the cell cycle when irradiated may become exquisitely sensitive to killing by further low-dose-rate radiation treatment. Oncogenic human papillomaviruses (HPVs), which play a major role in the pathogenesis of uterine cervix cancers and other urogenital cancers, encode E6 and E7 transforming proteins known to abrogate a p53-dependent G1 cell-cycle checkpoint activated by conventional acute-dose radiation exposure. This study examined whether expression of HPV E6 and E7 oncoproteins by cancer cells alters the cell-cycle redistribution patterns accompanying low-dose-rate radiation treatment, and whether such alterations in cell-cycle redistribution affect cancer cell killing. Methods and Materials: RKO carcinoma cells, which contain wild-type P53 alleles, and RKO cell sublines genetically engineered to express HPV E6 and E7 oncoproteins, were treated with low-dose-rate (0.25-Gy/h) radiation and then assessed for p53 and p21WAF1/CIP1 polypeptide induction by immunoblot analysis, for cell-cycle redistribution by flow cytometry, and for cytotoxicity by clonogenic survival assay. Results: Low-dose-rate radiation of RKO carcinoma cells triggered p53 polypeptide elevations, p21WAF1/CIP1 induction, and arrest in the G1 and G2 phases of the cell cycle. In contrast, RKO cells expressing E6 and E7 transforming proteins from high-risk oncogenic HPVs (HPV 16) arrested in G2, but failed to arrest in G1, when treated with low-dose-rate ionizing radiation. Abrogation of the G1 cell-cycle checkpoint activated by low-dose-rate radiation exposure appeared to be a characteristic feature of transforming proteins from high-risk oncogenic HPVs: RKO cells expressing E6 from a low

Alanine-glyoxylate aminotransferase 2 (AGXT2 polymorphisms have considerable impact on methylarginine and β-aminoisobutyrate metabolism in healthy volunteers.

Directory of Open Access Journals (Sweden)

Anja Kittel

Full Text Available Elevated plasma concentrations of asymmetric (ADMA and symmetric (SDMA dimethylarginine have repeatedly been linked to adverse clinical outcomes. Both methylarginines are substrates of alanine-glyoxylate aminotransferase 2 (AGXT2. It was the aim of the present study to simultaneously investigate the functional relevance and relative contributions of common AGXT2 single nucleotide polymorphisms (SNPs to plasma and urinary concentrations of methylarginines as well as β-aminoisobutyrate (BAIB, a prototypic substrate of AGXT2. In a cohort of 400 healthy volunteers ADMA, SDMA and BAIB concentrations were determined in plasma and urine using HPLC-MS/MS and were related to the coding AGXT2 SNPs rs37369 (p.Val140Ile and rs16899974 (p.Val498Leu. Volunteers heterozygous or homozygous for the AGXT2 SNP rs37369 had higher SDMA plasma concentrations by 5% and 20% (p = 0.002 as well as higher BAIB concentrations by 54% and 146%, respectively, in plasma and 237% and 1661%, respectively, in urine (both p<0.001. ADMA concentrations were not affected by both SNPs. A haplotype analysis revealed that the second investigated AGXT2 SNP rs16899974, which was not significantly linked to the other AGXT2 SNP, further aggravates the effect of rs37369 with respect to BAIB concentrations in plasma and urine. To investigate the impact of the amino acid exchange p.Val140Ile, we established human embryonic kidney cell lines stably overexpressing wild-type or mutant (p.Val140Ile AGXT2 protein and assessed enzyme activity using BAIB and stable-isotope labeled [²H₆]-SDMA as substrate. In vitro, the amino acid exchange of the mutant protein resulted in a significantly lower enzyme activity compared to wild-type AGXT2 (p<0.05. In silico modeling of the SNPs indicated reduced enzyme stability and substrate binding. In conclusion, SNPs of AGXT2 affect plasma as well as urinary BAIB and SDMA concentrations linking methylarginine metabolism to the common genetic trait of hyper

Analysis within the systems development life-cycle

CERN Document Server

Rock-Evans, Rosemary

1987-01-01

Analysis within the Systems Development Life-Cycle: Book 2, Data Analysis-The Methods describes the methods for carrying out data analysis within the systems development life-cycle and demonstrates how the results of fact gathering can be used to produce and verify the analysis deliverables. A number of alternative methods of analysis other than normalization are suggested. Comprised of seven chapters, this book shows the tasks to be carried out in the logical order of progression-preparation, collection, analysis of the existing system (which comprises the tasks of synthesis, verification, an

2-Aminopurine overrides multiple cell cycle checkpoints in BHK cells.

OpenAIRE

Andreassen, P R; Margolis, R L

1992-01-01

BHK cells blocked at any of several points in the cell cycle override their drug-induced arrest and proceed in the cycle when exposed concurrently to the protein kinase inhibitor 2-aminopurine (2-AP). For cells arrested at various points in interphase, 2-AP-induced cell cycle progression is made evident by arrival of the drug-treated cell population in mitosis. Cells that have escaped from mimosine G1 arrest, from hydroxyurea or aphidicolin S-phase arrest, or from VM-26-induced G2 arrest subs...

The Manuel Lujan Jr. Neutron Scattering Center (LANSCE) experiment reports 1993 run cycle. Progress report

Energy Technology Data Exchange (ETDEWEB)

Farrer, R.; Longshore, A. [comps.

1995-06-01

This year the Manuel Lujan Jr. Neutron Scattering Center (LANSCE) ran an informal user program because the US Department of Energy planned to close LANSCE in FY1994. As a result, an advisory committee recommended that LANSCE scientists and their collaborators complete work in progress. At LANSCE, neutrons are produced by spallation when a pulsed, 800-MeV proton beam impinges on a tungsten target. The proton pulses are provided by the Clinton P. Anderson Meson Physics Facility (LAMPF) accelerator and a associated Proton Storage Ring (PSR), which can Iter the intensity, time structure, and repetition rate of the pulses. The LAMPF protons of Line D are shared between the LANSCE target and the Weapons Neutron Research (WNR) facility, which results in LANSCE spectrometers being available to external users for unclassified research about 80% of each annual LAMPF run cycle. Measurements of interest to the Los Alamos National Laboratory (LANL) may also be performed and may occupy up to an additional 20% of the available beam time. These experiments are reviewed by an internal program advisory committee. This year, a total of 127 proposals were submitted. The proposed experiments involved 229 scientists, 57 of whom visited LANSCE to participate in measurements. In addition, 3 (nuclear physics) participating research teams, comprising 44 scientists, carried out experiments at LANSCE. Instrument beam time was again oversubscribed, with 552 total days requested an 473 available for allocation.

The Manuel Lujan Jr. Neutron Scattering Center (LANSCE) experiment reports 1993 run cycle. Progress report

International Nuclear Information System (INIS)

Farrer, R.; Longshore, A.

1995-06-01

This year the Manuel Lujan Jr. Neutron Scattering Center (LANSCE) ran an informal user program because the US Department of Energy planned to close LANSCE in FY1994. As a result, an advisory committee recommended that LANSCE scientists and their collaborators complete work in progress. At LANSCE, neutrons are produced by spallation when a pulsed, 800-MeV proton beam impinges on a tungsten target. The proton pulses are provided by the Clinton P. Anderson Meson Physics Facility (LAMPF) accelerator and a associated Proton Storage Ring (PSR), which can Iter the intensity, time structure, and repetition rate of the pulses. The LAMPF protons of Line D are shared between the LANSCE target and the Weapons Neutron Research (WNR) facility, which results in LANSCE spectrometers being available to external users for unclassified research about 80% of each annual LAMPF run cycle. Measurements of interest to the Los Alamos National Laboratory (LANL) may also be performed and may occupy up to an additional 20% of the available beam time. These experiments are reviewed by an internal program advisory committee. This year, a total of 127 proposals were submitted. The proposed experiments involved 229 scientists, 57 of whom visited LANSCE to participate in measurements. In addition, 3 (nuclear physics) participating research teams, comprising 44 scientists, carried out experiments at LANSCE. Instrument beam time was again oversubscribed, with 552 total days requested an 473 available for allocation

Mineral cycling in soil and litter arthropod food chains. Progress report, 1985

International Nuclear Information System (INIS)

Crossley, D.A. Jr.

1985-01-01

Research progress in the following areas is briefly summarized: (1) microarthropod effects on microbial immobilization of nutrients during decomposition; and (2) effects of arthropods on decomposition rates of unconfined leaf litter

The use of solvent extraction in the nuclear fuel cycle, forty years of progress

International Nuclear Information System (INIS)

Germain, M.

1990-01-01

The high degree of purity required for the fissile and fertile elements used as fuels in nuclear reactors has made solvent extraction the choice as the purification method in the different steps of the fuel cycle. This technique, owing to its specificity, and its adaptability both to continuous multistage processes and to remote control, has served to achieve the requisite purities with safe, reliable operation. A review of the different steps of the cycle including uranium and thorium production, uranium enrichment, reprocessing, and the recovery of transuranics, highlights the diversity of the solvents used and the improvements made to the processes and the equipment. According to the different authors, this technique is capable of meeting future needs, aimed to reduce the harmful effects associated with the nuclear fuel cycle to the lowest possible levels

Cell cycle-dependent activity of the volume- and Ca2+-activated anion currents in Ehrlich lettre ascites cells

DEFF Research Database (Denmark)

Klausen, Thomas Kjaer; Bergdahl, Andreas; Christophersen, Palle

2007-01-01

Recent evidence implicates the volume-regulated anion current (VRAC) and other anion currents in control or modulation of cell cycle progression; however, the precise involvement of anion channels in this process is unclear. Here, Cl- currents in Ehrlich Lettre Ascites (ELA) cells were monitored...... during cell cycle progression, under three conditions: (i) after osmotic swelling (i.e., VRAC), (ii) after an increase in the free intracellular Ca2+ concentration (i.e., the Ca2+-activated Cl- current, CaCC), and (iii) under steady-state isotonic conditions. The maximal swelling-activated VRAC current......+ in the pipette), was unaltered from G0 to G1, but decreased in early S phase. A novel high-affinity anion channel inhibitor, the acidic di-aryl-urea NS3728, which inhibited both VRAC and CaCC, attenuated ELA cell growth, suggesting a possible mechanistic link between cell cycle progression and cell cycle...

Chemical Engineering Division Fuel Cycle Programs. Quarterly progress report, October-December 1981

International Nuclear Information System (INIS)

Steindler, M.J.; Bates, J.K.; Cannon, T.F.

1982-05-01

Methods of measuring rates of leaching from simulated waste glasses using neutron activation analysis and radiotracers have been developed. Laboratory-scale impact tests of solid alternative waste forms are being performed to obtain a size analysis of the fragments. Logging techniques are being developed to measure the relative amount of residual oil in a depleted oil reservoir by injecting gamma-active solution into it. Work to test the behavior of radionuclides leached from proposed nuclear-waste repositories using laboratory-analog experiments is in progress. High potassium levels in crushed granite from a Northern Illinois drill hole are probably derived by the leaching of potassium feldspar. Testing and development of equipment for the destructive analysis of full-length irradiated fuel rods from the LWBR are in progress. 19 figures, 13 tables

SUMO-modified insulin-like growth factor 1 receptor (IGF-1R) increases cell cycle progression and cell proliferation.

Science.gov (United States)

Lin, Yingbo; Liu, Hongyu; Waraky, Ahmed; Haglund, Felix; Agarwal, Prasoon; Jernberg-Wiklund, Helena; Warsito, Dudi; Larsson, Olle

2017-10-01

Increasing number of studies have shown nuclear localization of the insulin-like growth factor 1 receptor (nIGF-1R) in tumor cells and its links to adverse clinical outcome in various cancers. Any obvious cell physiological roles of nIGF-1R have, however, still not been disclosed. Previously, we reported that IGF-1R translocates to cell nucleus and modulates gene expression by binding to enhancers, provided that the receptor is SUMOylated. In this study, we constructed stable transfectants of wild type IGF1R (WT) and triple-SUMO-site-mutated IGF1R (TSM) using igf1r knockout mouse fibroblasts (R-). Cell clones (R-WT and R-TSM) expressing equal amounts of IGF-1R were selected for experiments. Phosphorylation of IGF-1R, Akt, and Erk upon IGF-1 stimulation was equal in R-WT and R-TSM. WT was confirmed to enter nuclei. TSM did also undergo nuclear translocation, although to a lesser extent. This may be explained by that TSM heterodimerizes with insulin receptor, which is known to translocate to cell nuclei. R-WT proliferated substantially faster than R-TSM, which did not differ significantly from the empty vector control. Upon IGF-1 stimulation G1-S-phase progression of R-WT increased from 12 to 38%, compared to 13 to 20% of R-TSM. The G1-S progression of R-WT correlated with increased expression of cyclin D1, A, and CDK2, as well as downregulation of p27. This suggests that SUMO-IGF-1R affects upstream mechanisms that control and coordinate expression of cell cycle regulators. Further studies to identify such SUMO-IGF-1R dependent mechanisms seem important. © 2017 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals Inc.

Advanced-ORIENT cycle, its scientific progress and prospect for engineering feasibility

International Nuclear Information System (INIS)

Koyama, Shin-ichi; Yamagishi, Isao; Fujii, Yasuhiko; Suzuki, Tatsuya; Ozawa, Masaki; Fujita, Reiko; Okada, Ken; Tatenuma, Katsuyoshi; Mimura, Hitoshi

2011-01-01

For the ultimate minimization of the ecological risks originated in nuclear fuel recycling, a new fuel cycle paradigm was proposed and the basic researches have been carried out as a first phase under the Adv.-ORIENT (Advanced Optimization by Recycling Instructive Elements) Cycle project. In this paradigm, effective separation of actinide (An) and long lived-fission product (LLFP), transmutation of An, utilization of separated nuclides, such as lanthanides (Lns) and platinum group metals (PGM), were the main directions. In such directions, tertiary pyridine-type resin (TPR) enabled to separate minor actinide (MA)/Ln and then Am/Cm precisely from spent fuel, provided permitting to use HCl as well as and HNO 3 media. Recovery of very pure Am and Cm products could be done in this phase. The PGM and Tc separation; Catalytic electrolytic extraction (CEE) method could effectively separate the light PGM ,Tc from HCl and HNO 3 media, especially by HCl media. The PGM and Tc utilization; Mixed deposit obtained from the CEE experiments, Ru/Rh/Pd/Tc(Re)-Pt electrodes indicated the highest catalytic reactivity on electrolytic production of hydrogen in an alkali solution. Recovery of Cs from simulated spent fuel solution by silica gel loaded with ammonium molybdophosphate (AMP) was carried out, and the uptake rate achieved more than 90%. Separated Cs is expected to utilize as a heat source element. As basic engineering research efforts, some candidate metals, such as Ta, Nb, Zr and Hastelloy-B (Ni-28Mo), were examined to confirm an anti-corrosive property in wide HCl environment. Gram scale experiment to identify a thermo-chemical stability of TPR and TBP (as a reference) was also performed experimentally, and process safety conditions could be found out for its practical use. In this paper, study for each integrant technology was concluded as first trial of Adv.-ORIENT Cycle project, and the perspective for next phase was proposed. (author)

Real-time tracking of cell cycle progression during CD8+ effector and memory T-cell differentiation.

Science.gov (United States)

Kinjyo, Ichiko; Qin, Jim; Tan, Sioh-Yang; Wellard, Cameron J; Mrass, Paulus; Ritchie, William; Doi, Atsushi; Cavanagh, Lois L; Tomura, Michio; Sakaue-Sawano, Asako; Kanagawa, Osami; Miyawaki, Atsushi; Hodgkin, Philip D; Weninger, Wolfgang

2015-02-24

The precise pathways of memory T-cell differentiation are incompletely understood. Here we exploit transgenic mice expressing fluorescent cell cycle indicators to longitudinally track the division dynamics of individual CD8(+) T cells. During influenza virus infection in vivo, naive T cells enter a CD62L(intermediate) state of fast proliferation, which continues for at least nine generations. At the peak of the anti-viral immune response, a subpopulation of these cells markedly reduces their cycling speed and acquires a CD62L(hi) central memory cell phenotype. Construction of T-cell family division trees in vitro reveals two patterns of proliferation dynamics. While cells initially divide rapidly with moderate stochastic variations of cycling times after each generation, a slow-cycling subpopulation displaying a CD62L(hi) memory phenotype appears after eight divisions. Phenotype and cell cycle duration are inherited by the progeny of slow cyclers. We propose that memory precursors cell-intrinsically modulate their proliferative activity to diversify differentiation pathways.

Alternative energies. Updates on progress

Energy Technology Data Exchange (ETDEWEB)

Ferreira, German (ed.) [CIRCE - Centre of Research for Energy Resources and Consumption, Zaragoza (Spain)

2013-07-01

Presents fundamental and applied research of alternative energies. Address key pillars in the alternative energy field, such as: biomass energy, hydrogen energy, solar energy, wind energy, hydroelectric power, geothermal energy and their environmental implications, with the most updated progress. Includes the life cycle assessment and thermoeconomic analysis as tools for evaluating and optimising environmental and cost subjects. This book presents nine chapters based on fundamental and applied research of alternative energies. At the present time, the challenge is that technology has to come up with solutions that can provide environmentally friendly energy supply options that are able to cover the current world energy demand. Experts around the world are working on these issues for providing new solutions that will break the existing technological barriers. This book aims to address key pillars in the alternative energy field, such as: biomass energy, hydrogen energy, solar energy, wind energy, hydroelectric power, geothermal energy and their environmental implications, with the most updated progress for each pillar. It also includes the life cycle assessment (LCA) and thermoeconomic analysis (TA) as tools for evaluating and optimising environmental and cost subjects. Chapters are organized into fundamental research, applied research and future trends; and written for engineers, academic researches and scientists.

Multiparameter Cell Cycle Analysis.

Science.gov (United States)

Jacobberger, James W; Sramkoski, R Michael; Stefan, Tammy; Woost, Philip G

2018-01-01

Cell cycle cytometry and analysis are essential tools for studying cells of model organisms and natural populations (e.g., bone marrow). Methods have not changed much for many years. The simplest and most common protocol is DNA content analysis, which is extensively published and reviewed. The next most common protocol, 5-bromo-2-deoxyuridine S phase labeling detected by specific antibodies, is also well published and reviewed. More recently, S phase labeling using 5'-ethynyl-2'-deoxyuridine incorporation and a chemical reaction to label substituted DNA has been established as a basic, reliable protocol. Multiple antibody labeling to detect epitopes on cell cycle regulated proteins, which is what this chapter is about, is the most complex of these cytometric cell cycle assays, requiring knowledge of the chemistry of fixation, the biochemistry of antibody-antigen reactions, and spectral compensation. However, because this knowledge is relatively well presented methodologically in many papers and reviews, this chapter will present a minimal Methods section for one mammalian cell type and an extended Notes section, focusing on aspects that are problematic or not well described in the literature. Most of the presented work involves how to segment the data to produce a complete, progressive, and compartmentalized cell cycle analysis from early G1 to late mitosis (telophase). A more recent development, using fluorescent proteins fused with proteins or peptides that are degraded by ubiquitination during specific periods of the cell cycle, termed "Fucci" (fluorescent, ubiquitination-based cell cycle indicators) provide an analysis similar in concept to multiple antibody labeling, except in this case cells can be analyzed while living and transgenic organisms can be created to perform cell cycle analysis ex or in vivo (Sakaue-Sawano et al., Cell 132:487-498, 2007). This technology will not be discussed.

Protein tyrosine nitration in the cell cycle

International Nuclear Information System (INIS)

Jia, Min; Mateoiu, Claudia; Souchelnytskyi, Serhiy

2011-01-01

Highlights: → Enrichment of 3-nitrotyrosine containing proteins from cells synchronized in different phases of the cell cycle. → Identification of 76 tyrosine nitrated proteins that change expression during the cell cycle. → Nineteen identified proteins were previously described as regulators of cell proliferation. -- Abstract: Nitration of tyrosine residues in proteins is associated with cell response to oxidative/nitrosative stress. Tyrosine nitration is relatively low abundant post-translational modification that may affect protein functions. Little is known about the extent of protein tyrosine nitration in cells during progression through the cell cycle. Here we report identification of proteins enriched for tyrosine nitration in cells synchronized in G0/G1, S or G2/M phases of the cell cycle. We identified 27 proteins in cells synchronized in G0/G1 phase, 37 proteins in S phase synchronized cells, and 12 proteins related to G2/M phase. Nineteen of the identified proteins were previously described as regulators of cell proliferation. Thus, our data indicate which tyrosine nitrated proteins may affect regulation of the cell cycle.

Do lipids shape the eukaryotic cell cycle?

Science.gov (United States)

Furse, Samuel; Shearman, Gemma C

2018-01-01

Successful passage through the cell cycle presents a number of structural challenges to the cell. Inceptive studies carried out in the last five years have produced clear evidence of modulations in the lipid profile (sometimes referred to as the lipidome) of eukaryotes as a function of the cell cycle. This mounting body of evidence indicates that lipids play key roles in the structural transformations seen across the cycle. The accumulation of this evidence coincides with a revolution in our understanding of how lipid composition regulates a plethora of biological processes ranging from protein activity through to cellular signalling and membrane compartmentalisation. In this review, we discuss evidence from biological, chemical and physical studies of the lipid fraction across the cell cycle that demonstrate that lipids are well-developed cellular components at the heart of the biological machinery responsible for managing progress through the cell cycle. Furthermore, we discuss the mechanisms by which this careful control is exercised. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

The LifeCycle model

DEFF Research Database (Denmark)

Krink, Thiemo; Løvbjerg, Morten

2002-01-01

genetic algorithms (GAs), particle swarm optimisation (PSOs), and stochastic hill climbing to create a generally well-performing search heuristics. In the LifeCycle model, we consider candidate solutions and their fitness as individuals, which, based on their recent search progress, can decide to become...... either a GA individual, a particle of a PSO, or a single stochastic hill climber. First results from a comparison of our new approach with the single search algorithms indicate a generally good performance in numerical optimization....

Phase II trial of pazopanib in advanced/progressive malignant pheochromocytoma and paraganglioma.

Science.gov (United States)

Jasim, Sina; Suman, Vera J; Jimenez, Camilo; Harris, Pamela; Sideras, Kostandinos; Burton, Jill K; Worden, Francis Paul; Auchus, Richard J; Bible, Keith C

2017-08-01

Pheochromocytomas and paragangliomas (Pheo/PGL) are rare, vascular, sometimes malignant endocrine tumors. Case reports indicate the activity of vascular endothelium growth factor receptor-targeted kinase inhibitors in these cancers. To assess the antitumor activity and tolerability of pazopanib in progressive malignant Pheo/PGL. This multicenter Phase II trial (MC107C) enrolled individuals  ≥18 years old with disease progression ≤ 6 months prior to registration, Eastern Cooperative Oncology Group PS 0-2, and measurable disease (response evaluation criteria in solid tumors 1.0). Pazopanib was administered in 28-day cycles, with the regimen ultimately being as follows: cycle 1: 400 mg daily on days 1-14, cycle 2: 800 mg daily on days 1-14, and then cycle 2 + : 800 mg daily on all days. The study was halted due to poor accrual. Seven patients were enrolled (05/2011-11/2014). One patient withdrew consent prior to treatment, leaving six evaluable patients. Treatment was discontinued, due to the following reasons: disease progression (4); withdrawal (1); and grade 4 (Takotsubo) cardiomyopathy (1). The median number of cycles administered was 4 (range: 2-29, total: 49). Four patients had >1 dose reduction due to the following reasons: fatigue (1), abnormal liver tests (2), hypertension and (Takotsubo) cardiomyopathy (1), and headaches (1). Common severe (Common Terminology Criteria for Adverse Events v3.0 grades 3-5) toxicities were as follows: hypertension (3/6), (Takotsubo) cardiomyopathy (2/6), diarrhea (1/6), fatigue (1/6), headache (1/6), and hematuria (1/6). One confirmed partial response was observed in PGL (17%, duration 2.4 years); median progression-free survival and overall survival were 6.5 and 14.8 months, respectively. Pazopanib has activity in Pheo/PGL requiring more study; optimal alpha- and beta-blockade are imperative pre-therapy in patients with secretory tumors, as risk of hypertension and cardiomyopathy are potentially life

Characteristics of fuel cycle waste

International Nuclear Information System (INIS)

Aquilina, C.A.; Everette, S.E.

1982-01-01

The Low-Level Waste Management System started in 1979 to describe and model the existing commercial low-level waste management system. The system description produced is based on the identification of the different elements making up both the fuel and non-fuel cycle and their relationships to each other. A systems model based on the system description can accurately reflect the flow of low-level waste from generator to disposal site and is only limited by the reliability of the information it uses. For both the fuel cycle and non-fuel cycle large quantities of information is required in order to allow the system to operate at its full potential. Work is ongoing to collect this information. Significant progress is being made in the fuel cycle area primarily because the majority of fuel cycle low-level radioactive waste is produced by commercial power reactor plant operations. The Low-Level Waste Management system is only beginning to derive the benefits to be obtained from an accurate low-level waste management information system. As data is verified and analyzed, results on a national as well as individual organization level will be gained. Comparisons to previous studies will be made. Accurate projections of waste volumes and activities to be produced, projected impacts of waste streams of treatment or management changes are only examples of information to be produced. 1 figure, 1 table

Co-ordinate regulation of genes involved in storage lipid mobilization in Arabidopsis thaliana.

Science.gov (United States)

Rylott, E L; Hooks, M A; Graham, I A

2001-05-01

Molecular genetic approaches in the model plant Arabidopsis thaliana (Col0) are shedding new light on the role and control of the pathways associated with the mobilization of lipid reserves during oilseed germination and post-germinative growth. Numerous independent studies have reported on the expression of individual genes encoding enzymes from the three major pathways: beta-oxidation, the glyoxylate cycle and gluconeogenesis. However, a single comprehensive study of representative genes and enzymes from the different pathways in a single plant species has not been done. Here we present results from Arabidopsis that demonstrate the co-ordinate regulation of gene expression and enzyme activities for the acyl-CoA oxidase- and 3-ketoacyl-CoA thiolase-mediated steps of beta-oxidation, the isocitrate lyase and malate synthase steps of the glyoxylate cycle and the phosphoenolpyruvate carboxykinase step of gluconeogenesis. The mRNA abundance and enzyme activities increase to a peak at stage 2, 48 h after the onset of seed germination, and decline thereafter either to undetectable levels (for malate synthase and isocitrate lyase) or low basal levels (for the genes of beta-oxidation and gluconeogenesis). The co-ordinate induction of all these genes at the onset of germination raises the possibility that a global regulatory mechanism operates to induce the expression of genes associated with the mobilization of storage reserves during the heterotrophic growth period.

Directing vanillin production from ferulic acid by increased acetyl-CoA consumption in recombinant Escherichia coli.

Science.gov (United States)

Lee, Eun-Gyeong; Yoon, Sang-Hwal; Das, Amitabha; Lee, Sook-Hee; Li, Cui; Kim, Jae-Yean; Choi, Myung-Suk; Oh, Deok-Kun; Kim, Seon-Won

2009-01-01

The amplification of gltA gene encoding citrate synthase of TCA cycle was required for the efficient conversion of acetyl-CoA, generated during vanillin production from ferulic acid, to CoA, which is essential for vanillin production. Vanillin of 1.98 g/L was produced from the E. coli DH5alpha (pTAHEF-gltA) with gltA amplification in 48 h of culture at 3.0 g/L of ferulic acid, which was about twofold higher than the vanillin production of 0.91 g/L obtained by the E. coli DH5alpha (pTAHEF) without gltA amplification. The icdA gene encoding isocitrate dehydrogenase of TCA cycle was deleted to make the vanillin producing E. coli utilize glyoxylate bypass which enables more efficient conversion of acetyl-CoA to CoA in comparison with TCA cycle. The production of vanillin by the icdA null mutant of E. coli BW25113 harboring pTAHEF was enhanced by 2.6 times. The gltA amplification of the glyoxylate bypass in the icdA null mutant remarkably increased the production rate of vanillin with a little increase in the amount of vanillin production. The real synergistic effect of gltA amplification and icdA deletion was observed with use of XAD-2 resin reducing the toxicity of vanillin produced during culture. Vanillin of 5.14 g/L was produced in 24 h of the culture with molar conversion yield of 86.6%, which is the highest so far in vanillin production from ferulic acid using recombinant E. coli.

Estrogen receptor alpha is cell cycle-regulated and regulates the cell cycle in a ligand-dependent fashion.

Science.gov (United States)

JavanMoghadam, Sonia; Weihua, Zhang; Hunt, Kelly K; Keyomarsi, Khandan

2016-06-17

Estrogen receptor alpha (ERα) has been implicated in several cell cycle regulatory events and is an important predictive marker of disease outcome in breast cancer patients. Here, we aimed to elucidate the mechanism through which ERα influences proliferation in breast cancer cells. Our results show that ERα protein is cell cycle-regulated in human breast cancer cells and that the presence of 17-β-estradiol (E2) in the culture medium shortened the cell cycle significantly (by 4.5 hours, P cycle duration were observed in the S and G2/M phases, whereas the G1 phase was indistinguishable under liganded and unliganded conditions. In addition, ERα knockdown in MCF-7 cells accelerated mitotic exit, whereas transfection of ERα-negative MDA-MB-231 cells with exogenous ERα significantly shortened the S and G2/M phases (by 9.1 hours, P cycle progression through the S and G2/M phases than fulvestrant does, presumably because of the destabilizing effect of fulvestrant on ERα protein. Together, these results show that ERα modulates breast cancer cell proliferation by regulating events during the S and G2/M phases of the cell cycle in a ligand-dependent fashion. These results provide the rationale for an effective treatment strategy that includes a cell cycle inhibitor in combination with a drug that lowers estrogen levels, such as an aromatase inhibitor, and an antiestrogen that does not result in the degradation of ERα, such as tamoxifen.

Quantitative Cell Cycle Analysis Based on an Endogenous All-in-One Reporter for Cell Tracking and Classification

Directory of Open Access Journals (Sweden)

Thomas Zerjatke

2017-05-01

Full Text Available Cell cycle kinetics are crucial to cell fate decisions. Although live imaging has provided extensive insights into this relationship at the single-cell level, the limited number of fluorescent markers that can be used in a single experiment has hindered efforts to link the dynamics of individual proteins responsible for decision making directly to cell cycle progression. Here, we present fluorescently tagged endogenous proliferating cell nuclear antigen (PCNA as an all-in-one cell cycle reporter that allows simultaneous analysis of cell cycle progression, including the transition into quiescence, and the dynamics of individual fate determinants. We also provide an image analysis pipeline for automated segmentation, tracking, and classification of all cell cycle phases. Combining the all-in-one reporter with labeled endogenous cyclin D1 and p21 as prime examples of cell-cycle-regulated fate determinants, we show how cell cycle and quantitative protein dynamics can be simultaneously extracted to gain insights into G1 phase regulation and responses to perturbations.

Hamster activity and estrous cycles: control by a single versus multiple circadian oscillator(s).

OpenAIRE

Carmichael, M S; Nelson, R J; Zucker, I

1981-01-01

Running activity onset and estrous onset were recorded for hamsters exposed to progressively shorter daily light/dark (T) cycles. The period of the estrous cycle was a quadruple multiple of the period of the activity rhythm during entrainment to T cycles of 23.5-21.5 hr. There was no evidence of desynchronization of the activity and estrus rhythms. The very short estrous periods shown during exposure to short T cycles indicate that an intrinsic 96-hr interval for ovarian follicular maturation...

Updates on Modeling the Water Cycle with the NASA Ames Mars Global Climate Model

Science.gov (United States)

Kahre, M. A.; Haberle, R. M.; Hollingsworth, J. L.; Montmessin, F.; Brecht, A. S.; Urata, R.; Klassen, D. R.; Wolff, M. J.

2017-01-01

Global Circulation Models (GCMs) have made steady progress in simulating the current Mars water cycle. It is now widely recognized that clouds are a critical component that can significantly affect the nature of the simulated water cycle. Two processes in particular are key to implementing clouds in a GCM: the microphysical processes of formation and dissipation, and their radiative effects on heating/ cooling rates. Together, these processes alter the thermal structure, change the dynamics, and regulate inter-hemispheric transport. We have made considerable progress representing these processes in the NASA Ames GCM, particularly in the presence of radiatively active water ice clouds. We present the current state of our group's water cycle modeling efforts, show results from selected simulations, highlight some of the issues, and discuss avenues for further investigation.­

Redox Changes During the Cell Cycle in the Embryonic Root Meristem of Arabidopsis thaliana.

Science.gov (United States)

de Simone, Ambra; Hubbard, Rachel; de la Torre, Natanael Viñegra; Velappan, Yazhini; Wilson, Michael; Considine, Michael J; Soppe, Wim J J; Foyer, Christine H

2017-12-20

The aim of this study was to characterize redox changes in the nuclei and cytosol occurring during the mitotic cell cycle in the embryonic roots of germinating Arabidopsis seedlings, and to determine how redox cycling was modified in mutants with a decreased capacity for ascorbate synthesis. Using an in vivo reduction-oxidation (redox) reporter (roGFP2), we show that transient oxidation of the cytosol and the nuclei occurred at G1 in the synchronized dividing cells of the Arabidopsis root apical meristem, with reduction at G2 and mitosis. This redox cycle was absent from low ascorbate mutants in which nuclei were significantly more oxidized than controls. The cell cycle-dependent increase in nuclear size was impaired in the ascorbate-deficient mutants, which had fewer cells per unit area in the root proliferation zone. The transcript profile of the dry seeds and size of the imbibed seeds was strongly influenced by low ascorbate but germination, dormancy release and seed aging characteristics were unaffected. These data demonstrate the presence of a redox cycle within the plant cell cycle and that the redox state of the nuclei is an important factor in cell cycle progression. Controlled oxidation is a key feature of the early stages of the plant cell cycle. However, sustained mild oxidation restricts nuclear functions and impairs progression through the cell cycle leading to fewer cells in the root apical meristem. Antioxid. Redox Signal. 27, 1505-1519.

Fuel cycles using adulterated plutonium

International Nuclear Information System (INIS)

Brooksbank, R.E.; Bigelow, J.E.; Campbell, D.O.; Kitts, F.G.; Lindauer, R.B.

1978-01-01

Adjustments in the U-Pu fuel cycle necessitated by decisions made to improve the nonproliferation objectives of the US are examined. The uranium-based fuel cycle, using bred plutonium to provide the fissile enrichment, is the fuel system with the highest degree of commercial development at the present time. However, because purified plutonium can be used in weapons, this fuel cycle is potentially vulnerable to diversion of that plutonium. It does appear that there are technologically sound ways in which the plutonium might be adulterated by admixture with 238 U and/or radioisotopes, and maintained in that state throughout the fuel cycle, so that the likelihood of a successful diversion is small. Adulteration of the plutonium in this manner would have relatively little effect on the operations of existing or planned reactors. Studies now in progress should show within a year or two whether the less expensive coprocessing scheme would provide adequate protection (coupled perhaps with elaborate conventional safeguards procedures) or if the more expensive spiked fuel cycle is needed as in the proposed civex pocess. If the latter is the case, it will be further necessary to determine the optimum spiking level, which could vary as much as a factor of a billion. A very basic question hangs on these determinations: What is to be the nature of the recycle fuel fabrication facilities. If the hot, fully remote fuel fabrication is required, then a great deal of further development work will be required to make the full cycle fully commercial

Discovery of a Splicing Regulator Required for Cell Cycle Progression

Energy Technology Data Exchange (ETDEWEB)

Suvorova, Elena S.; Croken, Matthew; Kratzer, Stella; Ting, Li-Min; Conde de Felipe, Magnolia; Balu, Bharath; Markillie, Lye Meng; Weiss, Louis M.; Kim, Kami; White, Michael W.

2013-02-01

In the G1 phase of the cell division cycle, eukaryotic cells prepare many of the resources necessary for a new round of growth including renewal of the transcriptional and protein synthetic capacities and building the machinery for chromosome replication. The function of G1 has an early evolutionary origin and is preserved in single and multicellular organisms, although the regulatory mechanisms conducting G1 specific functions are only understood in a few model eukaryotes. Here we describe a new G1 mutant from an ancient family of apicomplexan protozoans. Toxoplasma gondii temperature-sensitive mutant 12-109C6 conditionally arrests in the G1 phase due to a single point mutation in a novel protein containing a single RNA-recognition-motif (TgRRM1). The resulting tyrosine to asparagine amino acid change in TgRRM1 causes severe temperature instability that generates an effective null phenotype for this protein when the mutant is shifted to the restrictive temperature. Orthologs of TgRRM1 are widely conserved in diverse eukaryote lineages, and the human counterpart (RBM42) can functionally replace the missing Toxoplasma factor. Transcriptome studies demonstrate that gene expression is downregulated in the mutant at the restrictive temperature due to a severe defect in splicing that affects both cell cycle and constitutively expressed mRNAs. The interaction of TgRRM1 with factors of the tri-SNP complex (U4/U6 & U5 snRNPs) indicate this factor may be required to assemble an active spliceosome. Thus, the TgRRM1 family of proteins is an unrecognized and evolutionarily conserved class of splicing regulators. This study demonstrates investigations into diverse unicellular eukaryotes, like the Apicomplexa, have the potential to yield new insights into important mechanisms conserved across modern eukaryotic kingdoms.

Emissions from photovoltaic life cycles.

Science.gov (United States)

Fthenakis, Vasilis M; Kim, Hyung Chul; Alsema, Erik

2008-03-15

Photovoltaic (PV) technologies have shown remarkable progress recently in terms of annual production capacity and life cycle environmental performances, which necessitate timely updates of environmental indicators. Based on PV production data of 2004-2006, this study presents the life-cycle greenhouse gas emissions, criteria pollutant emissions, and heavy metal emissions from four types of major commercial PV systems: multicrystalline silicon, monocrystalline silicon, ribbon silicon, and thin-film cadmium telluride. Life-cycle emissions were determined by employing average electricity mixtures in Europe and the United States during the materials and module production for each PV system. Among the current vintage of PV technologies, thin-film cadmium telluride (CdTe) PV emits the least amount of harmful air emissions as it requires the least amount of energy during the module production. However, the differences in the emissions between different PV technologies are very small in comparison to the emissions from conventional energy technologies that PV could displace. As a part of prospective analysis, the effect of PV breeder was investigated. Overall, all PV technologies generate far less life-cycle air emissions per GWh than conventional fossil-fuel-based electricity generation technologies. At least 89% of air emissions associated with electricity generation could be prevented if electricity from photovoltaics displaces electricity from the grid.

LMFBR fuel cycle studies progress report, August 1972, No. 42

International Nuclear Information System (INIS)

Unger, W.E.; Blanco, R.E.; Crouse, D.J.; Irvine, A.R.; Watson, C.D.

1972-10-01

This report continues a series outlining progress in the development of methods for reprocessing of LMFBR fuels. Development work is reported on problems of irradiated fuel transport to the processing facility, the dissolution of the fuel and the chemical recovery of PuO 2 --UO 2 values, the containment of volatile fission products, product purification, conversion of fuel processing plant product nitrate solutions to solids suitable for shipping and for subsequent fuel fabrication. Pertinent experimental results are presented for the information of those immediately concerned with the field. Detailed description of experimental work and data are included in the topical reports and in the Chemical Technology Division Annual Reports

Research reactors fuel cycle problems and dilemma

International Nuclear Information System (INIS)

Romano, R.

2004-01-01

During last 10 years, some problems appeared in different steps of research reactors fuel cycle. Actually the majority of these reactors have been built in the 60s and these reactors were operated during all this long period in a cycle with steps which were dedicated to this activity. Progressively and for reasons often economical, certain steps of the cycle became more and more difficult to manage due to closing of some specialised workshops in the activities of scraps recycling, irradiated fuel reprocessing, even fuel fabrication. Other steps of the cycle meet or will meet difficulties, in particular supplying of fissile raw material LEU or HEU because this material was mostly produced in enrichment units existing mainly for military reason. Rarefaction of fissile material lead to use more and more enriched uraniums said 'of technical quality', that is to say which come from mixing of varied qualities of enriched material, containing products resulting from reprocessing. Actually, problems of end of fuel cycle are increased, either consisting of intermediary storage on the site of reactor or on specialised sites, or consisting of reprocessing. This brief summary shows most difficulties which are met today by a major part of industrials of the fuel cycle in the exercise of their activities

Superelastic load cycling of Gum Metal

International Nuclear Information System (INIS)

Vorontsov, V.A.; Jones, N.G.; Rahman, K.M.; Dye, D.

2015-01-01

The superelastic beta titanium alloy, Gum Metal, has been found to accumulate plastic strain during tensile load cycling in the superelastic regime. This is evident from the positive drift of the macroscopic stress vs. strain hysteresis curve parallel to the strain axis and the change in its geometry subsequent to every load–unload cycle. In addition, there is a progressive reduction in the hysteresis loop width and in the stress at which the superelastic transition occurs. In situ synchrotron X-ray diffraction has shown that the lattice strain exhibited the same behaviour as that observed in macroscopic measurements and identified further evidence of plastic strain accumulation. The mechanisms responsible for the observed behaviour have been evaluated using transmission electron microscopy, which revealed a range of different defects that formed during load cycling. The formation of these defects is consistent with the classical mathematical theory for the bcc to orthorhombic martensitic transformation. It is the accumulation of these defects over time that alters its superelastic behaviour

The plant homolog to the human sodium/dicarboxylic cotransporter is the vacuolar malate carrier

OpenAIRE

Emmerlich, Vera; Linka, Nicole; Reinhold, Thomas; Hurth, Marco A.; Traub, Michaela; Martinoia, Enrico; Neuhaus, H. Ekkehard

2003-01-01

Malate plays a central role in plant metabolism. It is an intermediate in the Krebs and glyoxylate cycles, it is the store for CO2 in C4 and crassulacean acid metabolism plants, it protects plants from aluminum toxicity, it is essential for maintaining the osmotic pressure and charge balance, and it is therefore involved in regulation of stomatal aperture. To fulfil many of these roles, malate has to be accumulated within the large central vacuole. Many unsuccessful efforts have been made in ...

Cell cycle control by a minimal Cdk network.

Directory of Open Access Journals (Sweden)

Claude Gérard

2015-02-01

Full Text Available In present-day eukaryotes, the cell division cycle is controlled by a complex network of interacting proteins, including members of the cyclin and cyclin-dependent protein kinase (Cdk families, and the Anaphase Promoting Complex (APC. Successful progression through the cell cycle depends on precise, temporally ordered regulation of the functions of these proteins. In light of this complexity, it is surprising that in fission yeast, a minimal Cdk network consisting of a single cyclin-Cdk fusion protein can control DNA synthesis and mitosis in a manner that is indistinguishable from wild type. To improve our understanding of the cell cycle regulatory network, we built and analysed a mathematical model of the molecular interactions controlling the G1/S and G2/M transitions in these minimal cells. The model accounts for all observed properties of yeast strains operating with the fusion protein. Importantly, coupling the model's predictions with experimental analysis of alternative minimal cells, we uncover an explanation for the unexpected fact that elimination of inhibitory phosphorylation of Cdk is benign in these strains while it strongly affects normal cells. Furthermore, in the strain without inhibitory phosphorylation of the fusion protein, the distribution of cell size at division is unusually broad, an observation that is accounted for by stochastic simulations of the model. Our approach provides novel insights into the organization and quantitative regulation of wild type cell cycle progression. In particular, it leads us to propose a new mechanistic model for the phenomenon of mitotic catastrophe, relying on a combination of unregulated, multi-cyclin-dependent Cdk activities.

Pokemon enhances proliferation, cell cycle progression and anti-apoptosis activity of colorectal cancer independently of p14ARF-MDM2-p53 pathway.

Science.gov (United States)

Zhao, Yi; Yao, Yun-hong; Li, Li; An, Wei-fang; Chen, Hong-zen; Sun, Li-ping; Kang, Hai-xian; Wang, Sen; Hu, Xin-rong

2014-12-01

Pokemon has been showed to directly suppress p14(ARF) expression and also to overexpress in multiple cancers. However, p14(ARF)-MDM2-p53 pathway is usually aberrant in colorectal cancer (CRC). The aim is to confirm whether Pokemon plays a role in CRC and explore whether Pokemon works through p14(ARF)-MDM2-p53 pathway in CRC. Immunohistochemistry for Pokemon, p14(ARF) and Mtp53 protein was applied to 45 colorectal epitheliums (CREs), 42 colorectal adenomas (CRAs) and 66 CRCs. Pokemon was knocked down with RNAi technique in CRC cell line Lovo to detect mRNA expression of p14(ARF) with qRT-PCR, cell proliferation with CCK8 assay, and cell cycle and apoptosis with flowcytometry analysis. The protein expression rates were significantly higher in CRC (75.8%) than in CRE (22.2 %) or CRA (38.1%) for Pokemon and higher in CRC (53.0%) than in CRE (0) or CRA (4.8%) for Mtp53, but not significantly different in CRC (86.4 %) versus CRE (93.3%) or CRA (90.5 %) for p14(ARF). Higher expression rate of Pokemon was associated with lymph node metastasis and higher Duke's stage. After knockdown of Pokemon in Lovo cells, the mRNA level of p14(ARF) was not significantly changed, the cell proliferation ability was decreased by 20.6%, cell cycle was arrested by 55.7% in G0/G1 phase, and apoptosis rate was increased by 19.0%. Pokemon enhanced the oncogenesis of CRC by promoting proliferation, cell cycle progression and anti-apoptosis activity of CRC cells independently of p14(ARF)-MDM2-p53 pathway. This finding provided a novel idea for understanding and further studying the molecular mechanism of Pokemon on carcinogenesis of CRC.

Molecular machinery of signal transduction and cell cycle regulation in Plasmodium.

Science.gov (United States)

Koyama, Fernanda C; Chakrabarti, Debopam; Garcia, Célia R S

2009-05-01

The regulation of the Plasmodium cell cycle is not understood. Although the Plasmodium falciparum genome is completely sequenced, about 60% of the predicted proteins share little or no sequence similarity with other eukaryotes. This feature impairs the identification of important proteins participating in the regulation of the cell cycle. There are several open questions that concern cell cycle progression in malaria parasites, including the mechanism by which multiple nuclear divisions is controlled and how the cell cycle is managed in all phases of their complex life cycle. Cell cycle synchrony of the parasite population within the host, as well as the circadian rhythm of proliferation, are striking features of some Plasmodium species, the molecular basis of which remains to be elucidated. In this review we discuss the role of indole-related molecules as signals that modulate the cell cycle in Plasmodium and other eukaryotes, and we also consider the possible role of kinases in the signal transduction and in the responses it triggers.

Systematic analysis of cell cycle effects of common drugs leads to the discovery of a suppressive interaction between gemfibrozil and fluoxetine.

Science.gov (United States)

Hoose, Scott A; Duran, Camille; Malik, Indranil; Eslamfam, Shabnam; Shasserre, Samantha C; Downing, S Sabina; Hoover, Evelyn M; Dowd, Katherine E; Smith, Roger; Polymenis, Michael

2012-01-01

Screening chemical libraries to identify compounds that affect overall cell proliferation is common. However, in most cases, it is not known whether the compounds tested alter the timing of particular cell cycle transitions. Here, we evaluated an FDA-approved drug library to identify pharmaceuticals that alter cell cycle progression in yeast, using DNA content measurements by flow cytometry. This approach revealed strong cell cycle effects of several commonly used pharmaceuticals. We show that the antilipemic gemfibrozil delays initiation of DNA replication, while cells treated with the antidepressant fluoxetine severely delay progression through mitosis. Based on their effects on cell cycle progression, we also examined cell proliferation in the presence of both compounds. We discovered a strong suppressive interaction between gemfibrozil and fluoxetine. Combinations of interest among diverse pharmaceuticals are difficult to identify, due to the daunting number of possible combinations that must be evaluated. The novel interaction between gemfibrozil and fluoxetine suggests that identifying and combining drugs that show cell cycle effects might streamline identification of drug combinations with a pronounced impact on cell proliferation.

Systematic analysis of cell cycle effects of common drugs leads to the discovery of a suppressive interaction between gemfibrozil and fluoxetine.

Directory of Open Access Journals (Sweden)

Scott A Hoose

Full Text Available Screening chemical libraries to identify compounds that affect overall cell proliferation is common. However, in most cases, it is not known whether the compounds tested alter the timing of particular cell cycle transitions. Here, we evaluated an FDA-approved drug library to identify pharmaceuticals that alter cell cycle progression in yeast, using DNA content measurements by flow cytometry. This approach revealed strong cell cycle effects of several commonly used pharmaceuticals. We show that the antilipemic gemfibrozil delays initiation of DNA replication, while cells treated with the antidepressant fluoxetine severely delay progression through mitosis. Based on their effects on cell cycle progression, we also examined cell proliferation in the presence of both compounds. We discovered a strong suppressive interaction between gemfibrozil and fluoxetine. Combinations of interest among diverse pharmaceuticals are difficult to identify, due to the daunting number of possible combinations that must be evaluated. The novel interaction between gemfibrozil and fluoxetine suggests that identifying and combining drugs that show cell cycle effects might streamline identification of drug combinations with a pronounced impact on cell proliferation.

Comparison of low-cycle fatigue data of 2 1/4 % CrMo steels

International Nuclear Information System (INIS)

Sanderson, S.J.; Petrequin, P.; Nieuwland, H.C.D.; Breuer, H.J.

1983-01-01

Data files have been produced on international strain-controlled fatigue information available for 2 1/4 %CrMo steels. The available data have been considered generally in terms of total strain range vs. cycles to failure (Nsub(f)), tensile stress at Nsub(f)/2 vs. cycles to failure and time to failure vs. cycles to failure. Where possible the continuous cycling data been statistically analysed in terms of the elastic and plastic strain components and cycles to failure to yield best-fit equations over defined temperature (T) regime viz: T 0 C, 427 0 C 0 C and 550 0 C 0 C. Increasing test temperatures result in a progressive decrease in continuous cycling fatigue endurance and sustainable stress range

Rankine cycle generators using geothermal fluids. Final progress report

Energy Technology Data Exchange (ETDEWEB)

1981-01-01

The Rankine Cycle generator was delivered and installed at Gila Hot Springs. Trial runs were made at that time, using Freon 12 as the expansion fluid. These tests showed that the boiler capacity was inadequate. It could not extract enough heat to generate sufficient volumes of Freon gas at the heat and pressure necessary to operate the system at an acceptable level. Increasing and decreasing the flow of hot water had a direct influence on efficiency, but it was not a linear relationship. Added amounts of hot water increased the power very little, but raised the water temperature at the discharge point. This implied that the heat exchange capacity of the boiler was saturated. The reverse was found in the condenser system. There was little increase in pressure of the condenser when we switched from static to run mode. Efficiency was maintained even when the cold water flow was reduced as much as 40%. The tests using Freon 12 resulted in the conclusion that the boiler volume needs to be increased and/or the configuration changed to radically increase its efficiency.

Impact of cycling cells and cell cycle regulation on Hydra regeneration.

Science.gov (United States)

Buzgariu, Wanda; Wenger, Yvan; Tcaciuc, Nina; Catunda-Lemos, Ana-Paula; Galliot, Brigitte

2018-01-15

Hydra tissues are made from three distinct populations of stem cells that continuously cycle and pause in G2 instead of G1. To characterize the role of cell proliferation after mid-gastric bisection, we have (i) used flow cytometry and classical markers to monitor cell cycle modulations, (ii) quantified the transcriptomic regulations of 202 genes associated with cell proliferation during head and foot regeneration, and (iii) compared the impact of anti-proliferative treatments on regeneration efficiency. We confirm two previously reported events: an early mitotic wave in head-regenerating tips, when few cell cycle genes are up-regulated, and an early-late wave of proliferation on the second day, preceded by the up-regulation of 17 cell cycle genes. These regulations appear more intense after mid-gastric bisection than after decapitation, suggesting a position-dependent regulation of cell proliferation during head regeneration. Hydroxyurea, which blocks S-phase progression, delays head regeneration when applied before but not after bisection. This result is consistent with the fact that the Hydra central region is enriched in G2-paused adult stem cells, poised to divide upon injury, thus forming a necessary constitutive pro-blastema. However a prolonged exposure to hydroxyurea does not block regeneration as cells can differentiate apical structures without traversing S-phase, and also escape in few days the hydroxyurea-induced S-phase blockade. Thus Hydra head regeneration, which is a fast event, is highly plastic, relying on large stocks of adult stem cells paused in G2 at amputation time, which immediately divide to proliferate and/or differentiate apical structures even when S-phase is blocked. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Fluorine uptake into human enamel around a fluoride-containing dental material during cariogenic pH cycling

International Nuclear Information System (INIS)

Komatsu, H.; Yamamoto, H.; Nomachi, M.; Yasuda, K.; Matsuda, Y.; Murata, Y.; Kijimura, T.; Sano, H.; Sakai, T.; Kamiya, T.

2007-01-01

Using PIGE (TIARA, JAPAN) technique, we measured fluorine (F) uptake into the tooth enamel around a fluoride-containing material during caries progression using pH cycling. Class I cavities in the buccal surfaces of 6 extracted human teeth were drilled and filled with fluoride-containing material; a glass ionomer cement (Fuji IX(GC)). Three 300 μm sections through the material were obtained from each tooth. Two of these specimens were utilized to measure the F distribution in enamel adjacent to the material. A 1.7 MeV proton beam accelerated by the TIARA single-ended accelerator was delivered to a micro-beam apparatus. The beam spot size was about 1 μm with a beam current of about 100 pA. A nuclear reaction, 19 F(p, αγ) 16 0, was used to measure the F concentration and the gamma-rays from this reaction were detected with a 4' NaI detector. X-rays induced by proton were detected with a Si(Li) detector to measure calcium concentration and the beam intensity was monitored with the X-ray yield from a copper foil for quantitative analysis. After measurement of F uptake, all specimens were polished to a thickness of 120 μm. In order to simulate daily acid challenges occurring in the oral cavity, the pH cycling (pH6.8-pH4.5) was carried out for 1, 3 and 5 weeks, separately. The duration that the solution remained below pH 5.5 was 37 min per cycle. The cycles were repeated 6 times per day with 2 h interval between cycles, and the specimens were kept in remineralizing solution for the rest of pH cycle. After pH cycling, F and calcium distribution of each specimen was evaluated using PIGE technique. The F distribution of the specimens before pH cycling clearly showed the F uptake from fluoride-containing material into enamel adjacent to the material. After pH cycling, the caries progression in all specimens was observed by the image of transverse microradiography (TMR). The depth of caries and mineral loss progressed with increasing the duration of pH cycling, although

Fluorine uptake into human enamel around a fluoride-containing dental material during cariogenic pH cycling

Energy Technology Data Exchange (ETDEWEB)

Komatsu, H. [Graduate School of Dental Medicine, Hokkaido University, Kita-13, Nishi-7, Kita-ku, Sapporo 060-8586 (Japan)]. E-mail: kom@den.hokudai.ac.jp; Yamamoto, H. [Graduate School of Dentistry, Osaka University, 1-8 Yamada-Oka, Suita 565-0871 (Japan); Nomachi, M. [Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka 560-0043 (Japan); Yasuda, K. [Wakasa wan Energy Research Center, 64-52-1 Hase, Tsuruga 914-0192 (Japan); Matsuda, Y. [Graduate School of Dental Medicine, Hokkaido University, Kita-13, Nishi-7, Kita-ku, Sapporo 060-8586 (Japan); Murata, Y. [Graduate School of Dental Medicine, Hokkaido University, Kita-13, Nishi-7, Kita-ku, Sapporo 060-8586 (Japan); Kijimura, T. [Graduate School of Dental Medicine, Hokkaido University, Kita-13, Nishi-7, Kita-ku, Sapporo 060-8586 (Japan); Sano, H. [Graduate School of Dental Medicine, Hokkaido University, Kita-13, Nishi-7, Kita-ku, Sapporo 060-8586 (Japan); Sakai, T. [Takasaki Advanced Radiation Research Institute, JAEA, 1233 Watanuki-machi, Takasaki 370-1292 (Japan); Kamiya, T. [Takasaki Advanced Radiation Research Institute, JAEA, 1233 Watanuki-machi, Takasaki 370-1292 (Japan)

2007-07-15

Using PIGE (TIARA, JAPAN) technique, we measured fluorine (F) uptake into the tooth enamel around a fluoride-containing material during caries progression using pH cycling. Class I cavities in the buccal surfaces of 6 extracted human teeth were drilled and filled with fluoride-containing material; a glass ionomer cement (Fuji IX(GC)). Three 300 {mu}m sections through the material were obtained from each tooth. Two of these specimens were utilized to measure the F distribution in enamel adjacent to the material. A 1.7 MeV proton beam accelerated by the TIARA single-ended accelerator was delivered to a micro-beam apparatus. The beam spot size was about 1 {mu}m with a beam current of about 100 pA. A nuclear reaction, {sup 19}F(p, {alpha}{gamma}){sup 16}0, was used to measure the F concentration and the gamma-rays from this reaction were detected with a 4' NaI detector. X-rays induced by proton were detected with a Si(Li) detector to measure calcium concentration and the beam intensity was monitored with the X-ray yield from a copper foil for quantitative analysis. After measurement of F uptake, all specimens were polished to a thickness of 120 {mu}m. In order to simulate daily acid challenges occurring in the oral cavity, the pH cycling (pH6.8-pH4.5) was carried out for 1, 3 and 5 weeks, separately. The duration that the solution remained below pH 5.5 was 37 min per cycle. The cycles were repeated 6 times per day with 2 h interval between cycles, and the specimens were kept in remineralizing solution for the rest of pH cycle. After pH cycling, F and calcium distribution of each specimen was evaluated using PIGE technique. The F distribution of the specimens before pH cycling clearly showed the F uptake from fluoride-containing material into enamel adjacent to the material. After pH cycling, the caries progression in all specimens was observed by the image of transverse microradiography (TMR). The depth of caries and mineral loss progressed with increasing the

Thorium fuel cycle development activities in India (a decade of progress: 1981-1990)

International Nuclear Information System (INIS)

Basu, T.K.; Srinivasan, M.

1990-01-01

The report comprises of 72 papers on various aspects of thorium fuel cycle. These papers report the research work carried out at the Bhabha Atomic Research Centre, Bombay and other units of the Department of Atomic Energy during the decade 1981-1990. figs., tabs

Cycling Towards Progress: Ribociclib, CDK 4/6 inhibitor for Breast Cancer.

Science.gov (United States)

Spring, Laura; Bardia, Aditya

2018-04-23

Ribociclib is an orally active, highly selective inhibitor of cyclin-dependent kinase (CDK) 4 and 6. It is the second CDK 4/6 inhibitor approved for hormone receptor-positive breast cancer. The addition of ribociclib to an aromatase inhibitor has resulted in marked improvements in progression-free survival for patients with metastatic breast cancer. Copyright ©2018, American Association for Cancer Research.

Dynamic protein S-palmitoylation mediates parasite life cycle progression and diverse mechanisms of virulence.

Science.gov (United States)

Brown, Robert W B; Sharma, Aabha I; Engman, David M

2017-04-01

Eukaryotic parasites possess complex life cycles and utilize an assortment of molecular mechanisms to overcome physical barriers, suppress and/or bypass the host immune response, including invading host cells where they can replicate in a protected intracellular niche. Protein S-palmitoylation is a dynamic post-translational modification in which the fatty acid palmitate is covalently linked to cysteine residues on proteins by the enzyme palmitoyl acyltransferase (PAT) and can be removed by lysosomal palmitoyl-protein thioesterase (PPT) or cytosolic acyl-protein thioesterase (APT). In addition to anchoring proteins to intracellular membranes, functions of dynamic palmitoylation include - targeting proteins to specific intracellular compartments via trafficking pathways, regulating the cycling of proteins between membranes, modulating protein function and regulating protein stability. Recent studies in the eukaryotic parasites - Plasmodium falciparum, Toxoplasma gondii, Trypanosoma brucei, Cryptococcus neoformans and Giardia lamblia - have identified large families of PATs and palmitoylated proteins. Many palmitoylated proteins are important for diverse aspects of pathogenesis, including differentiation into infective life cycle stages, biogenesis and tethering of secretory organelles, assembling the machinery powering motility and targeting virulence factors to the plasma membrane. This review aims to summarize our current knowledge of palmitoylation in eukaryotic parasites, highlighting five exemplary mechanisms of parasite virulence dependent on palmitoylation.

Reprocessing on the whole fuel cycle operations

International Nuclear Information System (INIS)

Megy, J.

1983-11-01

Spent fuel reprocessing, in France, is become an industrial reality which takes an importance place in several fields: place surely essential in the fuel cycle from the energetic material economy and waste management point of view; place priority in the CEA (Commissariat a l'Energie Atomique) research and development programs; place in the industry where it is an important activity sector with the realizations in progress [fr

5-AED Enhances Survival of Irradiated Mice in a G-CSF-Dependent Manner, Stimulates Innate Immune Cell Function, Reduces Radiation-Induced DNA Damage and Induces Genes that Modulate Cell Cycle Progression and Apoptosis

Science.gov (United States)

2012-07-22

modulate cell cycle progression and apoptosis. INTRODUCTION Because of the increasing threat posed by nuclear weapons [1], there is a pressing need for both...Detection System ( Bio -Rad Laboratories, Hercules CA) on 96-well microtiter plates with optical caps. Reactions were performed in a total volume of 50 µL... antigen -induced arthritis by dehydroepiandrosterone (DHEA). Inflamm Res 2004;53:189–98. 56. Auci D, Nicoletti F, Mangano K et al. Anti-inflammatory and

Fuel-cycle programs. Quarterly progress report, January-March 1981

International Nuclear Information System (INIS)

Steindler, M.J.; Vogler, S.; Vandegrift, G.F.

1982-03-01

A program continues for the development of an interim waste form that can be transported from facilities where waste is generated to terminal waste processing. Measurements of rates of leaching from simulated nuclear waste forms ar continuing. The data suggest that leaching from SRL glasses is inhibited by the formation of a Si/Ca/Fe/Al-rich surface layer. Impact tests of solid alternative waste forms (glass and ceramic) are being performed to assess source terms of airborne release (from particle size distributions) and to assess the increases in source terms of leach rates (from increases in surface area). Logging techniques are being developed to measure the relative amount of residual oil in a depleted oil reservoir. A simple technique for the elution of pore fluid (groundwater) from igneous rocks is described, using a special coreholder, as is the elution of brine (in the same apparatus) from a core of Precambrian granite. Testing and development of equipment for the destructive analysis of full-length irradiated fuel rods from the LWBR is in progress

MAT-FLX: a simplified code for computing material balances in fuel cycle

International Nuclear Information System (INIS)

Pierantoni, F.; Piacentini, F.

1983-01-01

This work illustrates a calculation code designed to provide a materials balance for the electro nuclear fuel cycle. The calculation method is simplified but relatively precise and employs a progressive tabulated data approach

Geodynamics Project. US progress report, 1975

Energy Technology Data Exchange (ETDEWEB)

1976-01-01

The recommendations of the US Geodynamics Committee relative to program activities are presented. US Program progress is reviewed in the following areas: fine structure of the crust and upper mantle; continuous seismic reflection profiling of the deep basement: Hardeman County, Texas; Mid-Atlantic Ridge - evolution of oceanic lithosphere; internal processes and properties; crystal growing; chemical differentiation of magmas; geodynamic modelling; magnetic problems; plate boundaries; plate interiors; geodynamic syntheses; and eustatic cycles of sea level changes. (MHR)

Effects of recombinant plasmid pEgr-p53 transfected stably in combination with X-irradiation on cell cycle progression and proliferation in human SKOV-3 tumor cells in vitro

International Nuclear Information System (INIS)

Dong Lihua; Liu Feng; Li Yanbo; Fu Shibo; Gong Shouliang

2008-01-01

Objective: To investigate the effect of recombinant plasmid pEgr-hp53 transfected stably in combination with X-ray irradiation on the cell cycle progression and the proliferation in human SKOV-3 tumor cells. Methods: pEgr-hp53 and pcDNA3.1 packaged with liposome were stably transfected into SKOV-3 cells in vitro. SKOV-3-hp53 and SKOV-3-vect were irradiated with 0, 0.5, 2.0 and 5.0 Gy X-rays, respectively, i.e. 8 experimental groups. The SKOV-3 cell proliferation and the cell cycle progression were measured with flow cytometry and cell growth curve, respectively. Results: Compared with 0 Gy group, the cell counts in SKOV-3- hp53 plus different doses of irradiation groups 2 d after irradiation decreased significantly (P 0 /G 1 cells increased significantly (P 2 /M cells decreased in varying degrees. The cell counts in SKOV-3-hp53 plus irradiation group were significantly lower than those in corresponding SKOV-3-vect plus irradiation group, the cell counts 4-8 d after irradiation with 0.5 Gy, 2 d after 2.0 Gy irradiation and 6 d after 5.0 Gy irradiation decreased significantly (P 0 /G 1 cells increased significantly (P 2 /M cells decreased significantly (P 1 arrest in SKOV-3 cells and inhibits the cell proliferation. Ionizing radiation can activate early growth response-1 (Egr-1) gene promoter and increase the expression of p53 gene, and enhance the inhibition of tumor cell growth. (authors)

Visualizing the Cardiac Cycle: A Useful Tool to Promote Student Understanding

Directory of Open Access Journals (Sweden)

Ivan Shun Ho

2011-03-01

Full Text Available The cardiac cycle is an important concept presented in human anatomy and physiology courses. At Kingsborough Community College, all Allied Health majors taking Anatomy & Physiology must understand the cardiac cycle to grasp more advanced concepts. Contemporary textbooks illustrate the cardiac cycle’s concurrent events via linear models with overlapping line segments as physiological readouts. This presentation is appropriate for reference but, in the interactive classroom the promotion of understanding through clear, concise visual cues is essential. Muzio and Pilchman created a diagram to summarize events of the cardiac cycle. After discussions with one of the authors, I modified the diagram to aid visualization of the cycle and emphasize it as a repetitive, continuous process. A flow diagram presenting the portions of the cycle individually and progressively was also constructed. Three labeled phases are made from the diagram, based on grouped events occurring at different points. The simple, compartmentalized, cyclical diagram presented here promotes understanding of the cardiac cycle visually.

The Plasmodium serine-type SERA proteases display distinct expression patterns and non-essential in vivo roles during life cycle progression of the malaria parasite.

Science.gov (United States)

Putrianti, Elyzana D; Schmidt-Christensen, Anja; Arnold, Iris; Heussler, Volker T; Matuschewski, Kai; Silvie, Olivier

2010-06-01

Parasite proteases play key roles in several fundamental steps of the Plasmodium life cycle, including haemoglobin degradation, host cell invasion and parasite egress. Plasmodium exit from infected host cells appears to be mediated by a class of papain-like cysteine proteases called 'serine repeat antigens' (SERAs). A SERA subfamily, represented by Plasmodium falciparum SERA5, contains an atypical active site serine residue instead of a catalytic cysteine. Members of this SERAser subfamily are abundantly expressed in asexual blood stages, rendering them attractive drug and vaccine targets. In this study, we show by antibody localization and in vivo fluorescent tagging with the red fluorescent protein mCherry that the two P. berghei serine-type family members, PbSERA1 and PbSERA2, display differential expression towards the final stages of merozoite formation. Via targeted gene replacement, we generated single and double gene knockouts of the P. berghei SERAser genes. These loss-of-function lines progressed normally through the parasite life cycle, suggesting a specialized, non-vital role for serine-type SERAs in vivo. Parasites lacking PbSERAser showed increased expression of the cysteine-type PbSERA3. Compensatory mechanisms between distinct SERA subfamilies may thus explain the absence of phenotypical defect in SERAser disruptants, and challenge the suitability to develop potent antimalarial drugs based on specific inhibitors of Plasmodium serine-type SERAs.

Inventories in the Australian business cycle

OpenAIRE

Chindamo, Phillip

2010-01-01

This Economics Research Note examines inventories in the business cycle for Australia covering the period since the mid 1980s. The Australian Bureau of Statistics (ABS) defines inventories as all materials etc., work in progress and finished goods owned by a business, whether held at locations of the business or elsewhere. These items are usually held by businesses in anticipation of a product’s sale. Inventory investment is counted as an additional contribution to gross domestic product (...

Around the laboratories: Dubna: Physics results and progress on bubble chamber techniques; Stanford (SLAC): Operation of a very rapid cycling bubble chamber; Daresbury: Photographs of visitors to the Laboratory; Argonne: Charge exchange injection tests into the ZGS in preparation for a proposed Booster

CERN Multimedia

1969-01-01

Around the laboratories: Dubna: Physics results and progress on bubble chamber techniques; Stanford (SLAC): Operation of a very rapid cycling bubble chamber; Daresbury: Photographs of visitors to the Laboratory; Argonne: Charge exchange injection tests into the ZGS in preparation for a proposed Booster

Immunohistochemical analyses of cell cycle progression and gene expression of biliary epithelial cells during liver regeneration after partial hepatectomy of the mouse.

Science.gov (United States)

Fukuda, Tatsuya; Fukuchi, Tomokazu; Yagi, Shinomi; Shiojiri, Nobuyoshi

2016-05-20

The liver has a remarkable regeneration capacity, and, after surgical removal of its mass, the remaining tissue undergoes rapid regeneration through compensatory growth of its constituent cells. Although hepatocytes synchronously proliferate under the control of various signaling molecules from neighboring cells, there have been few detailed analyses on how biliary cells regenerate for their cell population after liver resection. The present study was undertaken to clarify how biliary cells regenerate after partial hepatectomy of mice through extensive analyses of their cell cycle progression and gene expression using immunohistochemical and RT-PCR techniques. When expression of PCNA, Ki67 antigen, topoisomerase IIα and phosphorylated histone H3, which are cell cycle markers, was immunohistochemically examined during liver regeneration, hepatocytes had a peak of the S phase and M phase at 48-72 h after resection. By contrast, biliary epithelial cells had much lower proliferative activity than that of hepatocytes, and their peak of the S phase was delayed. Mitotic figures were rarely detectable in biliary cells. RT-PCR analyses of gene expression of biliary markers such as Spp1 (osteopontin), Epcam and Hnf1b demonstrated that they were upregulated during liver regeneration. Periportal hepatocytes expressed some of biliary markers, including Spp1 mRNA and protein. Some periportal hepatocytes had downregulated expression of HNF4α and HNF1α. Gene expression of Notch signaling molecules responsible for cell fate decision of hepatoblasts to biliary cells during development was upregulated during liver regeneration. Notch signaling may be involved in biliary regeneration.

Commercial Alpha Waste Program. Quarterly progress report, January--March, 1975

International Nuclear Information System (INIS)

Cooley, C.R.

1975-10-01

This is the fourth quarterly progress report on the Commercial Alpha Waste Program being conducted at the Hanford Engineering Development Laboratory (HEDL) for the Division of Nuclear Fuel Cycle and Production, U. S. Energy Research and Development Administration. Data on waste composition for fuel reprocessing operations are discussed as well as information on radwaste generation at nuclear power reactors. Progress to date on development of the acid digestion process for treating combustible waste is discussed including initial studies using a critically safe tray digester. Data on alpha waste generation and product storage are also presented

Cell growth and division cycle

International Nuclear Information System (INIS)

Darzynkiewicz, Z.

1986-01-01

The concept of the cell cycle in its present form was introduced more than three decades ago. Studying incorporation of DNA precursors by autoradiography, these authors observed that DNA synthesis in individual cells was discontinuous and occupied a discrete portion of the cell life (S phase). Mitotic division was seen to occur after a certain period of time following DNA replication. A distinct time interval between mitosis and DNA replication was also apparent. Thus, the cell cycle was subdivided into four consecutive phases, G/sub 1/, S, G/sub 2/, and M. The G/sub 1/ and G/sub 2/ phases represented the ''gaps'' between mitosis and the start of DNA replication, and between the end of DNA replication and the onset of mitosis, respectively. The cell cycle was defined as the interval between the midpoint of mitosis and the midpoint of the subsequent mitosis of the daughter cell(s). The authors' present knowledge on the cell cycle benefited mostly from the development of four different techniques: autoradiography, time-lapse cinematography, cell synchronization and flow cytometry. Of these, autoradiography has been the most extensively used, especially during the past two decades. By providing a means to analyse incorporation of precursors of DNA, RNA or proteins by individual cells and, in combination with various techniques of cell synchronization, autoradiography yielded most of the data fundamental to the current understanding of the cell cycle-related phenomena. Kinetics of cell progression through the cell cycle could be analysed in great detail after development of such sophisticated autoradiographic approaches as measurements of the fraction of labeled mitoses (''FLM curves'') or multiple sequential cell labelling with /sup 3/H- and /sup 14/C-TdR

Integral Fast Reactor Program annual progress report, FY 1994

International Nuclear Information System (INIS)

Chang, Y.I.; Walters, L.C.; Laidler, J.J.; Pedersen, D.R.; Wade, D.C.; Lineberry, J.J.

1994-12-01

This report summarizes highlights of the technical progress made in the Integral Fast Reactor (IFR) Program in FY 1994. Technical accomplishments are presented in the following areas of the IFR technology development activities: metal fuel performance; pyroprocess development; safety experiments and analyses; core design development; fuel cycle demonstration; and LMR technology R ampersand D

Progress report 2005-2007 - Energy and Nuclear Research Institute - IPEN

International Nuclear Information System (INIS)

2008-01-01

This progress report presents the results of the R and D center of IPEN in accordance with the main programs: Radiopharmacy; Application of Ionizing Radiations; Nuclear Science and Technology; Nuclear Reactors and Fuel Cycle; Environmental Science and Technology; Renewable Energies; Materials and Nanotechnology; Biotechnology; Lasers Technology and Education

Cell cycle delays in synchronized cell populations following irradiation with heavy ions

International Nuclear Information System (INIS)

Scholz, M.

1992-11-01

Mammalian cells subjected to irradiation with heavy ions were investigated for cell cycle delays. The ions used for this purpose included Ne ions in the LET range of 400 keV/μm just as well as uranium ions of 16225 keV/μm. The qualitative changes in cell cycle progression seen after irradiation with Ne ions (400 keV/μm) were similar to those observed in connection with X-rays. Following irradiation with extremely heavy ions (lead, uranium) the majority of cells were even at 45 hours still found to be in the S phase or G 2 M phase of the first cycle. The delay cross section 'σ-delay' was introduced as a quantity that would permit quantitative comparisons to be carried out between the changes in cell progression and other effects of radiation. In order to evaluate the influence of the number of hits on the radiation effect observed, the size of the cell nucleus was precisely determined with reference to the cycle phase and local cell density. A model to simulate those delay effects was designed in such a way that account is taken of this probability of hit and that the results can be extrapolated from the delay effects after X-irradiation. On the basis of the various probabilities of hit for cells at different cycle stages a model was developed to ascertain the intensified effect following fractionated irradiation with heavy ions. (orig./MG) [de

The p75NTR tumor suppressor induces cell cycle arrest facilitating caspase mediated apoptosis in prostate tumor cells

International Nuclear Information System (INIS)

Khwaja, Fatima; Tabassum, Arshia; Allen, Jeff; Djakiew, Daniel

2006-01-01

The p75 neurotrophin receptor (p75 NTR ) is a death receptor which belongs to the tumor necrosis factor receptor super-family of membrane proteins. This study shows that p75 NTR retarded cell cycle progression by induced accumulation of cells in G0/G1 and a reduction in the S phase of the cell cycle. The rescue of tumor cells from cell cycle progression by a death domain deleted (ΔDD) dominant-negative antagonist of p75 NTR showed that the death domain transduced anti-proliferative activity in a ligand-independent manner. Conversely, addition of NGF ligand rescued retardation of cell cycle progression with commensurate changes in components of the cyclin/cdk holoenzyme complex. In the absence of ligand, p75 NTR -dependent cell cycle arrest facilitated an increase in apoptotic nuclear fragmentation of the prostate cancer cells. Apoptosis of p75 NTR expressing cells occurred via the intrinsic mitochondrial pathway leading to a sequential caspase-9 and -7 cascade. Since the death domain deleted dominant-negative antagonist of p75 NTR rescued intrinsic caspase associated apoptosis in PC-3 cells, this shows p75 NTR was integral to ligand independent induction of apoptosis. Moreover, the ability of ligand to ameliorate the p75 NTR -dependent intrinsic apoptotic cascade indicates that NGF functioned as a survival factor for p75 NTR expressing prostate cancer cells

Life cycle analysis of advanced nuclear power generation technologies

International Nuclear Information System (INIS)

Uchiyama, Yoji; Yokoyama, Hayaichi

1996-01-01

In this research, as for light water reactors and fast breeder reactors, for the object of all the processes from the mining, transport and refining of fuel, electric power generation to the treatment and disposal of waste, the amount of energy input and the quantity of CO 2 emission over the life cycle were analyzed, and regarding the influence that the technical progress of nuclear power generation exerted to environment, the effect of improvement was elucidated. Attention has been paid to nuclear power generation as its CO 2 emission is least, and the effect of global warming is smallest. In order to reduce the quantity of radioactive waste generation in LWRs and the cost of fuel cycle, and to extend the operation cycle, the technical development for heightening fuel burnup is in progress. The process of investigation of the new technologies of nuclear power generation taken up in this research is described. The analysis of the energy balance of various power generation methods is discussed. In the case of pluthermal process, the improvement of energy balance ratio is dependent on uranium enrichment technology. Nuclear power generation requires much materials and energy for the construction, and emits CO 2 indirectly. The CO 2 unit emission based on the analysis of energy balance was determined for the new technologies of nuclear power generation, and the results are shown. (K.I.)

Emerging Trends in the Nuclear Fuel Cycle: Implications for Waste Management

International Nuclear Information System (INIS)

Spradley, L.; Camper, L.; Rehmann, M.

2009-01-01

There are emerging trends in the nuclear fuel cycle that have implications for waste management. This paper will discuss activities in both the front-end and back-end of the nuclear fuel cycle for the U.S. Nuclear Regulatory Commission (NRC)-regulated entities. Particular focus will be given to the front-end which includes uranium recovery facilities, conversion facilities, and enrichment facilities. The back-end activities include progress on the proposed high-level waste geologic repository at Yucca Mountain, NV and efforts to reprocess spent nuclear fuel or down-blend HEU. While there are potential environmental impacts due to construction and dismantling of fuel cycle facilities, this paper focuses on the operational waste stream that will need to be managed as a result of fuel-cycle facilities. (authors)

The DUPIC alternative for backend fuel cycle

International Nuclear Information System (INIS)

Lee, J.S.; Yang, M.S.; Park, H.S.; Boczar, P.; Sullivan, J.; Gadsby, R.D.

1997-01-01

The DUPIC fuel cycle was conceived as an alternative to the conventional fuel cycle backed options, with a view to multiple benefits expectable from burning spent PWR fuel again in CANDU reactors. It is based on the basic idea that the bulk of spent PWR fuel can be directly refabricated into a reusable fuel for CANDU of which high efficiency in neutron utilization would exhaustively burn the fissile remnants in the spent PWR fuel to a level below that of natural uranium. Such ''burn again'' strategy of the DUPIC fuel cycle implies that the spent PWR fuel will become CANDU fuel of higher burnup with relevant benefits such as spent PWR fuel disposition, saving of natural uranium fuel, etc. A salient feature of the DUPIC fuel cycle is neither the fissile content nor the bulk radioactivity is separated from the DUPIC mass flow which must be contained and shielded all along the cycle. This feature can be considered as a factor of proliferation resistance by deterrence against access to sensitive materials. It means also the requirement for remote systems technologies for DUPIC fuel operation. The conflicting aspects between better safeguardability and harder engineering problems of the radioactive fuel operation may be the important reason why the decades' old concept, since INFCE, of ''hot'' fuel cycle has not been pursued with much progress. In this context, the DUPIC fuel cycle could be a live example for development of proliferation resistant fuel cycle. As the DUPIC fuel cycle looks for synergism of fuel linkage from PWR to CANDU (or in broader sense LWR to HWR), Korea occupies a best position for DUPIC exercise with her unique strategy of reactor mix of both reactor types. But the DUPIC benefits can be extended to global bonus, expectable from successful development of the technology. (author)

Restrictions in cell cycle progression of adult vestibular supporting cells in response to ectopic cyclin D1 expression.

Directory of Open Access Journals (Sweden)

Heidi Loponen

Full Text Available Sensory hair cells and supporting cells of the mammalian inner ear are quiescent cells, which do not regenerate. In contrast, non-mammalian supporting cells have the ability to re-enter the cell cycle and produce replacement hair cells. Earlier studies have demonstrated cyclin D1 expression in the developing mouse supporting cells and its downregulation along maturation. In explant cultures of the mouse utricle, we have here focused on the cell cycle control mechanisms and proliferative potential of adult supporting cells. These cells were forced into the cell cycle through adenoviral-mediated cyclin D1 overexpression. Ectopic cyclin D1 triggered robust cell cycle re-entry of supporting cells, accompanied by changes in p27(Kip1 and p21(Cip1 expressions. Main part of cell cycle reactivated supporting cells were DNA damaged and arrested at the G2/M boundary. Only small numbers of mitotic supporting cells and rare cells with signs of two successive replications were found. Ectopic cyclin D1-triggered cell cycle reactivation did not lead to hyperplasia of the sensory epithelium. In addition, a part of ectopic cyclin D1 was sequestered in the cytoplasm, reflecting its ineffective nuclear import. Combined, our data reveal intrinsic barriers that limit proliferative capacity of utricular supporting cells.

Restrictions in cell cycle progression of adult vestibular supporting cells in response to ectopic cyclin D1 expression.

Science.gov (United States)

Loponen, Heidi; Ylikoski, Jukka; Albrecht, Jeffrey H; Pirvola, Ulla

2011-01-01

Sensory hair cells and supporting cells of the mammalian inner ear are quiescent cells, which do not regenerate. In contrast, non-mammalian supporting cells have the ability to re-enter the cell cycle and produce replacement hair cells. Earlier studies have demonstrated cyclin D1 expression in the developing mouse supporting cells and its downregulation along maturation. In explant cultures of the mouse utricle, we have here focused on the cell cycle control mechanisms and proliferative potential of adult supporting cells. These cells were forced into the cell cycle through adenoviral-mediated cyclin D1 overexpression. Ectopic cyclin D1 triggered robust cell cycle re-entry of supporting cells, accompanied by changes in p27(Kip1) and p21(Cip1) expressions. Main part of cell cycle reactivated supporting cells were DNA damaged and arrested at the G2/M boundary. Only small numbers of mitotic supporting cells and rare cells with signs of two successive replications were found. Ectopic cyclin D1-triggered cell cycle reactivation did not lead to hyperplasia of the sensory epithelium. In addition, a part of ectopic cyclin D1 was sequestered in the cytoplasm, reflecting its ineffective nuclear import. Combined, our data reveal intrinsic barriers that limit proliferative capacity of utricular supporting cells.

Comparative study of the antitumor effect of natural monoterpenes: relationship to cell cycle analysis

Directory of Open Access Journals (Sweden)

Abdeslam Jaafari

2012-06-01

Full Text Available Monoterpenes have been identified as responsible of important therapeutic effects of plant-extracts. In this work, we try to compare the cytotoxic effect of six monoterpenes (carvacrol, thymol, carveol, carvone, eugenol and isopulegol as well as their molecular mechanisms. The in vitro antitumor activity of the tested products, evaluated against five tumor cell lines, show that the carvacrol is the most cytotoxic monoterpene. The investigation of an eventual synergistic effect of the six natural monoterpenes with two anticancer drugs revealed that there is a significant synergy between them (p<5%. On the other hand, the effect of the tested products on cell cycle progression was examined by flow cytometry after DNA staining in order to investigate the molecular mechanism of their cytotoxic activity. The results revealed that carvacrol and carveol stopped the cell cycle progression in S phase; however, thymol and isopulegol stopped it in G0/G1 phase. Regarding carvone and eugenol, no effect on cell cycle was observed.

Integral Fast Reactor Program. Annual progress report, FY 1992

Energy Technology Data Exchange (ETDEWEB)

Chang, Y.I.; Walters, L.C.; Laidler, J.J.; Pedersen, D.R.; Wade, D.C.; Lineberry, M.J.

1993-06-01

This report summarizes highlights of the technical progress made in the Integral Fast Reactor (IFR) Program in FY 1992. Technical accomplishments are presented in the following areas of the IFR technology development activities: (1) metal fuel performance, (2) pyroprocess development, (3) safety experiments and analyses, (4) core design development, (5) fuel cycle demonstration, and (6) LMR technology R&D.

Toona Sinensis Extracts Induced Cell Cycle Arrest and Apoptosis in the Human Lung Large Cell Carcinoma

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Cheng-Yuan Wang

2010-02-01

Full Text Available Toona sinensis extracts have been shown to exhibit anti-cancer effects in human ovarian cancer cell lines, human promyelocytic leukemia cells and human lung adenocarcinoma. Its safety has also been confirmed in animal studies. However, its anti-cancer properties in human lung large cell carcinoma have not been studied. Here, we used a powder obtained by freeze-drying the super-natant of centrifuged crude extract from Toona sinensis leaves (TSL-1 to treat the human lung carcinoma cell line H661. Cell viability was evaluated by the 3-(4-,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide assay. Flow cytometry analysis revealed that TSL-1 blocked H661 cell cycle progression. Western blot analysis showed decreased expression of cell cycle proteins that promote cell cycle progression, including cyclin-dependent kinase 4 and cyclin D1, and increased the expression of proteins that inhibit cell cycle progression, including p27. Furthermore, flow cytometry analysis showed that TSL-1 induced H661 cell apoptosis. Western blot analysis showed that TSL-1 reduced the expression of the anti-apoptotic protein B-cell lymphoma 2, and degraded the DNA repair protein, poly(ADP-ribose polymerase. TSL-1 shows potential as a novel therapeutic agent or for use as an adjuvant for treating human lung large cell carcinoma.

Malate and fumarate extend lifespan in Caenorhabditis elegans.

Directory of Open Access Journals (Sweden)

Clare B Edwards

Full Text Available Malate, the tricarboxylic acid (TCA cycle metabolite, increased lifespan and thermotolerance in the nematode C. elegans. Malate can be synthesized from fumarate by the enzyme fumarase and further oxidized to oxaloacetate by malate dehydrogenase with the accompanying reduction of NAD. Addition of fumarate also extended lifespan, but succinate addition did not, although all three intermediates activated nuclear translocation of the cytoprotective DAF-16/FOXO transcription factor and protected from paraquat-induced oxidative stress. The glyoxylate shunt, an anabolic pathway linked to lifespan extension in C. elegans, reversibly converts isocitrate and acetyl-CoA to succinate, malate, and CoA. The increased longevity provided by malate addition did not occur in fumarase (fum-1, glyoxylate shunt (gei-7, succinate dehydrogenase flavoprotein (sdha-2, or soluble fumarate reductase F48E8.3 RNAi knockdown worms. Therefore, to increase lifespan, malate must be first converted to fumarate, then fumarate must be reduced to succinate by soluble fumarate reductase and the mitochondrial electron transport chain complex II. Reduction of fumarate to succinate is coupled with the oxidation of FADH2 to FAD. Lifespan extension induced by malate depended upon the longevity regulators DAF-16 and SIR-2.1. Malate supplementation did not extend the lifespan of long-lived eat-2 mutant worms, a model of dietary restriction. Malate and fumarate addition increased oxygen consumption, but decreased ATP levels and mitochondrial membrane potential suggesting a mild uncoupling of oxidative phosphorylation. Malate also increased NADPH, NAD, and the NAD/NADH ratio. Fumarate reduction, glyoxylate shunt activity, and mild mitochondrial uncoupling likely contribute to the lifespan extension induced by malate and fumarate by increasing the amount of oxidized NAD and FAD cofactors.

Crack growth through low-cycle fatigue loading of material ARMOX 500T

Directory of Open Access Journals (Sweden)

V. Pepel

2016-10-01

Full Text Available This paper presents microstructure analysis of the creation and growth of cracks in uniaxial load. Analyse were done for steel Armox 500T (armour sheet. Results show that cracks are present quit early in steel lifetime. First micro cracks occur before the 200th cycles, whereby crack growth is progressive during further loading. Also it can be seen that after a certain number of cycles there are more longer cracks then shorter ones.

Molecular biological mechanism II. Molecular mechanisms of cell cycle regulation

International Nuclear Information System (INIS)

Jung, T.

2000-01-01

The cell cycle in eukaryotes is regulated by central cell cycle controlling protein kinase complexes. These protein kinase complexes consist of a catalytic subunit from the cyclin-dependent protein kinase family (CDK), and a regulatory subunit from the cyclin family. Cyclins are characterised by their periodic cell cycle related synthesis and destruction. Each cell cycle phase is characterised by a specific set of CDKs and cyclins. The activity of CDK/cyclin complexes is mainly regulated on four levels. It is controlled by specific phosphorylation steps, the synthesis and destruction of cyclins, the binding of specific inhibitor proteins, and by active control of their intracellular localisation. At several critical points within the cell cycle, named checkpoints, the integrity of the cellular genome is monitored. If damage to the genome or an unfinished prior cell cycle phase is detected, the cell cycle progression is stopped. These cell cycle blocks are of great importance to secure survival of cells. Their primary importance is to prevent the manifestation and heritable passage of a mutated genome to daughter cells. Damage sensing, DNA repair, cell cycle control and apoptosis are closely linked cellular defence mechanisms to secure genome integrity. Disregulation in one of these defence mechanisms are potentially correlated with an increased cancer risk and therefore in at least some cases with an increased radiation sensitivity. (orig.) [de

The role of sustainability and life cycle thinking in U.S. biofuels policies

International Nuclear Information System (INIS)

Soratana, Kullapa; Harden, Cheyenne L.; Zaimes, George G.; Rasutis, Daina; Antaya, Claire L.; Khanna, Vikas; Landis, Amy E.

2014-01-01

A comprehensive review of the U.S. federal biofuel-related policies, from 1955 to 2012, was conducted to examine the progression of life cycle thinking within the policies. Over 1300 past and present federal and state biofuel laws and incentives were analyzed to identify the establishment of Life-cycle thinking (LCT) in the biofuel policies. The policies were searched for search terms representing the three themes: life cycle assessment, environmental impact and sustainability. LCT in policies was first seen in the Renewable Fuel Standard under the Energy Independence and Security Act of 2007, where life-cycle greenhouse gas emissions reduction of biofuels was required. Existing U.S. biofuel policies were also characterized to define types of policy as tax incentive, grants, mandate, etc. The results suggested that climate change or energy incentives, air quality or emissions, etc. should be more emphasized in fuel legislation for a continuous improvement of biofuels industry. Only 13% of both the federal and state policies reviewed in this study employed some aspect of LCT. Policies that incorporate LCT often only focused on greenhouse gas emissions; policies should include other environmental impacts to avoid any environmental tradeoffs and unintended consequences from biofuel production. - Highlights: • Identified the establishment of sustainability and life-cycle thinking in biofuel policy. • Presented the spatial distribution of state U.S. biofuels policies and production via GIS. • Analyzed past and present federal and state environmental policies progression toward biofuels. • Life-cycle thinking was only present in 13% of federal and state policies current as of 2013

The emerging role and targetability of the TCA cycle in cancer metabolism.

Science.gov (United States)

Anderson, Nicole M; Mucka, Patrick; Kern, Joseph G; Feng, Hui

2018-02-01

The tricarboxylic acid (TCA) cycle is a central route for oxidative phosphorylation in cells, and fulfills their bioenergetic, biosynthetic, and redox balance requirements. Despite early dogma that cancer cells bypass the TCA cycle and primarily utilize aerobic glycolysis, emerging evidence demonstrates that certain cancer cells, especially those with deregulated oncogene and tumor suppressor expression, rely heavily on the TCA cycle for energy production and macromolecule synthesis. As the field progresses, the importance of aberrant TCA cycle function in tumorigenesis and the potentials of applying small molecule inhibitors to perturb the enhanced cycle function for cancer treatment start to evolve. In this review, we summarize current knowledge about the fuels feeding the cycle, effects of oncogenes and tumor suppressors on fuel and cycle usage, common genetic alterations and deregulation of cycle enzymes, and potential therapeutic opportunities for targeting the TCA cycle in cancer cells. With the application of advanced technology and in vivo model organism studies, it is our hope that studies of this previously overlooked biochemical hub will provide fresh insights into cancer metabolism and tumorigenesis, subsequently revealing vulnerabilities for therapeutic interventions in various cancer types.

The emerging role and targetability of the TCA cycle in cancer metabolism

Directory of Open Access Journals (Sweden)

Nicole M. Anderson

2017-07-01

Full Text Available ABSTRACT The tricarboxylic acid (TCA cycle is a central route for oxidative phosphorylation in cells, and fulfills their bioenergetic, biosynthetic, and redox balance requirements. Despite early dogma that cancer cells bypass the TCA cycle and primarily utilize aerobic glycolysis, emerging evidence demonstrates that certain cancer cells, especially those with deregulated oncogene and tumor suppressor expression, rely heavily on the TCA cycle for energy production and macromolecule synthesis. As the field progresses, the importance of aberrant TCA cycle function in tumorigenesis and the potentials of applying small molecule inhibitors to perturb the enhanced cycle function for cancer treatment start to evolve. In this review, we summarize current knowledge about the fuels feeding the cycle, effects of oncogenes and tumor suppressors on fuel and cycle usage, common genetic alterations and deregulation of cycle enzymes, and potential therapeutic opportunities for targeting the TCA cycle in cancer cells. With the application of advanced technology and in vivo model organism studies, it is our hope that studies of this previously overlooked biochemical hub will provide fresh insights into cancer metabolism and tumorigenesis, subsequently revealing vulnerabilities for therapeutic interventions in various cancer types.

Disinfection byproduct formation during biofiltration cycle: Implications for drinking water production.

Science.gov (United States)

Delatolla, R; Séguin, C; Springthorpe, S; Gorman, E; Campbell, A; Douglas, I

2015-10-01

The goal of this study was to investigate the potential of biofiltration to reduce the formation potential of disinfection byproducts (DBPs). Particularly, the work investigates the effect of the duration of the filter cycle on the formation potential of total trihalomethanes (TTHM) and five species of haloacetic acids (HAA5), dissolved oxygen (DO), organic carbon, nitrogen and total phosphorous concentrations along with biofilm coverage of the filter media and biomass viability of the attached cells. The study was conducted on a full-scale biologically active filter, with anthracite and sand media, at the Britannia water treatment plant (WTP), located in Ottawa, Ontario, Canada. The formation potential of both TTHMs and HAA5s decreased due to biofiltration. However the lowest formation potentials for both groups of DBPs and or their precursors were observed immediately following a backwash event. Hence, the highest percent removal of DBPs was observed during the early stages of the biofiltration cycle, which suggests that a higher frequency of backwashing will reduce the formation of DBPs. Variable pressure scanning electron microscopy (VPSEM) analysis shows that biofilm coverage of anthracite and sand media increases as the filtration cycle progressed, while biomass viability analysis demonstrates that the percentage of cells attached to the anthracite and sand media also increases as the filtration cycle progresses. These results suggest that the development and growth of biofilm on the filters increases the DPB formation potential. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cell cycle regulation of hematopoietic stem or progenitor cells.

Science.gov (United States)

Hao, Sha; Chen, Chen; Cheng, Tao

2016-05-01

The highly regulated process of blood production is achieved through the hierarchical organization of hematopoietic stem cell (HSC) subsets and their progenies, which differ in self-renewal and differentiation potential. Genetic studies in mice have demonstrated that cell cycle is tightly controlled by the complex interplay between extrinsic cues and intrinsic regulatory pathways involved in HSC self-renewal and differentiation. Deregulation of these cellular programs may transform HSCs or hematopoietic progenitor cells (HPCs) into disease-initiating stem cells, and can result in hematopoietic malignancies such as leukemia. While previous studies have shown roles for some cell cycle regulators and related signaling pathways in HSCs and HPCs, a more complete picture regarding the molecular mechanisms underlying cell cycle regulation in HSCs or HPCs is lacking. Based on accumulated studies in this field, the present review introduces the basic components of the cell cycle machinery and discusses their major cellular networks that regulate the dormancy and cell cycle progression of HSCs. Knowledge on this topic would help researchers and clinicians to better understand the pathogenesis of relevant blood disorders and to develop new strategies for therapeutic manipulation of HSCs.

Integral Fast Reactor Program annual progress report, FY 1991

International Nuclear Information System (INIS)

1992-06-01

This report summarizes highlights of the technical progress made in the Integral Fast Reactor (IFR) Program in FY 1991. Technical accomplishments are presented in the following areas of the IFR technology development activities: (1) metal fuel performance, (2) pyroprocess development, (3) safety experiments and analyses, (4) core design development, (5) fuel cycle demonstration, and (6) LMR technology R ampersand D

AECL's progress in developing the DUPIC fuel fabrication process

International Nuclear Information System (INIS)

Sullivan, J.D.; Cox, D.S.

1995-01-01

Spent Pressurized Water Reactor (PWR) fuel can be used directly in CANDU reactors without the need for wet chemical reprocessing or reenrichment. Considerable experimental progress has been made in verifying the practicality of this fuel cycle, including hot-cell experiments using spent PWR fuels and out-cell trials using surrogate fuels. This paper describes the current status of these experiments. (author)

Integral Fast Reactor Program. Annual progress report, FY 1993

Energy Technology Data Exchange (ETDEWEB)

Chang, Y.I.; Walters, L.C.; Laidler, J.J.; Pedersen, D.R.; Wade, D.C.; Lineberry, M.J.

1994-10-01

This report summarizes highlights of the technical progress made in the Integral Fast Reactor (IFR) Program in FY 1993. Technical accomplishments are presented in the following areas of the IFR technology development activities: (1) metal fuel performance, (2) pyroprocess development, (3) safety experiments and analyses, (4) core design development, (5) fuel cycle demonstration, and (6) LMR technology R and D.

Integral Fast Reactor Program. Annual progress report, FY 1993

International Nuclear Information System (INIS)

Chang, Y.I.; Walters, L.C.; Laidler, J.J.; Pedersen, D.R.; Wade, D.C.; Lineberry, M.J.

1994-10-01

This report summarizes highlights of the technical progress made in the Integral Fast Reactor (IFR) Program in FY 1993. Technical accomplishments are presented in the following areas of the IFR technology development activities: (1) metal fuel performance, (2) pyroprocess development, (3) safety experiments and analyses, (4) core design development, (5) fuel cycle demonstration, and (6) LMR technology R and D

Understanding cell cycle and cell death regulation provides novel weapons against human diseases.

Science.gov (United States)

Wiman, K G; Zhivotovsky, B

2017-05-01

Cell division, cell differentiation and cell death are the three principal physiological processes that regulate tissue homoeostasis in multicellular organisms. The growth and survival of cells as well as the integrity of the genome are regulated by a complex network of pathways, in which cell cycle checkpoints, DNA repair and programmed cell death have critical roles. Disruption of genomic integrity and impaired regulation of cell death may both lead to uncontrolled cell growth. Compromised cell death can also favour genomic instability. It is becoming increasingly clear that dysregulation of cell cycle and cell death processes plays an important role in the development of major disorders such as cancer, cardiovascular disease, infection, inflammation and neurodegenerative diseases. Research achievements in these fields have led to the development of novel approaches for treatment of various conditions associated with abnormalities in the regulation of cell cycle progression or cell death. A better understanding of how cellular life-and-death processes are regulated is essential for this development. To highlight these important advances, the Third Nobel Conference entitled 'The Cell Cycle and Cell Death in Disease' was organized at Karolinska Institutet in 2016. In this review we will summarize current understanding of cell cycle progression and cell death and discuss some of the recent advances in therapeutic applications in pathological conditions such as cancer, neurological disorders and inflammation. © 2017 The Association for the Publication of the Journal of Internal Medicine.

A Guide to Studying Human Hair Follicle Cycling In Vivo.

Science.gov (United States)

Oh, Ji Won; Kloepper, Jennifer; Langan, Ewan A; Kim, Yongsoo; Yeo, Joongyeub; Kim, Min Ji; Hsi, Tsai-Ching; Rose, Christian; Yoon, Ghil Suk; Lee, Seok-Jong; Seykora, John; Kim, Jung Chul; Sung, Young Kwan; Kim, Moonkyu; Paus, Ralf; Plikus, Maksim V

2016-01-01

Hair follicles (HFs) undergo lifelong cyclical transformations, progressing through stages of rapid growth (anagen), regression (catagen), and relative "quiescence" (telogen). Given that HF cycling abnormalities underlie many human hair growth disorders, the accurate classification of individual cycle stages within skin biopsies is clinically important and essential for hair research. For preclinical human hair research purposes, human scalp skin can be xenografted onto immunocompromised mice to study human HF cycling and manipulate long-lasting anagen in vivo. Although available for mice, a comprehensive guide on how to recognize different human hair cycle stages in vivo is lacking. In this article, we present such a guide, which uses objective, well-defined, and reproducible criteria, and integrates simple morphological indicators with advanced, (immuno)-histochemical markers. This guide also characterizes human HF cycling in xenografts and highlights the utility of this model for in vivo hair research. Detailed schematic drawings and representative micrographs provide examples of how best to identify human HF stages, even in suboptimally sectioned tissue, and practical recommendations are given for designing human-on-mouse hair cycle experiments. Thus, this guide seeks to offer a benchmark for human hair cycle stage classification, for both hair research experts and newcomers to the field. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

The functional role for condensin in the regulation of chromosomal organization during the cell cycle.

Science.gov (United States)

Kagami, Yuya; Yoshida, Kiyotsugu

2016-12-01

In all organisms, the control of cell cycle progression is a fundamental process that is essential for cell growth, development, and survival. Through each cell cycle phase, the regulation of chromatin organization is essential for natural cell proliferation and maintaining cellular homeostasis. During mitosis, the chromatin morphology is dramatically changed to have a "thread-like" shape and the condensed chromosomes are segregated equally into two daughter cells. Disruption of the mitotic chromosome architecture physically impedes chromosomal behaviors, such as chromosome alignment and chromosome segregation; therefore, the proper mitotic chromosome structure is required to maintain chromosomal stability. Accumulating evidence has demonstrated that mitotic chromosome condensation is induced by condensin complexes. Moreover, recent studies have shown that condensin also modulates interphase chromatin and regulates gene expression. This review mainly focuses on the molecular mechanisms that condensin uses to exert its functions during the cell cycle progression. Moreover, we discuss the condensin-mediated chromosomal organization in cancer cells.

Few-cycle isolated attosecond pulses

International Nuclear Information System (INIS)

Sansone, G.; Benedetti, E.; Calegari, F.; Stagira, S.; Vozzi, C.; Silvestri De, S.; Nisoli, M.

2006-01-01

Complete test of publication follows. In the last few years the field of attosecond science has shown impressive and rapid progress, mainly due to the introduction of novel experimental methods for the characterization of extreme ultraviolet (XUV) pulses and attosecond electron wave packets. This development has been also triggered by significant improvements in the control of the electric field of the driving infrared pulses. Particularly interesting for the applications is the generation of isolated attosecond XUV pulses using few-cycle driving pulses. In this case significant progresses have been achieved thanks to the stabilization of the carrier-envelope phase (CEP) of amplified light pulses. In this work we demonstrate that the polarization gating (PG) method with few-cycle phase-stabilized driving pulses allows one to generate few-cycle isolated attosecond pulses tunable on a very broad spectral region. The PG method is based on temporal modulation of the ellipticity of a light pulse, which confines the XUV emission in the temporal gate where the polarization is close to linear. The time-dependent polarization of phase-stabilized sub-6-fs pulses, generated by the hollow fiber technique, has been obtained using two birefringent plates. It is possible to create a linear polarization gate, whose position is imposed by the intensity profile of the pulse whilst the emission time is linked to the CEP of the electric field. The pulses have been analyzed by using a flat-field spectrometer. Continuous XUV spectra, corresponding to the production of isolated attosecond pulses, have been generated for particular CEP values. Upon changing the rotation of the first plate it was possible to tune the XUV emission in a broad spectra range. We have then achieved a complete temporal characterization of the generated isolated attosecond pulses using frequency-resolved optical gating for complete reconstruction of attosecond bursts (FROG CRAB). The measured parabolic phase

Phase II study of radiopeptide {sup 177}Lu-octreotate and capecitabine therapy of progressive disseminated neuroendocrine tumours

Energy Technology Data Exchange (ETDEWEB)

Claringbold, Phillip G. [Fremantle Hospital, Department of Oncology, Fremantle, WA (Australia); Brayshaw, Paul A.; Turner, J.H. [University of Western Australia, Department of Nuclear Medicine, Fremantle Hospital, Fremantle, WA (Australia); Price, Richard A. [Fremantle Hospital, Department of Radiology, Fremantle, WA (Australia)

2011-02-15

In this phase II study we investigated the safety and efficacy of combination capecitabine and {sup 177}Lu-octreotate for the treatment of disseminated, progressive, unresectable neuroendocrine tumours (NETs). Enrolled in the study were 33 patients with biopsy-proven NETs, positive {sup 111}In-octreotide scintigraphy and progressive disease measurable by CT/MRI who were to receive four cycles of 7.8 GBq {sup 177}Lu-octreotate 8-weekly, with 14 days of 1,650 mg/m{sup 2} capecitabine per day. Of the 33 patients, 25 completed four cycles. Minimal transient myelosuppression at 3-4 weeks caused grade 3 thrombocytopenia in one patient but no neutropenia. Nephrotoxicity was absent. Critical organ radiation dosimetry provided median estimates of the dose per cycle to the kidneys of 2.4 Gy and to the liver of 4.8 Gy, and showed cumulative doses all below toxic thresholds. Objective response rates (ORR) were 24% partial response (PR), 70% stable disease (SD) and 6% progressive disease. Median progression-free survival and median overall survival had not been reached at a median follow-up of 16 months (range 5-33 months). Survival at 1 and 2 years was 91% (95% CI 75-98%) and 88% (95% CI 71-96%), respectively. The addition of capecitabine radiosensitizing chemotherapy does not increase the minimal toxicity of {sup 177}Lu-octreotate radiopeptide therapy and led to an ORR of 24% PR and 70% minor response or SD in patients with progressive metastatic NETs. Tumour control and stabilization of disease was obtained in 94% of these patients. (orig.)

Development of FBR cycle data base system

International Nuclear Information System (INIS)

Kubota, Sadae; Ohtaki, Akira; Hirao, Kazuhiro

2002-06-01

In the 'Feasibility Study on Commercialized Fast Reactor Cycle System (F/S)'. scenario evaluations, cost-benefit evaluations and system characteristic evaluations to show significance of the Fast Breeder Reactor (FBR) cycle system introduction concretely are performed in parallel with a design study for FBR plants, reprocessing systems and fabrication systems. In these evaluations, informations such as economic prospects, prospects for supply and demand of resources and a progress of engineering development are used in addition to design information. This report explains a FBR Cycle Database in order to carry out management and search of various design information and the relating information. The prototype system of the database was completed in the 2000 fiscal year, and the problem of the user number restriction of the prototype system has been improved by Web-ization in the 2001 fiscal year. About 7,000 data are stored in this data base (as of the end of March, 2002). The expansion of user etc., and the continuation of input work of various evaluation information will be carried out, in the phase 2 of F/S. (author)

Maid (GCIP) is involved in cell cycle control of hepatocytes

DEFF Research Database (Denmark)

Sonnenberg-Riethmacher, Eva; Wüstefeld, Torsten; Miehe, Michaela

2007-01-01

. Therefore, we studied the role of Maid during cell cycle progression after partial hepatectomy (PH). Lack of Maid expression after PH was associated with a delay in G1/S-phase progression as evidenced by delayed cyclinA expression and DNA replication in Maid-deficient mice. However, at later time points......The function of Maid (GCIP), a cyclinD-binding helix-loop-helix protein, was analyzed by targeted disruption in mice. We show that Maid function is not required for normal embryonic development. However, older Maid-deficient mice-in contrast to wild-type controls--develop hepatocellular carcinomas...

Cell cycle regulation in human embryonic stem cells: links to adaptation to cell culture.

Science.gov (United States)

Barta, Tomas; Dolezalova, Dasa; Holubcova, Zuzana; Hampl, Ales

2013-03-01

Cell cycle represents not only a tightly orchestrated mechanism of cell replication and cell division but it also plays an important role in regulation of cell fate decision. Particularly in the context of pluripotent stem cells or multipotent progenitor cells, regulation of cell fate decision is of paramount importance. It has been shown that human embryonic stem cells (hESCs) show unique cell cycle characteristics, such as short doubling time due to abbreviated G1 phase; these properties change with the onset of differentiation. This review summarizes the current understanding of cell cycle regulation in hESCs. We discuss cell cycle properties as well as regulatory machinery governing cell cycle progression of undifferentiated hESCs. Additionally, we provide evidence that long-term culture of hESCs is accompanied by changes in cell cycle properties as well as configuration of several cell cycle regulatory molecules.

Rho proteins − the key regulators of cytoskeleton in the progression of mitosis and cytokinesis

Directory of Open Access Journals (Sweden)

Anna Klimaszewska

2011-11-01

Full Text Available The Rho proteins are members of the Ras superfamily of small GTPases. They are thought to be crucial regulators of multiple signal transduction pathways that influence a wide range of cellular functions, including migration, membrane trafficking, adhesion, polarity and cell shape changes. Thanks to their ability to control the assembly and organization of the actin and microtubule cytoskeletons, Rho GTPases are known to regulate mitosis and cytokinesis progression. These proteins are required for formation and rigidity of the cortex during mitotic cell rounding, mitotic spindle formation and attachment of the spindle microtubules to the kinetochore. In addition, during cytokinesis, they are involved in promoting division plane determination, contractile ring and cleavage furrow formation and abscission. They are also known as regulators of cell cycle progression at the G1/S and G2/M transition. Thus, the signal transduction pathways in which Rho proteins participate, appear to connect dynamics of actin and microtubule cytoskeletons to cell cycle progression. We review the current state of knowledge concerning the molecular mechanisms by which Rho GTPase signaling regulates remodeling of actin and microtubule cytoskeletons in order to control cell division progression.

New approaches to business cycle theory in current economic science

Directory of Open Access Journals (Sweden)

Monica DOBRESCU

2012-07-01

Full Text Available In modern economies, current research generally acknowledges that the central issues in macroeconomics are essentially the same as those identified by Keynes in the General Theory of Employment, Interest and Money. One way or the other, economists are trying to address the same macroeconomic issues that they did seven decades ago: How can we account for the different growth rates and various fluctuations observed in national economies? Which are the economic policies most suitable to solve the issues of growth and cyclic behavior? Both the new classicals and the new Keynesians have made considerable progress within their research paradigms: to explain economic fluctuations, the new classicals focus on technological perturbations, the intertemporal substitution of leisure and real business cycles; on the other hand, the new Keynesians speak in terms of monopolistic competition, menu costs or efficiency wages. On the whole, the new classicals believe that the business cycle can best be understood within the market-clearing model, whereas the new keynesians believe that business fluctuations are due to certain market failures of various sorts.The present paper focuses on the main directions of research of the new classical school on the business cycle, given that the theoretical progress in this field has been significant and relevant for economic policy during the past four decades.

Research Needs and Challenges from Science to Decision Support. Lesson Learnt from the Development of the International Reference Life Cycle Data System (ILCD) Recommendations for Life Cycle Impact Assessment

DEFF Research Database (Denmark)

Sala, Serenella; Pant, Rana; Hauschild, Michael Zwicky

2012-01-01

Environmental implications of the whole supply-chain of products, both goods and services, their use, and waste management, i.e., their entire life cycle from "cradle to grave" have to be considered to achieve more sustainable production and consumption patterns. Progress toward environmental...... sustainability requires enhancing the methodologies for quantitative, integrated environmental assessment and promoting the use of these methodologies in different domains. In the context of Life Cycle Assessment (LCA) of products, in recent years, several methodologies have been developed for Life Cycle Impact...... Assessment (LCIA). The Joint Research Center of the European Commission (EC-JRC) led a "science to decision support" process which resulted in the International Reference Life Cycle Data System (ILCD) Handbook, providing guidelines to the decision and application of methods for LCIA. The Handbook...

Investigators share improved understanding of the North American carbon cycle

Science.gov (United States)

Richard A. Birdsey; Robert Cook; Scott Denning; Peter Griffith; Beverly Law; Jeffrey Masek; Anna Michalak; Stephen Ogle; Dennis Ojima; Yude Pan; Christopher Sabine; Edwin Sheffner; Eric Sundquist

2007-01-01

The U.S. North American Carbon Program (NACP) sponsored an "all-scientist" meeting to review progress in understanding the dynamics of the carbon cycle of North American and adjacent oceans, and to chart a course for improved integration across scientifi c disciplines, scales, and Earth system boundaries. The meeting participants also addressed the need for...

Genomic analysis reveals a potential role for cell cycle perturbation in HCV-mediated apoptosis of cultured hepatocytes.

Directory of Open Access Journals (Sweden)

Kathie-Anne Walters

2009-01-01

Full Text Available The mechanisms of liver injury associated with chronic HCV infection, as well as the individual roles of both viral and host factors, are not clearly defined. However, it is becoming increasingly clear that direct cytopathic effects, in addition to immune-mediated processes, play an important role in liver injury. Gene expression profiling during multiple time-points of acute HCV infection of cultured Huh-7.5 cells was performed to gain insight into the cellular mechanism of HCV-associated cytopathic effect. Maximal induction of cell-death-related genes and appearance of activated caspase-3 in HCV-infected cells coincided with peak viral replication, suggesting a link between viral load and apoptosis. Gene ontology analysis revealed that many of the cell-death genes function to induce apoptosis in response to cell cycle arrest. Labeling of dividing cells in culture followed by flow cytometry also demonstrated the presence of significantly fewer cells in S-phase in HCV-infected relative to mock cultures, suggesting HCV infection is associated with delayed cell cycle progression. Regulation of numerous genes involved in anti-oxidative stress response and TGF-beta1 signaling suggest these as possible causes of delayed cell cycle progression. Significantly, a subset of cell-death genes regulated during in vitro HCV infection was similarly regulated specifically in liver tissue from a cohort of HCV-infected liver transplant patients with rapidly progressive fibrosis. Collectively, these data suggest that HCV mediates direct cytopathic effects through deregulation of the cell cycle and that this process may contribute to liver disease progression. This in vitro system could be utilized to further define the cellular mechanism of this perturbation.

Cell Cycle Control in the Early Embryonic Development of Aquatic Animal Species

Science.gov (United States)

Siefert, Joseph C.; Clowdus, Emily A.; Sansam, Christopher L.

2016-01-01

The cell cycle is integrated with many aspects of embryonic development. Not only is proper control over the pace of cell proliferation important, but also the timing of cell cycle progression is coordinated with transcription, cell migration, and cell differentiation. Due to the ease with which the embryos of aquatic organisms can be observed and manipulated, they have been a popular choice for embryologists throughout history. In the cell cycle field, aquatic organisms have been extremely important because they have played a major role in the discovery and analysis of key regulators of the cell cycle. In particular, the frog Xenopus laevis has been instrumental for understanding how the basic embryonic cell cycle is regulated. More recently, the zebrafish has been used to understand how the cell cycle is remodeled during vertebrate development and how it is regulated during morphogenesis. This review describes how some of the unique strengths of aquatic species have been leveraged for cell cycle research and suggests how species such as Xenopus and zebrafish will continue to reveal the roles of the cell cycle in human biology and disease. PMID:26475527

Functional cooperation between FACT and MCM is coordinated with cell cycle and differential complex formation

Directory of Open Access Journals (Sweden)

Lin Chih-Li

2010-02-01

Full Text Available Abstract Background Functional cooperation between FACT and the MCM helicase complex constitutes an integral step during DNA replication initiation. However, mode of regulation that underlies the proper functional interaction of FACT and MCM is poorly understood. Methods & Results Here we present evidence indicating that such interaction is coordinated with cell cycle progression and differential complex formation. We first demonstrate the existence of two distinct FACT-MCM subassemblies, FACT-MCM2/4/6/7 and FACT-MCM2/3/4/5. Both complexes possess DNA unwinding activity and are subject to cell cycle-dependent enzymatic regulation. Interestingly, analysis of functional attributes further suggests that they act at distinct, and possibly sequential, steps during origin establishment and replication initiation. Moreover, we show that the phosphorylation profile of the FACT-associated MCM4 undergoes a cell cycle-dependent change, which is directly correlated with the catalytic activity of the FACT-MCM helicase complexes. Finally, at the quaternary structure level, physical interaction between FACT and MCM complexes is generally dependent on persistent cell cycle and further stabilized upon S phase entry. Cessation of mitotic cycle destabilizes the complex formation and likely leads to compromised coordination and activities. Conclusions Together, our results correlate FACT-MCM functionally and temporally with S phase and DNA replication. They further demonstrate that enzymatic activities intrinsically important for DNA replication are tightly controlled at various levels, thereby ensuring proper progression of, as well as exit from, the cell cycle and ultimately euploid gene balance.

UV-induced changes in cell cycle and gene expression within rabbit lens epithelial cells

International Nuclear Information System (INIS)

Sidjanin, D.; Grdina, D.; Woloschak, G.E.

1996-01-01

Damage to lens epithelial cells is a probable initiation process in cataract formation mediated by UV radiation. In these experiments, we investigated the effects of exposure to 254 nm radiation on cell cycle progression in the rabbit lens epithelial cell line N/N1003A. The RNA was harvested at various times following exposure to UV (254 nm) radiation and analyzed by dot-blot and northern blot hybridizations. These results revealed that during the first 6 h following exposure of the cells to UV, there was, associated with decreasing dose, a decrease in accumulation of transcripts specific for histones H3 and H4 and an increase in the mRNA encoding protein kinase C and β- and γ-actin. Using flow cytometry, we detected an accumulation of cells in G1/S phase of the cell cycle 1 h following exposure to 254 nm radiation. The observed changes in gene expression, especially the decreased accumulation of histone transcripts reported here, may play a role in UV-induced inhibition of cell cycle progression. (Author)

High-temperature gas-cooled reactor steam cycle/cogeneration application study update

International Nuclear Information System (INIS)

1981-09-01

Since publication of a report on the application of a High Temperature Gas-Cooled Reactor Steam Cycle/Cogeneration (HTGR-SC/C) plant in December of 1980, progress has continued on application related activities. In particular, a reference plant and an application identification effort has been performed, a variable cogeneration cycle balance-of-plant design was developed and an updated economic analysis was prepared. A reference HTGR-SC/C plant size of 2240 MW(t) was selected, primarily on the basis of 2240 MW(t) being in the mid-range of anticipated application needs and the availability of the design data from the 2240 MW(t) Steam Cycle/Electric generation plant design. A variable cogeneration cycle plant design was developed having the capability of operating at a range of process steam loads between the reference design load (full cogeneration) and the no process steam load condition

Cell cycle arrest and the evolution of chronic kidney disease from acute kidney injury.

Science.gov (United States)

Canaud, Guillaume; Bonventre, Joseph V

2015-04-01

For several decades, acute kidney injury (AKI) was generally considered a reversible process leading to complete kidney recovery if the individual survived the acute illness. Recent evidence from epidemiologic studies and animal models, however, have highlighted that AKI can lead to the development of fibrosis and facilitate the progression of chronic renal failure. When kidney injury is mild and baseline function is normal, the repair process can be adaptive with few long-term consequences. When the injury is more severe, repeated, or to a kidney with underlying disease, the repair can be maladaptive and epithelial cell cycle arrest may play an important role in the development of fibrosis. Indeed, during the maladaptive repair after a renal insult, many tubular cells that are undergoing cell division spend a prolonged period in the G2/M phase of the cell cycle. These tubular cells recruit intracellular pathways leading to the synthesis and the secretion of profibrotic factors, which then act in a paracrine fashion on interstitial pericytes/fibroblasts to accelerate proliferation of these cells and production of interstitial matrix. Thus, the tubule cells assume a senescent secretory phenotype. Characteristic features of these cells may represent new biomarkers of fibrosis progression and the G2/M-arrested cells may represent a new therapeutic target to prevent, delay or arrest progression of chronic kidney disease. Here, we summarize recent advances in our understanding of the biology of the cell cycle and how cell cycle arrest links AKI to chronic kidney disease. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Strategic cycling: shaking complacency in healthcare strategic planning.

Science.gov (United States)

Begun, J; Heatwole, K B

1999-01-01

As the conditions affecting business and healthcare organizations in the United States have become more turbulent and uncertain, strategic planning has decreased in popularity. Strategic planning is criticized for stiffling creative responses to the new marketplace and for fostering compartmentalized organizations, adherence to outmoded strategies, tunnel vision in strategy formulation, and overemphasis on planning to the detriment of implementation. However, effective strategic planning can be a force for mobilizing all the constituents of an organization, creating discipline in pursuit of a goal, broadening an organization's perspective, improving communication among disciplines, and motivating the organization's workforce. It is worthwhile for healthcare organizations to preserve these benefits of strategic planning at the same time recognizing the many sources of turbulence and uncertainty in the healthcare environment. A model of "strategic cycling" is presented to address the perceived shortcomings of traditional strategic planning in a dynamic environment. The cycling model facilitates continuous assessment of the organization's mission/values/vision and primary strategies based on feedback from benchmark analysis, shareholder impact, and progress in strategy implementation. Multiple scenarios and contingency plans are developed in recognition of the uncertain future. The model represents a compromise between abandoning strategic planning and the traditional, linear model of planning based on progress through predetermined stages to a masterpiece plan.

The p75{sup NTR} tumor suppressor induces cell cycle arrest facilitating caspase mediated apoptosis in prostate tumor cells

Energy Technology Data Exchange (ETDEWEB)

Khwaja, Fatima [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University Medical Center, Washington, DC 20057-1436 (United States); Tabassum, Arshia [Toronto Western Hospital, Toronto, ON, M5T258 (Canada); Allen, Jeff [National Center for Complementary and Alternative Medicine, N.I.H., Bethesda, MD 20892 (United States); Djakiew, Daniel [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University Medical Center, Washington, DC 20057-1436 (United States) and Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057-1436 (United States)

2006-03-24

The p75 neurotrophin receptor (p75{sup NTR}) is a death receptor which belongs to the tumor necrosis factor receptor super-family of membrane proteins. This study shows that p75{sup NTR} retarded cell cycle progression by induced accumulation of cells in G0/G1 and a reduction in the S phase of the cell cycle. The rescue of tumor cells from cell cycle progression by a death domain deleted ({delta}DD) dominant-negative antagonist of p75{sup NTR} showed that the death domain transduced anti-proliferative activity in a ligand-independent manner. Conversely, addition of NGF ligand rescued retardation of cell cycle progression with commensurate changes in components of the cyclin/cdk holoenzyme complex. In the absence of ligand, p75{sup NTR}-dependent cell cycle arrest facilitated an increase in apoptotic nuclear fragmentation of the prostate cancer cells. Apoptosis of p75{sup NTR} expressing cells occurred via the intrinsic mitochondrial pathway leading to a sequential caspase-9 and -7 cascade. Since the death domain deleted dominant-negative antagonist of p75{sup NTR} rescued intrinsic caspase associated apoptosis in PC-3 cells, this shows p75{sup NTR} was integral to ligand independent induction of apoptosis. Moreover, the ability of ligand to ameliorate the p75{sup NTR}-dependent intrinsic apoptotic cascade indicates that NGF functioned as a survival factor for p75{sup NTR} expressing prostate cancer cells.

Psychosocial Implications of Usher Syndrome, Type I, throughout the Life Cycle.

Science.gov (United States)

Miner, I. D.

1995-01-01

Usher syndrome, Type I, requires multiple adaptations throughout the life cycle because each stage of life has tasks and losses associated with deafness and progressive retinitis pigmentosa. This article examines the issues raised at each stage, using clinical vignettes from persons who have this condition and their families. (Author/DB)

Comparison of Engine Cycle Codes for Rocket-Based Combined Cycle Engines

Science.gov (United States)

Waltrup, Paul J.; Auslender, Aaron H.; Bradford, John E.; Carreiro, Louis R.; Gettinger, Christopher; Komar, D. R.; McDonald, J.; Snyder, Christopher A.

2002-01-01

This paper summarizes the results from a one day workshop on Rocket-Based Combined Cycle (RBCC) Engine Cycle Codes held in Monterey CA in November of 2000 at the 2000 JANNAF JPM with the authors as primary participants. The objectives of the workshop were to discuss and compare the merits of existing Rocket-Based Combined Cycle (RBCC) engine cycle codes being used by government and industry to predict RBCC engine performance and interpret experimental results. These merits included physical and chemical modeling, accuracy and user friendliness. The ultimate purpose of the workshop was to identify the best codes for analyzing RBCC engines and to document any potential shortcomings, not to demonstrate the merits or deficiencies of any particular engine design. Five cases representative of the operating regimes of typical RBCC engines were used as the basis of these comparisons. These included Mach 0 sea level static and Mach 1.0 and Mach 2.5 Air-Augmented-Rocket (AAR), Mach 4 subsonic combustion ramjet or dual-mode scramjet, and Mach 8 scramjet operating modes. Specification of a generic RBCC engine geometry and concomitant component operating efficiencies, bypass ratios, fuel/oxidizer/air equivalence ratios and flight dynamic pressures were provided. The engine included an air inlet, isolator duct, axial rocket motor/injector, axial wall fuel injectors, diverging combustor, and exit nozzle. Gaseous hydrogen was used as the fuel with the rocket portion of the system using a gaseous H2/O2 propellant system to avoid cryogenic issues. The results of the workshop, even after post-workshop adjudication of differences, were surprising. They showed that the codes predicted essentially the same performance at the Mach 0 and I conditions, but progressively diverged from a common value (for example, for fuel specific impulse, Isp) as the flight Mach number increased, with the largest differences at Mach 8. The example cases and results are compared and discussed in this paper.

Globalization of the nuclear fuel cycle impact of developments on fuel management

Energy Technology Data Exchange (ETDEWEB)

Van Den Durpel, L.; Bertel, E. [OCDE-NEA, Nuclear Development Div., 92 - Issy-les-Moulineaux (France)

1999-07-01

Nuclear energy will have to cope more and more with a rapid changing environment due to economic competitive pressure and the de-regulatory progress. In current economic environment, utilities will have to focus strongly on the reduction of their total generation costs, covering the fuel cycle costs, which are only partly under their control. Developments in the fuel cycle will be in the short-term rather evolutionary addressing the current needs of utilities. However, within the context of sustainable development and more and more inclusion of externalities in energy generation costs, more performing developments in the fuel cycle could become important and feasible. A life-cycle design approach of the fuel cycle will be requested in order to cover all factors in order to decrease significantly the nuclear energy generation cost to compete with other alternative fuels in the long-term. This paper will report on some of the trends one could distinguish in the fuel cycle with emphasis on cost reduction. OECD/NEA is currently conducting a study on the fuel cycle aiming to assess current and future nuclear fuel cycles according the potential for further improvement of the full added-value chain of these cycles from a mainly technological and economical perspective including environmental and social considerations. (authors)

Globalisation of the nuclear fuel cycle - impact of developments on fuel management

International Nuclear Information System (INIS)

Durpel, L. van den; Bertel, E.

2000-01-01

Nuclear energy will have to cope more and more with a rapid changing environment due to economic competitive pressure and the deregulatory progress. In current economic environment, utilities will have to focus strongly on the reduction of their total generation costs, covering the fuel cycle costs, which are only partly under their control. Developments in the fuel cycle will be in the short-term rather evolutionary addressing the current needs of utilities. However, within the context of sustainable development and more and more inclusion of externalities in energy generation costs, more performing developments in the fuel cycle could become important and feasible. A life-cycle design approach of the fuel cycle will be requested in order to cover all factors in order to decrease significantly the nuclear energy generation cost to complete with other alternative fuels in the long-term. This paper will report on some of the trends one could distinguish in the fuel cycle with emphasis on cost reduction. OECD/NEA is currently conducting a study on the fuel cycle aiming to assess current and future nuclear fuel cycles according to the potential for further improvement of the full added-value chain of these cycles from a mainly technological and economic perspective including environmental and social considerations. (orig.) [de

Chloroplast Dysfunction Causes Multiple Defects in Cell Cycle Progression in the Arabidopsis crumpled leaf Mutant

KAUST Repository

Hudik, Elodie; Yoshioka, Yasushi; Domenichini, Sé Verine; Bourge, Mickaë l; Soubigout-Taconnat, Ludivine; Mazubert, Christelle; Yi, Dalong; Bujaldon, Sandrine; Hayashi, Hiroyuki; De Veylder, Lieven; Bergounioux, Catherine; Benhamed, Moussa; Raynaud, Cé cile

2014-01-01

The majority of research on cell cycle regulation is focused on the nuclear events that govern the replication and segregation of the genome between the two daughter cells. However, eukaryotic cells contain several compartmentalized organelles

CANDU fuel cycle options in Korea

International Nuclear Information System (INIS)

Boczar, P.G.; Fehrenbach, P.J.; Meneley, D.A.

1996-04-01

The easiest first step in CANDU fuel-cycle evolution may be the use of slightly enriched uranium (SEU), including recovered uranium from reprocessed LWR spent fuel. Relatively low enrichment (up to 1.2%) will result in a twoto three-fold reduction in the quantity of spent fuel per unit energy production, reductions in fuel-cycle costs, and greater flexibility in the design of new reactors. The CANFLEX (CANDU FLEXible) fuel bundle would be the optimal fuel carrier. A country that has both CANDU and PWR reactors can exploit the natural synergism between these two reactor types to minimize overall waste production, and maximize energy derived from the fuel. This synergism can be exploited through several different fuel cycles. A high burnup CANDU MOX fuel design could be used to utilize plutonium from conventional reprocessing or more advanced reprocessing options (such as co-processing). DUPIC (Direct Use of Spent PWR Fuel In CANDU) represents a recycle option that has a higher degree of proliferation resistance than does conventional reprocessing, since it uses only dry processes for converting spent PWR fuel into CANDU fuel, without separating the plutonium. Good progress is being made in the current KAERI, AECL, and U.S. Department of State program in demonstrating the technical feasibility of DUPIC. In the longer term, CANDU reactors offer even more dramatic synergistic fuel cycles with PWR or FBR reactors. If the objective of a national fuel-cycle program is the minimization of actinide waste or destruction of long-lived fission products, then studies have shown the superiority of CANDU reactors in meeting this objective. Long-term energy security can be assured either through the thorium cycle or through a CANDU 1 FBR system, in which the FBR would be operated as a 'fuel factory,' providing the fissile material to power a number of lower-cost, high efficiency CANDU reactors. In summary, the CANDU reactor's simple fuel design, high neutron economy, and on

Glucose capped silver nanoparticles induce cell cycle arrest in HeLa cells.

Science.gov (United States)

Panzarini, Elisa; Mariano, Stefania; Vergallo, Cristian; Carata, Elisabetta; Fimia, Gian Maria; Mura, Francesco; Rossi, Marco; Vergaro, Viviana; Ciccarella, Giuseppe; Corazzari, Marco; Dini, Luciana

2017-06-01

This study aims to determine the interaction (uptake and biological effects on cell viability and cell cycle progression) of glucose capped silver nanoparticles (AgNPs-G) on human epithelioid cervix carcinoma (HeLa) cells, in relation to amount, 2×10 3 or 2×10 4 NPs/cell, and exposure time, up to 48h. The spherical and well dispersed AgNPs (30±5nm) were obtained by using glucose as reducing agent in a green synthesis method that ensures to stabilize AgNPs avoiding cytotoxic soluble silver ions Ag + release. HeLa cells take up abundantly and rapidly AgNPs-G resulting toxic to cells in amount and incubation time dependent manner. HeLa cells were arrested at S and G2/M phases of the cell cycle and subG1 population increased when incubated with 2×10 4 AgNPs-G/cell. Mitotic index decreased accordingly. The dissolution experiments demonstrated that the observed effects were due only to AgNPs-G since glucose capping prevents Ag + release. The AgNPs-G influence on HeLa cells viability and cell cycle progression suggest that AgNPs-G, alone or in combination with chemotherapeutics, may be exploited for the development of novel antiproliferative treatment in cancer therapy. However, the possible influence of the cell cycle on cellular uptake of AgNPs-G and the mechanism of AgNPs entry in cells need further investigation. Copyright © 2017 Elsevier B.V. All rights reserved.

Episode cycles with increasing recurrences in first-episode bipolar-I disorder patients.

Science.gov (United States)

Baldessarini, R J; Salvatore, P; Khalsa, H-M K; Imaz-Etxeberria, H; Gonzalez-Pinto, A; Tohen, M

2012-01-01

Preliminary review of a century of studies of the course of manic-depressive syndromes produced 40 reports, of which approximately one-third report evidence of shortening wellness intervals or cycle-lengths with more recurrences, and two-thirds did not. We evaluated inter-episode intervals (cycle-length) in 128 clinically-treated, DSM-IV bipolar-I disorder patients followed prospectively and systematically over 5.7 years, with 6.5 episodes/person. As expected, cycle-length varied inversely with total cycle-count/person; however, multivariate linear regression found only longer initial hospitalization and fewer total cycles to be associated with cycle-length, whereas cycle-number (1, 2, 3, etc.), sex, intake-age, and first-episode polarity were not. Regression of within-subject cycle-length versus cycle-number yielded individual slope-functions with pseudo-random distribution (28% fell within ±1 month/cycle of the null [zero-slope]). Mean duration of early and late euthymic intervals (cycles 2 vs. 5) in patients with matched recurrence-counts was nearly identical. The course of bipolar-I disorder from onset was largely random or chaotic over nearly 6 years from onset. Only a minority of patients showed either cycle-acceleration or slowing, without changes in wellness intervals. The findings may be influenced by treatment-effects, but seem to indicate that most current bipolar-I disorder patients are unlikely to show progressive shortening of recurrence-cycles. Copyright © 2011 Elsevier B.V. All rights reserved.

The brain-computer interface cycle.

Science.gov (United States)

van Gerven, Marcel; Farquhar, Jason; Schaefer, Rebecca; Vlek, Rutger; Geuze, Jeroen; Nijholt, Anton; Ramsey, Nick; Haselager, Pim; Vuurpijl, Louis; Gielen, Stan; Desain, Peter

2009-08-01

Brain-computer interfaces (BCIs) have attracted much attention recently, triggered by new scientific progress in understanding brain function and by impressive applications. The aim of this review is to give an overview of the various steps in the BCI cycle, i.e., the loop from the measurement of brain activity, classification of data, feedback to the subject and the effect of feedback on brain activity. In this article we will review the critical steps of the BCI cycle, the present issues and state-of-the-art results. Moreover, we will develop a vision on how recently obtained results may contribute to new insights in neurocognition and, in particular, in the neural representation of perceived stimuli, intended actions and emotions. Now is the right time to explore what can be gained by embracing real-time, online BCI and by adding it to the set of experimental tools already available to the cognitive neuroscientist. We close by pointing out some unresolved issues and present our view on how BCI could become an important new tool for probing human cognition.

Orchestration of DNA Damage Checkpoint Dynamics across the Human Cell Cycle.

Science.gov (United States)

Chao, Hui Xiao; Poovey, Cere E; Privette, Ashley A; Grant, Gavin D; Chao, Hui Yan; Cook, Jeanette G; Purvis, Jeremy E

2017-11-22

Although molecular mechanisms that prompt cell-cycle arrest in response to DNA damage have been elucidated, the systems-level properties of DNA damage checkpoints are not understood. Here, using time-lapse microscopy and simulations that model the cell cycle as a series of Poisson processes, we characterize DNA damage checkpoints in individual, asynchronously proliferating cells. We demonstrate that, within early G1 and G2, checkpoints are stringent: DNA damage triggers an abrupt, all-or-none cell-cycle arrest. The duration of this arrest correlates with the severity of DNA damage. After the cell passes commitment points within G1 and G2, checkpoint stringency is relaxed. By contrast, all of S phase is comparatively insensitive to DNA damage. This checkpoint is graded: instead of halting the cell cycle, increasing DNA damage leads to slower S phase progression. In sum, we show that a cell's response to DNA damage depends on its exact cell-cycle position and that checkpoints are phase-dependent, stringent or relaxed, and graded or all-or-none. Copyright © 2017 Elsevier Inc. All rights reserved.

A central to peripheral progression of cell cycle exit and hair cell differentiation in the developing mouse cristae.

Science.gov (United States)

Slowik, Amber D; Bermingham-McDonogh, Olivia

2016-03-01

The inner ear contains six distinct sensory organs that each maintains some ability to regenerate hair cells into adulthood. In the postnatal cochlea, there appears to be a relationship between the developmental maturity of a region and its ability to regenerate as postnatal regeneration largely occurs in the apical turn, which is the last region to differentiate and mature during development. In the mature cristae there are also regional differences in regenerative ability, which led us to hypothesize that there may be a general relationship between the relative maturity of a region and the regenerative competence of that region in all of the inner ear sensory organs. By analyzing adult mouse cristae labeled embryonically with BrdU, we found that hair cell birth starts in the central region and progresses to the periphery with age. Since the peripheral region of the adult cristae also maintains active Notch signaling and some regenerative competence, these results are consistent with the hypothesis that the last regions to develop retain some of their regenerative ability into adulthood. Further, by analyzing embryonic day 14.5 inner ears we provide evidence for a wave of hair cell birth along the longitudinal axis of the cristae from the central regions to the outer edges. Together with the data from the adult inner ears labeled with BrdU as embryos, these results suggest that hair cell differentiation closely follows cell cycle exit in the cristae, unlike in the cochlea where they are uncoupled. Copyright © 2016 Elsevier Inc. All rights reserved.

Is organizational progress in the EFQM model related to employee satisfaction?

Science.gov (United States)

Matthies-Baraibar, Carmen; Arcelay-Salazar, Andoni; Cantero-González, David; Colina-Alonso, Alberto; García-Urbaneja, Marbella; González-Llinares, Rosa María; Letona-Aranburu, Jon; Martínez-Carazo, Catalina; Mateos-Del Pino, Maider; Nuño-Solinís, Roberto; Olaetxea-Urizar, Esther; de la Rica-Giménez, José Antonio; Rodríguez-González, María Angeles; Dabouza-Acebal, Silvia

2014-10-24

To determine whether there is greater employee satisfaction in organisations that have made more progress in implementation of the European Foundation for Quality Management (EFQM) model. A series of cross-sectional studies (one for each assessment cycle) comparing staff satisfaction survey results between groups of healthcare organisations by degree of implementation of the EFQM model (assessed in terms of external recognition of management quality in each organisation). 30 healthcare organisations including hospitals, primary care and mental health providers in Osakidetza, the Basque public health service. Employees of 30 Osakidetza organisations. Progress in implementation of EFQM model. Scores in 9 dimensions of employee satisfaction from questionnaires administered in healthcare organisations in 4 assessment cycles between 2001 and 2010. Comparing satisfaction results in organisations granted Gold or Silver Q Awards and those without this type of external recognition, we found statistically significant differences in the dimensions of training and internal communication. Then, comparing recipients of Gold Q Awards with those with no Q Certification, differences in leadership style and in policy and strategy also emerged as significant. Progress of healthcare organisations in the implementation of the EFQM Excellence Model is associated with increases in their employee satisfaction in dimensions that can be managed at the level of each organisation, while dimensions in which no statistically significant differences were found represent common organisational elements with little scope for self-management.

Investigations on the application of zeotropic fluid mixtures in the organic rankine cycle for the geothermal power generation; Untersuchung zum Einsatz von zeotropen Fluidgemischen im Organic Rankine Cycle fuer die geothermische Stromerzeugung

Energy Technology Data Exchange (ETDEWEB)

Heberle, Florian

2013-04-01

The organic rankine cycle is a thermodynamic cycle process which uses an organic fluid working fluid instead of water in comparison to the commercial rankine process. The organic rankine cycle facilitates sufficiently high pressures at moderate temperatures. The organic rankine cycle significantly expands the technically possible and economically feasible ranges of application of such heat and power processes. The geothermal power is a very attractive field of application. Thermal water with a temperature of nearly 100 Celsius can be used for the power generation by means of the organic rankine cycle. Especially zeotropic mixtures are interesting as a working fluid. This is due to a non-isothermal phase change to a temperature glide which adapts very well to the temperature progress of the heat source. The author of the book under consideration reports on the application of different mixtures in the organic rankine cycle. The evaluation is based on a thermodynamic analysis and considers also toxicological, ecologic, technical as well as economic aspects.

Advanced nuclear fuel cycles activities in IAEA

International Nuclear Information System (INIS)

Nawada, H.P.; Ganguly, C.

2007-01-01

Full text of publication follows. Of late several developments in reprocessing areas along with advances in fuel design and robotics have led to immense interest in partitioning and transmutation (P and T). The R and D efforts in the P and T area are being paid increased attention as potential answers to ever-growing issues threatening sustainability, environmental protection and non-proliferation. Any fuel cycle studies that integrate partitioning and transmutation are also known as ''advanced fuel cycles'' (AFC), that could incinerate plutonium and minor actinide (MA) elements (namely Am, Np, Cm, etc.) which are the main contributors to long-term radiotoxicity. The R and D efforts in developing these innovative fuel cycles as well as reactors are being co-ordinated by international initiatives such as Innovative Nuclear Power Reactors and Fuel Cycles (INPRO), the Generation IV International Forum (GIF) and the Global Nuclear Energy Partnership (GENP). For these advanced nuclear fuel cycle schemes to take shape, the development of liquid-metal-cooled reactor fuel cycles would be the most essential step for implementation of P and T. Some member states are also evaluating other concepts involving the use of thorium fuel cycle or inert-matrix fuel or coated particle fuel. Advanced fuel cycle involving novel partitioning methods such as pyrochemical separation methods to recover the transuranic elements are being developed by some member states which would form a critical stage of P and T. However, methods that can achieve a very high reduction (>99.5%) of MA and long-lived fission products in the waste streams after partitioning must be achieved to realize the goal of an improved protection of the environment. In addition, the development of MA-based fuel is also an essential and crucial step for transmutation of these transuranic elements. The presentation intends to describe progress of the IAEA activities encompassing the following subject-areas: minimization of

Selenium as an essential micronutrient: roles in cell cycle and apoptosis.

Science.gov (United States)

Zeng, Huawei

2009-03-23

Selenium is an essential trace element for humans and animals, and selenium deficiency is associated with several disease conditions such as immune impairment. In addition, selenium intakes that are greater than the recommended daily allowance (RDA) appear to protect against certain types of cancers. In humans and animals, cell proliferation and death must be regulated to maintain tissue homeostasis, and it has been well documented that numerous human diseases are directly related to the control of cell cycle progression and apoptosis. Thus, the elucidation of the mechanisms by which selenium regulates the cell cycle and apoptosis can lead to a better understanding of the nature of selenium's essentiality and its role in disease prevention. This article reviews the status of knowledge concerning the effect of selenium on cell cycle and apoptosis.

Report of Nuclear Fuel Cycle Subcommittee

International Nuclear Information System (INIS)

1982-01-01

In order to secure stable energy supply over a long period of time, the development and utilization of atomic energy have been actively promoted as the substitute energy for petroleum. Accordingly, the establishment of nuclear fuel cycle is indispensable to support this policy, and efforts have been exerted to promote the technical development and to put it in practical use. The Tokai reprocessing plant has been in operation since the beginning of 1981, and the pilot plant for uranium enrichment is about to start the full scale operation. Considering the progress in the refining and conversion techniques, plutonium fuel fabrication and son on, the prospect to technically establish the nuclear fuel cycle in Japan has been bright. The important problem for the future is to put these techniques in practical use economically. The main point of technical development hereafter is the enlargement and rationalization of the techniques, and the cooperation of the government and the people, and the smooth transfer of the technical development results in public corporations to private organization are necessary. The important problems for establishing the nuclear fuel cycle, the securing of enriched uranium, the reprocessing of spent fuel, unused resources, and the problems related to industrialization, location and fuel storing are reported. (Kako, I.)

Cell Cycle Regulation by Alternative Polyadenylation of CCND1.

Science.gov (United States)

Wang, Qiong; He, Guopei; Hou, Mengmeng; Chen, Liutao; Chen, Shangwu; Xu, Anlong; Fu, Yonggui

2018-05-01

Global shortening of 3'UTRs by alternative polyadenylation (APA) has been observed in cancer cells. However, the role of APA in cancer remains unknown. CCND1 is a proto-oncogene that regulates progression through the G1-S phase of the cell cycle; moreover, it has been observed to be switching to proximal APA sites in cancer cells. To investigate the biological function of the APA of CCND1, we edited the weak poly(A) signal (PAS) of the proximal APA site to a canonical PAS using the CRISPR/Cas9 method, which can force the cells to use a proximal APA site. Cell cycle profiling and proliferation assays revealed that the proximal APA sites of CCND1 accelerated the cell cycle and promoted cell proliferation, but UTR-APA and CR-APA act via different molecular mechanisms. These results indicate that PAS editing with CRISPR/Cas9 provides a good method by which to study the biological function of APA.

A Stochastic Model of the Yeast Cell Cycle Reveals Roles for Feedback Regulation in Limiting Cellular Variability.

Science.gov (United States)

Barik, Debashis; Ball, David A; Peccoud, Jean; Tyson, John J

2016-12-01

The cell division cycle of eukaryotes is governed by a complex network of cyclin-dependent protein kinases (CDKs) and auxiliary proteins that govern CDK activities. The control system must function reliably in the context of molecular noise that is inevitable in tiny yeast cells, because mistakes in sequencing cell cycle events are detrimental or fatal to the cell or its progeny. To assess the effects of noise on cell cycle progression requires not only extensive, quantitative, experimental measurements of cellular heterogeneity but also comprehensive, accurate, mathematical models of stochastic fluctuations in the CDK control system. In this paper we provide a stochastic model of the budding yeast cell cycle that accurately accounts for the variable phenotypes of wild-type cells and more than 20 mutant yeast strains simulated in different growth conditions. We specifically tested the role of feedback regulations mediated by G1- and SG2M-phase cyclins to minimize the noise in cell cycle progression. Details of the model are informed and tested by quantitative measurements (by fluorescence in situ hybridization) of the joint distributions of mRNA populations in yeast cells. We use the model to predict the phenotypes of ~30 mutant yeast strains that have not yet been characterized experimentally.

A Stochastic Model of the Yeast Cell Cycle Reveals Roles for Feedback Regulation in Limiting Cellular Variability.

Directory of Open Access Journals (Sweden)

Debashis Barik

2016-12-01

Full Text Available The cell division cycle of eukaryotes is governed by a complex network of cyclin-dependent protein kinases (CDKs and auxiliary proteins that govern CDK activities. The control system must function reliably in the context of molecular noise that is inevitable in tiny yeast cells, because mistakes in sequencing cell cycle events are detrimental or fatal to the cell or its progeny. To assess the effects of noise on cell cycle progression requires not only extensive, quantitative, experimental measurements of cellular heterogeneity but also comprehensive, accurate, mathematical models of stochastic fluctuations in the CDK control system. In this paper we provide a stochastic model of the budding yeast cell cycle that accurately accounts for the variable phenotypes of wild-type cells and more than 20 mutant yeast strains simulated in different growth conditions. We specifically tested the role of feedback regulations mediated by G1- and SG2M-phase cyclins to minimize the noise in cell cycle progression. Details of the model are informed and tested by quantitative measurements (by fluorescence in situ hybridization of the joint distributions of mRNA populations in yeast cells. We use the model to predict the phenotypes of ~30 mutant yeast strains that have not yet been characterized experimentally.

An apoptotic cell cycle mutant in Saccharomyces cerevisiae

DEFF Research Database (Denmark)

Villadsen, Ingrid

1996-01-01

The simple eukaryote Saccharomyces cerevisiae has proved to be a useful organism for elucidating the mechanisms that govern cell cycle progression in eukaryotic cells. The excellent in vivo system permits a cell cycle study using temperature sensitive mutants. In addition, it is possible to study...... many genes and gene products from higher eukaryotes in Saccharomyces cerevisiae because many genes and biological processes are homologous or similar in lower and in higher eukaryotes. The highly developed methods of genetics and molecular biology greatly facilitates studies of higher eukaryotic...... processes.Programmmed cell death with apoptosis plays a major role in development and homeostatis in most, if not all, animal cells. Apoptosis is a morphologically distinct form of death, that requires the activation of a highly regulated suicide program. Saccharomyces cerevisiae provides a new system...

H4 histamine receptors mediate cell cycle arrest in growth factor-induced murine and human hematopoietic progenitor cells.

Directory of Open Access Journals (Sweden)

Anne-France Petit-Bertron

Full Text Available The most recently characterized H4 histamine receptor (H4R is expressed preferentially in the bone marrow, raising the question of its role during hematopoiesis. Here we show that both murine and human progenitor cell populations express this receptor subtype on transcriptional and protein levels and respond to its agonists by reduced growth factor-induced cell cycle progression that leads to decreased myeloid, erythroid and lymphoid colony formation. H4R activation prevents the induction of cell cycle genes through a cAMP/PKA-dependent pathway that is not associated with apoptosis. It is mediated specifically through H4R signaling since gene silencing or treatment with selective antagonists restores normal cell cycle progression. The arrest of growth factor-induced G1/S transition protects murine and human progenitor cells from the toxicity of the cell cycle-dependent anticancer drug Ara-C in vitro and reduces aplasia in a murine model of chemotherapy. This first evidence for functional H4R expression in hematopoietic progenitors opens new therapeutic perspectives for alleviating hematotoxic side effects of antineoplastic drugs.

Morphological and Molecular Descriptors of the Developmental Cycle of Babesia divergens Parasites in Human Erythrocytes.

Directory of Open Access Journals (Sweden)

Ingrid Rossouw

2015-05-01

Full Text Available Human babesiosis, especially caused by the cattle derived Babesia divergens parasite, is on the increase, resulting in renewed attentiveness to this potentially life threatening emerging zoonotic disease. The molecular mechanisms underlying the pathophysiology and intra-erythrocytic development of these parasites are poorly understood. This impedes concerted efforts aimed at the discovery of novel anti-babesiacidal agents. By applying sensitive cell biological and molecular functional genomics tools, we describe the intra-erythrocytic development cycle of B. divergens parasites from immature, mono-nucleated ring forms to bi-nucleated paired piriforms and ultimately multi-nucleated tetrads that characterizes zoonotic Babesia spp. This is further correlated for the first time to nuclear content increases during intra-erythrocytic development progression, providing insight into the part of the life cycle that occurs during human infection. High-content temporal evaluation elucidated the contribution of the different stages to life cycle progression. Moreover, molecular descriptors indicate that B. divergens parasites employ physiological adaptation to in vitro cultivation. Additionally, differential expression is observed as the parasite equilibrates its developmental stages during its life cycle. Together, this information provides the first temporal evaluation of the functional transcriptome of B. divergens parasites, information that could be useful in identifying biological processes essential to parasite survival for future anti-babesiacidal discoveries.

Herring and chicken/pork meals lead to differences in plasma levels of TCA intermediates and arginine metabolites in overweight and obese men and women

DEFF Research Database (Denmark)

Vincent, Andrew; Savolainen, Otto I; Sen, Partho

2017-01-01

citrate, fumarate, isocitrate, glycolate, oxalate, agmatine and methyhistidine and increased asparagine, ornithine, glutamine and the hexosamine glucosamine. Modelling found that the tricarboxylic acid cycle, glyoxylate, and argininemetabolism were affected by the intervention. The effect on arginine...... metabolism was supported by an increase in blood nitric oxide in males on the herring diet. Conclusion: The results suggest that eating herring instead of chicken and lean pork leads to important metabolic effects, particularly on energy and amino acid metabolism. Our findings support the hypothesis...... that there are metabolic effects of herring intake unrelated to the long chain n-3 polyunsaturated fatty acid content....

Study of the G2/M cell cycle checkpoint in irradiated mammary epithelial cells overexpressing Cul-4A gene

International Nuclear Information System (INIS)

Gupta, Anu; Yang, L.-X.; Chen, L.-C.

2002-01-01

Purpose: Members of the cullin gene family are known to be involved in cell cycle control. One of the cullin genes, Cul-4A, is amplified and overexpressed in breast cancer cells. This study investigates the effect of Cul-4A overexpression upon G2/M cell cycle checkpoint after DNA damage induced by either ionizing or nonionizing radiation. Methods and Materials: The normal mammary epithelial cell line MCF10A was stably transfected with full-length Cul-4A cDNA. Independent clones of MCF10A cells that overexpress Cul-4A proteins were selected and treated with either 8 Gy of ionizing radiation or 7 J/M 2 of UV radiation. The profile of cell cycle progression and the accumulation of several cell cycle proteins were analyzed. Results: We found that overexpression of Cul-4A in MCF10A cells abrogated the G2/M cell cycle checkpoint in response to DNA damage induced by ionizing irradiation, but not to DNA damage induced by nonionizing radiation. Analysis of cell cycle proteins showed that after ionizing irradiation, p53 accumulated in the mock-transfected MCF10A cells, but not in the Cul-4A transfectants. Conclusion: Our results suggest a role for Cul-4A in tumorigenesis and/or tumor progression, possibly through disruption of cell cycle control

Progress report 2011-2013 - Brazilian Energy and Nuclear Research Institute - IPEN

International Nuclear Information System (INIS)

2014-01-01

This progress report presents the results of the R&D center of IPEN in accordance with the main programs: Lasers Technology, Applications of Ionizing Radiations, Biotechnology, Renewable Energies, Radiopharmacy, Nuclear Science and Technology, Environmental Science and Technology, Nuclear Reactors and Fuel Cycle, Materials and Nanotechnology, Nuclear Safety, Education, Brazilian Multipurpose Reactor and Scientific and Technical Production

Progress report 2008-2010 - Brazilian Energy and Nuclear Research Institute - IPEN

International Nuclear Information System (INIS)

2011-01-01

This progress report presents the results of the R and D center of IPEN in the areas of: Lasers Technology; Renewable Energies; Nuclear Reactors and Fuel Cycle; Applications of Ionizing Radiations; Nuclear Science and Technology; Materials and Nanotechnology; Environmental Science and Technology; Radiopharmacy; Nuclear Safety; and Education. Also presents the Technical and Scientific Production od the center

Review of supercritical CO{sub 2} power cycle technology and current status of research and development

Energy Technology Data Exchange (ETDEWEB)

Ahn, Yoon Han; Bae, Seong Jun; Kim, Min Seok; Cho, Seong Kuk; Baik, Seung Joon; Lee, Jeong Ik [Dept. of Nuclear and Quantum Engineering, Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of); Cha, Jae Eun [Fast Reactor Technology Development Division, Korean Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2015-10-15

The supercritical CO{sub 2} (S-CO{sub 2}) Brayton cycle has recently been gaining a lot of attention for application to next generation nuclear reactors. The advantages of the S-CO-2 cycle are high efficiency in the mild turbine inlet temperature region and a small physical footprint with a simple layout, compact turbomachinery, and heat exchangers. Several heat sources including nuclear, fossil fuel, waste heat, and renewable heat sources such as solar thermal or fuel cells are potential application areas of the S-CO-2 cycle. In this paper, the current development progress of the S-CO-2 cycle is introduced. Moreover, a quick comparison of various S-CO{sub 2} layouts is presented in terms of cycle performance.

[Morphology, biology and life-cycle of Plasmodium parasites].

Science.gov (United States)

Hommel, Marcel

2007-10-01

Laveran first discovered that an infectious agent was responsible for malaria by using a simple microscope, without the assistance of specific stains. Our knowledge of the Plasmodium life cycle and cellular biology has progressed with each technological advance, from Romanovsky staining and histology to electron microscopy, immunocytochemistry, molecular methods and modern imaging techniques. The use of bird, primate and rodent models also made a major contribution, notably in the development of antimalarial drugs that are still in use today.

Development and application of basis database for materials life cycle assessment in china

Science.gov (United States)

Li, Xiaoqing; Gong, Xianzheng; Liu, Yu

2017-03-01

As the data intensive method, high quality environmental burden data is an important premise of carrying out materials life cycle assessment (MLCA), and the reliability of data directly influences the reliability of the assessment results and its application performance. Therefore, building Chinese MLCA database is the basic data needs and technical supports for carrying out and improving LCA practice. Firstly, some new progress on database which related to materials life cycle assessment research and development are introduced. Secondly, according to requirement of ISO 14040 series standards, the database framework and main datasets of the materials life cycle assessment are studied. Thirdly, MLCA data platform based on big data is developed. Finally, the future research works were proposed and discussed.

Heterocyclic organobismuth (III) compounds containing an eight-membered ring: Inhibitory effects on cell cycle progression.

Science.gov (United States)

Iuchi, Katsuya; Yagura, Tatsuo

2018-03-21

We previously showed that heterocyclic organobismuth compounds have excellent antimicrobial and antitumor potential. These compounds structurally consist of either six- or eight-membered rings. Previous research has shown that bi-chlorodibenzo[c,f][1,5]thiabismocine (Compound 3), an eight-membered ring, induced G 2 /M arrest via inhibition of tubulin polymerization in HeLa cells. Additionally, N-tert-butyl-bi-chlorodi-benzo[c,f][1,5]azabismocine (Compound 1), another eight-membered ring, exhibited higher cytotoxicity than Compound 3 against several cancer cell lines, including HeLa and K562. Finally, bi-chlorophenothiabismin-S,S-dioxide (Compound 5), a six-membered ring, exhibited lower antitumor activity than eight-membered ring compounds. In this study, we investigated the antimitotic activity of Compounds 1 and 5 in HeLa cells. At low concentrations, (0.1 and 0.25 μM), Compound 1 inhibited cell growth and arrested the cell cycle in mitosis. However, 0.5 μM Compound 1 exhibited no antimitotic activity. Conversely, Compound 5 weakly inhibited cell growth and did not markedly arrest the cell cycle. Flow cytometry showed that Compound 1 arrested the cell cycle at G 2 /M, resulting in apoptosis. Compound 1 inhibited tubulin polymerization as revealed by a cell-free assay, and both Compounds 1 and 3 inhibited microtubule spindle formation and chromosome alignment during prometaphase. These results suggest that eight-membered ring-containing organobismuth compounds can induce mitotic arrest by perturbing spindle dynamics. Copyright © 2018. Published by Elsevier Ltd.

Estimating the power efficiency of the thermal power plant modernization by using combined-cycle technologies

International Nuclear Information System (INIS)

Hovhannisyan, L.S.; Harutyunyan, N.R.

2013-01-01

The power efficiency of the thermal power plant (TPP) modernization by using combined-cycle technologies is introduced. It is shown that it is possible to achieve the greatest decrease in the specific fuel consumption at modernizing the TPP at the expense of introducing progressive 'know-how' of the electric power generation: for TPP on gas, it is combined-cycle, gas-turbine superstructures of steam-power plants and gas-turbines with heat utilization

Opportunities for sub-laser-cycle spectroscopy in condensed phase

International Nuclear Information System (INIS)

Ivanov, Misha; Smirnova, Olga

2013-01-01

Highlights: ► We discuss how sub-cycle attosecond spectroscopy can be extended from gas to condensed phase. ► We show that attosecond streaking measurements can be applied to bound electrons. ► We discuss time-resolving the formation of band structure in laser fields. - Abstract: To a large extent, progress of attosecond spectroscopy in the gas phase has been driven by designing approaches where time-resolution is not limited by the pulse duration. Instead, the time resolution comes from exploiting the sensitivity of electronic response to the oscillations of the electric field in the laser pulse and attosecond control over these oscillations. This paper discusses perspectives and opportunities for transporting the ideas of sub-cycle spectroscopy from gas to condensed phase

Effect of dihydroartemisinin on the cell cycle progress of irradiated human cervical cancer cell line and its mechanism

International Nuclear Information System (INIS)

Chen Xialin; Ji Rong; Cao Jianping; Zhu Wei; Fan Sanjun; Wang Jianfang; Cao Jianping

2010-01-01

Objective: To observe the changes of cell cycle on cancer cells after dihydroartemisinin and X-ray irradiation. Methods: Human HeLa cells of cervical cancer with p53 mutation was used and human SiHa cells of cervical cancer with wild p53 was used as control. Flow cytometry was used to detect the effect of dihydroartemisinin (20 and 100 μmol/L) and irradiation (6 Gy)on cell cycle. Western blot was used to measure the levels of cell cycle protein. Results: G 2 arrest was observed in irradiated HeLa cells, which the proportion of cells in G 2 phase was increased from 14.45% to 73.58% after 6 Gy X-ray irradiation, but it was abrogated by dihydroartemisinin from 73. 58% to 48.31% in HeLa cells, and it had no change on the SiHa cells. The elevated Wee1 protein and the lowered Cyclin B1 protein were observed with the G 2 arrest severity. The expression of radiation-induced Wee1 protein was suppressed and the Cyclin B1 protein was increased after dihydroartemisinin treatment, which was in accordance with the abrogation of radiation-induced G 2 delay. Conclusions: The main effect of irradiation on cell cycle of p53 mutated HeLa cells is G 2 arrest. Dihydroartemisinin could abrogate it, which is associated with the changes of Wee1 protein and Cyclin B1 protein. In Siha cells, the main effect of irradiation on cell cycle is G 1 arrest, and dihydroartemisinin has no effect on it. (authors)

HNRNPLL stabilizes mRNAs for DNA replication proteins and promotes cell cycle progression in colorectal cancer cells.

Science.gov (United States)

Sakuma, Keiichiro; Sasaki, Eiichi; Kimura, Kenya; Komori, Koji; Shimizu, Yasuhiro; Yatabe, Yasushi; Aoki, Masahiro

2018-06-05

HNRNPLL (heterogeneous nuclear ribonucleoprotein L-like), an RNA-binding protein that regulates alternative splicing of pre-mRNAs, has been shown to regulate differentiation of lymphocytes, as well as metastasis of colorectal cancer cells. Here we show that HNRNPLL promotes cell cycle progression and hence proliferation of colorectal cancer cells. Functional annotation analysis of those genes whose expression levels were changed by three-fold or more in RNA sequencing analysis between SW480 cells overexpressing HNRNPLL and those knocked down for HNRNPLL revealed enrichment of DNA replication-related genes by HNRNPLL overexpression. Among 13 genes detected in the DNA replication pathway, PCNA, RFC3, and FEN1 showed reproducible upregulation by HNRNPLL overexpression both at mRNA and protein levels in SW480 and HT29 cells. Importantly, knockdown of any of these genes alone suppressed the proliferation promoting effect induced by HNRNPLL overexpression. RNA-immunoprecipitation assay presented a binding of FLAG-tagged HNRNPLL to mRNA of these genes, and HNRNPLL overexpression significantly suppressed the downregulation of these genes during 12 hours of actinomycin D treatment, suggesting a role of HNRNPLL in mRNA stability. Finally, analysis of a public RNA sequencing dataset of clinical samples suggested a link between overexpression of HNRNPLL and that of PCNA, RFC3, and FEN1. This link was further supported by immunohistochemistry of colorectal cancer clinical samples, whereas expression of CDKN1A, which is known to inhibit the cooperative function of PCNA, RFC3, and FEN1, was negatively associated with HNRNPLL expression. These results indicate that HNRNPLL stabilizes mRNAs encoding regulators of DNA replication and promotes colorectal cancer cell proliferation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Bipolar mood cycles and lunar tidal cycles.

Science.gov (United States)

Wehr, T A

2018-04-01

In 17 patients with rapid cycling bipolar disorder, time-series analyses detected synchronies between mood cycles and three lunar cycles that modulate the amplitude of the moon's semi-diurnal gravimetric tides: the 14.8-day spring-neap cycle, the 13.7-day declination cycle and the 206-day cycle of perigee-syzygies ('supermoons'). The analyses also revealed shifts among 1:2, 1:3, 2:3 and other modes of coupling of mood cycles to the two bi-weekly lunar cycles. These shifts appear to be responses to the conflicting demands of the mood cycles' being entrained simultaneously to two different bi-weekly lunar cycles with slightly different periods. Measurements of circadian rhythms in body temperature suggest a biological mechanism through which transits of one of the moon's semi-diurnal gravimetric tides might have driven the patients' bipolar cycles, by periodically entraining the circadian pacemaker to its 24.84-h rhythm and altering the pacemaker's phase-relationship to sleep in a manner that is known to cause switches from depression to mania.

Burnup effect on nuclear fuel cycle cost using an equilibrium model

International Nuclear Information System (INIS)

Youn, S. R.; Kim, S. K.; Ko, W. I.

2014-01-01

The degree of fuel burnup is an important technical parameter to the nuclear fuel cycle, being sensitive and progressive to reduce the total volume of process flow materials and eventually cut the nuclear fuel cycle costs. This paper performed the sensitivity analysis of the total nuclear fuel cycle costs to changes in the technical parameter by varying the degree of burnups in each of the three nuclear fuel cycles using an equilibrium model. Important as burnup does, burnup effect was used among the cost drivers of fuel cycle, as the technical parameter. The fuel cycle options analyzed in this paper are three different fuel cycle options as follows: PWR-Once Through Cycle(PWR-OT), PWR-MOX Recycle, Pyro-SFR Recycle. These fuel cycles are most likely to be adopted in the foreseeable future. As a result of the sensitivity analysis on burnup effect of each three different nuclear fuel cycle costs, PWR-MOX turned out to be the most influenced by burnup changes. Next to PWR-MOX cycle, in the order of Pyro-SFR and PWR-OT cycle turned out to be influenced by the degree of burnup. In conclusion, the degree of burnup in the three nuclear fuel cycles can act as the controlling driver of nuclear fuel cycle costs due to a reduction in the volume of spent fuel leading better availability and capacity factors. However, the equilibrium model used in this paper has a limit that time-dependent material flow and cost calculation is impossible. Hence, comparative analysis of the results calculated by dynamic model hereafter and the calculation results using an equilibrium model should be proceed. Moving forward to the foreseeable future with increasing burnups, further studies regarding alternative material of high corrosion resistance fuel cladding for the overall

Depth of dormancy in tomato seeds is related to the progression of the cell cycle prior to its induction

NARCIS (Netherlands)

Castro, de R.D.; Lammeren, van A.A.M.; Groot, S.P.C.; Bino, R.J.; Hilhorst, H.W.M.

2001-01-01

Cell cycle activities are initiated following imbibition of non-dormant seeds. However, it is not known whether cell cycle related events other than DNA replication also remain suppressed in imbibed dormant seeds. The objective of this study was to demonstrate that the transitions between the

Biomechanical spinal growth modulation and progressive adolescent scoliosis – a test of the 'vicious cycle' pathogenetic hypothesis: Summary of an electronic focus group debate of the IBSE

Directory of Open Access Journals (Sweden)

Burwell R Geoffrey

2006-10-01

Full Text Available Abstract There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS. As part of its mission to widen understanding of scoliosis etiology, the International Federated Body on Scoliosis Etiology (IBSE introduced the electronic focus group (EFG as a means of increasing debate on knowledge of important topics. This has been designated as an on-line Delphi discussion. The text for this debate was written by Dr Ian A Stokes. It evaluates the hypothesis that in progressive scoliosis vertebral body wedging during adolescent growth results from asymmetric muscular loading in a "vicious cycle" (vicious cycle hypothesis of pathogenesis by affecting vertebral body growth plates (endplate physes. A frontal plane mathematical simulation tested whether the calculated loading asymmetry created by muscles in a scoliotic spine could explain the observed rate of scoliosis increase by measuring the vertebral growth modulation by altered compression. The model deals only with vertebral (not disc wedging. It assumes that a pre-existing scoliosis curve initiates the mechanically-modulated alteration of vertebral body growth that in turn causes worsening of the scoliosis, while everything else is anatomically and physiologically 'normal' The results provide quantitative data consistent with the vicious cycle hypothesis. Dr Stokes' biomechanical research engenders controversy. A new speculative concept is proposed of vertebral symphyseal dysplasia with implications for Dr Stokes' research and the etiology of AIS. What is not controversial is the need to test this hypothesis using additional factors in his current model and in three-dimensional quantitative models that incorporate intervertebral discs and simulate thoracic as well as lumbar scoliosis. The growth modulation process in the vertebral body can be viewed as one type of the biologic phenomenon of mechanotransduction. In certain connective tissues this involves the

PSA response to cabazitaxel is associated with improved progression-free survival in metastatic castration-resistant prostate cancer: the non-interventional QoLiTime study.

Science.gov (United States)

Hammerer, Peter; Al-Batran, Salah-Eddin; Windemuth-Kieselbach, Christine; Keller, Martin; Hofheinz, Ralf-Dieter

2018-03-01

To evaluate the association between prostate-specific antigen (PSA) response and progression-free and overall survival in men with metastatic castration-resistant prostate cancer (mCRPC) treated with cabazitaxel. Men with mCRPC receiving cabazitaxel (25 mg/m 2 , every 3 weeks) plus oral prednis(ol)one (10 mg/day) were enrolled in the non-interventional, prospective QoLiTime study. Main outcome measures were progression-free survival and overall survival, in all patients and in those who showed a ≥ 50 or a ≥ 30% decrease in PSA relative to baseline after four cycles of cabazitaxel, as well as quality-of-life parameters. Of the 527 men (median age 72 years), 266 received ≥ 4 cycles of cabazitaxel and had PSA response data. After four cycles, 34.6% of men achieved a PSA decrease ≥ 50% and 49.6% a decrease ≥ 30%. Median progression-free survival was 7.7 (95% CI 6.2, 9.5) months, and overall survival was 19.5 (95% CI 16.0, 30.9) months, corresponding to 1-year event rates of 39.4 and 78.8%, respectively. Median progression-free survival was longer in PSA responders versus non-responders (15.7 vs 5.5 months at 50% cut-off; 15.7 vs 5.3 months for 30% cut-off; both P PSA response after four cycles of cabazitaxel is associated with improved progression-free survival in men with mCRPC treated with cabazitaxel plus prednis(ol)one.

WaterNet: The NASA Water Cycle Solutions Network

Science.gov (United States)

Houser, P. R.; Belvedere, D. R.; Pozzi, W. H.; Imam, B.; Schiffer, R.; Lawford, R.; Schlosser, C. A.; Gupta, H.; Welty, C.; Vorosmarty, C.; Matthews, D.

2007-12-01

Water is essential to life and directly impacts and constrains society's welfare, progress, and sustainable growth, and is continuously being transformed by climate change, erosion, pollution, and engineering practices. The water cycle is a critical resource for industry, agriculture, natural ecosystems, fisheries, aquaculture, hydroelectric power, recreation, and water supply, and is central to drought, flood, transportation-aviation, and disease hazards. It is therefore a national priority to use advancements in scientific observations and knowledge to develop solutions to the water challenges faced by society. NASA's unique role is to use its view from space to improve water and energy cycle monitoring and prediction. NASA has collected substantial water cycle information and knowledge that must be transitioned to develop solutions for all twelve National Priority Application (NPA) areas. NASA cannot achieve this goal alone -it must establish collaborations and interoperability with existing networks and nodes of research organizations, operational agencies, science communities, and private industry. Therefore, WaterNet: The NASA Water Cycle Solutions Network goal is to improve and optimize the sustained ability of water cycle researchers, stakeholders, organizations and networks to interact, identify, harness, and extend NASA research results to augment decision support tools and meet national needs. WaterNet is a catalyst for discovery and sharing of creative solutions to water problems. It serves as a creative, discovery process that is the entry-path for a research-to-solutions systems engineering NASA framework, with the end result to ultimately improve decision support.

Capsaicin induces cell cycle arrest and apoptosis in human KB cancer cells.

Science.gov (United States)

Lin, Chia-Han; Lu, Wei-Cheng; Wang, Che-Wei; Chan, Ya-Chi; Chen, Mu-Kuan

2013-02-25

Capsaicin, a pungent phytochemical in a variety of red peppers of the genus Capsicum, has shown an anti-proliferative effect on various human cancer cell lines. In contrast, capsaicin has also been considered to promote the growth of cancer cells. Thus, the effects of capsaicin on various cell types need to be explored. The anti-proliferative effects of capsaicin on human KB cancer cells are still unknown. Therefore, we examined the viability, cell cycle progression, and factors associated with apoptosis in KB cells treated with capsaicin. The cell proliferation/viability and cytotoxicity of KB cells exposed to capsaicin were determined by a sulforhodamine B colorimetric assay and trypan blue exclusion. Apoptosis was detected by Hoechst staining and confirmed by western blot analysis of poly-(ADP-ribose) polymerase cleavage. Cell cycle distribution and changes of the mitochondrial membrane potential were analyzed by flow cytometry. Furthermore, the expression of caspase 3, 8 and 9 was evaluated by immunoblotting. We found that treatment of KB cells with capsaicin significantly reduced cell proliferation/viability and induced cell death in a dose-dependent manner compared with that in the untreated control. Cell cycle analysis indicated that exposure of KB cells to capsaicin resulted in cell cycle arrest at G2/M phase. Capsaicin-induced growth inhibition of KB cells appeared to be associated with induction of apoptosis. Moreover, capsaicin induced disruption of the mitochondrial membrane potential as well as activation of caspase 9, 3 and poly-(ADP-ribose) polymerase in KB cells. Our data demonstrate that capsaicin modulates cell cycle progression and induces apoptosis in human KB cancer cells through mitochondrial membrane permeabilization and caspase activation. These observations suggest an anti-cancer activity of capsaicin.

Protein kinase C signaling and cell cycle regulation

Directory of Open Access Journals (Sweden)

Adrian R Black

2013-01-01

Full Text Available A link between T cell proliferation and the protein kinase C (PKC family of serine/threonine kinases has been recognized for about thirty years. However, despite the wealth of information on PKC-mediated control of T cell activation, understanding of the effects of PKCs on the cell cycle machinery in this cell type remains limited. Studies in other systems have revealed important cell cycle-specific effects of PKC signaling that can either positively or negatively impact proliferation. The outcome of PKC activation is highly context-dependent, with the precise cell cycle target(s and overall effects determined by the specific isozyme involved, the timing of PKC activation, the cell type, and the signaling environment. Although PKCs can regulate all stages of the cell cycle, they appear to predominantly affect G0/G1 and G2. PKCs can modulate multiple cell cycle regulatory molecules, including cyclins, cyclin-dependent kinases (cdks, cdk inhibitors and cdc25 phosphatases; however, evidence points to Cip/Kip cdk inhibitors and D-type cyclins as key mediators of PKC-regulated cell cycle-specific effects. Several PKC isozymes can target Cip/Kip proteins to control G0/G1→S and/or G2→M transit, while effects on D-type cyclins regulate entry into and progression through G1. Analysis of PKC signaling in T cells has largely focused on its roles in T cell activation; thus, observed cell cycle effects are mainly positive. A prominent role is emerging for PKCθ, with non-redundant functions of other isozymes also described. Additional evidence points to PKCδ as a negative regulator of the cell cycle in these cells. As in other cell types, context-dependent effects of individual isozymes have been noted in T cells, and Cip/Kip cdk inhibitors and D-type cyclins appear to be major PKC targets. Future studies are anticipated to take advantage of the similarities between these various systems to enhance understanding of PKC-mediated cell cycle regulation in

Emerging role of LRRK2 in human neural progenitor cell cycle progression, survival and differentiation

Directory of Open Access Journals (Sweden)

Meyer Anne K

2009-06-01

Full Text Available Abstract Despite a comprehensive mapping of the Parkinson's disease (PD-related mRNA and protein leucine-rich repeat kinase 2 (LRRK2 in the mammalian brain, its physiological function in healthy individuals remains enigmatic. Based on its structural features and kinase properties, LRRK2 may interact with other proteins involved in signalling pathways. Here, we show a widespread LRRK2 mRNA and/or protein expression in expanded or differentiated human mesencephalic neural progenitor cells (hmNPCs and in post-mortem substantia nigra PD patients. Using small interfering RNA duplexes targeting LRRK2 in hmNPCs following their differentiation into glia and neurons, we observed a reduced number of dopaminergic neurons due to apoptosis in LRRK2 knockdown samples. LRRK2-deficient hmNPCs exhibited elevated cell cycle- and cell death-related markers. In conclusion, a reduction of LRRK2 expression in hmNPCs severely impaired dopaminergic differentiation and/or survival of dopaminergic neurons most likely via preserving or reactivating the cell cycle.

International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO). 2011 Progress Report. Enhancing Global Nuclear Energy Sustainability

Energy Technology Data Exchange (ETDEWEB)

NONE

2012-05-15

When INPRO was established in 2000, some key characteristics and main objectives for the project were determined and remain basically unchanged to this day: to help ensure that nuclear energy is available to contribute to satisfying energy needs in the 21st century in a sustainable manner and to bring together technology holders, technology users and other stakeholders to consider jointly the national and international actions required to achieve desired innovations in nuclear reactors and fuel cycles. I wish to use the occasion of this INPRO Progress Report to review some of the key highlights of the past year and share with you my views and vision of INPRO's future. The ''Great East Japan Earthquake and Tsunami'' and the resulting accident at TEPCO's Fukushima Daiichi nuclear power plant occurred on 11 March 2011. In response to this accident and at the request of its Member States, the IAEA drafted an Action Plan which defines a programme of work o strengthen the global nuclear safety framework. The activities proposed in the Action Plan are meant to be implemented in the near term, to assess the safety of operating nuclear power plants n the light of lessons learned from the Fukushima Daiichi accident. The assessment covers both technical elements, specifically the design of nuclear power plants with regard to site specific extreme natural hazards, and institutional elements, such as the effectiveness of regulatory bodies, operating organizations and the international legal framework in regard to the implementation of IAEA Safety tandards and Conventions. The lessons learned in the medium and long terms will also be reflected n a periodic update of the design requirements for nuclear power plants, international safety tandards, regulations issued by national supervisory authorities, operational procedures, emergency planning and safety assessment methodologies. INPRO has a long term perspective and provides an assessment of the whole nuclear system. Ensuring

International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO). 2011 Progress Report. Enhancing Global Nuclear Energy Sustainability

International Nuclear Information System (INIS)

2012-05-01

When INPRO was established in 2000, some key characteristics and main objectives for the project were determined and remain basically unchanged to this day: to help ensure that nuclear energy is available to contribute to satisfying energy needs in the 21st century in a sustainable manner and to bring together technology holders, technology users and other stakeholders to consider jointly the national and international actions required to achieve desired innovations in nuclear reactors and fuel cycles. I wish to use the occasion of this INPRO Progress Report to review some of the key highlights of the past year and share with you my views and vision of INPRO's future. The ''Great East Japan Earthquake and Tsunami'' and the resulting accident at TEPCO's Fukushima Daiichi nuclear power plant occurred on 11 March 2011. In response to this accident and at the request of its Member States, the IAEA drafted an Action Plan which defines a programme of work o strengthen the global nuclear safety framework. The activities proposed in the Action Plan are meant to be implemented in the near term, to assess the safety of operating nuclear power plants n the light of lessons learned from the Fukushima Daiichi accident. The assessment covers both technical elements, specifically the design of nuclear power plants with regard to site specific extreme natural hazards, and institutional elements, such as the effectiveness of regulatory bodies, operating organizations and the international legal framework in regard to the implementation of IAEA Safety tandards and Conventions. The lessons learned in the medium and long terms will also be reflected n a periodic update of the design requirements for nuclear power plants, international safety tandards, regulations issued by national supervisory authorities, operational procedures, emergency planning and safety assessment methodologies. INPRO has a long term perspective and provides an assessment of the whole nuclear system. Ensuring

Cell cycle-tailored targeting of metastatic melanoma: Challenges and opportunities.

Science.gov (United States)

Haass, Nikolas K; Gabrielli, Brian

2017-07-01

The advent of targeted therapies of metastatic melanoma, such as MAPK pathway inhibitors and immune checkpoint antagonists, has turned dermato-oncology from the "bad guy" to the "poster child" in oncology. Current targeted therapies are effective, although here is a clear need to develop combination therapies to delay the onset of resistance. Many antimelanoma drugs impact on the cell cycle but are also dependent on certain cell cycle phases resulting in cell cycle phase-specific drug insensitivity. Here, we raise the question: Have combination trials been abandoned prematurely as ineffective possibly only because drug scheduling was not optimized? Firstly, if both drugs of a combination hit targets in the same melanoma cell, cell cycle-mediated drug insensitivity should be taken into account when planning combination therapies, timing of dosing schedules and choice of drug therapies in solid tumors. Secondly, if the combination is designed to target different tumor cell subpopulations of a heterogeneous tumor, one drug effective in a particular subpopulation should not negatively impact on the other drug targeting another subpopulation. In addition to the role of cell cycle stage and progression on standard chemotherapeutics and targeted drugs, we discuss the utilization of cell cycle checkpoint control defects to enhance chemotherapeutic responses or as targets themselves. We propose that cell cycle-tailored targeting of metastatic melanoma could further improve therapy outcomes and that our real-time cell cycle imaging 3D melanoma spheroid model could be utilized as a tool to measure and design drug scheduling approaches. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The sleep-wake cycle and Alzheimer's disease: what do we know?

Science.gov (United States)

Lim, Miranda M; Gerstner, Jason R; Holtzman, David M

2014-01-01

Sleep-wake disturbances are a highly prevalent and often disabling feature of Alzheimer's disease (AD). A cardinal feature of AD includes the formation of amyloid plaques, associated with the extracellular accumulation of the amyloid-β (Aβ) peptide. Evidence from animal and human studies suggests that Aβ pathology may disrupt the sleep-wake cycle, in that as Aβ accumulates, more sleep-wake fragmentation develops. Furthermore, recent research in animal and human studies suggests that the sleep-wake cycle itself may influence Alzheimer's disease onset and progression. Chronic sleep deprivation increases amyloid plaque deposition, and sleep extension results in fewer plaques in experimental models. In this review geared towards the practicing clinician, we discuss possible mechanisms underlying the reciprocal relationship between the sleep-wake cycle and AD pathology and behavior, and present current approaches to therapy for sleep disorders in AD.

AFCT/TFCT/ISFS Program. Technical progress report for the period April 1, 1978--June 30, 1978

Energy Technology Data Exchange (ETDEWEB)

Hill, O.F. (comp.)

1978-08-01

This is the tenth in a series of quarterly progress reports on studies performed for the Alternate Fuel Cycle Technologies/Thorium Fuel Cycle Technologies/International Spent Fuel Receipt and Storage (AFCT/TFCT/ISFS) Program. This program provides information needed by industry to close the back end of the power reactor fuel cycle. During the past quarter, studies were conducted in the following tasks: thorium resource price analyses; spent fuel receipt and storage; investigation of air cleaning processes for removing TBP from off-gas streams; study of iodine chemistry in process solutions, high-level waste treatment; electropolishing to decontaminate metallic waste from alternate and thorium converter fuel cycles; U.S. scale transport, dispersion and removal model comparison; safety criticality experiments; and criticality research in support of thorium fuel cycle.

Ethanol and Acetate Acting as Carbon/Energy Sources Negatively Affect Yeast Chronological Aging

Directory of Open Access Journals (Sweden)

Ivan Orlandi

2013-01-01

Full Text Available In Saccharomyces cerevisiae, the chronological lifespan (CLS is defined as the length of time that a population of nondividing cells can survive in stationary phase. In this phase, cells remain metabolically active, albeit at reduced levels, and responsive to environmental signals, thus simulating the postmitotic quiescent state of mammalian cells. Many studies on the main nutrient signaling pathways have uncovered the strong influence of growth conditions, including the composition of culture media, on CLS. In this context, two byproducts of yeast glucose fermentation, ethanol and acetic acid, have been proposed as extrinsic proaging factors. Here, we report that ethanol and acetic acid, at physiological levels released in the exhausted medium, both contribute to chronological aging. Moreover, this combined proaging effect is not due to a toxic environment created by their presence but is mainly mediated by the metabolic pathways required for their utilization as carbon/energy sources. In addition, measurements of key enzymatic activities of the glyoxylate cycle and gluconeogenesis, together with respiration assays performed in extreme calorie restriction, point to a long-term quiescent program favoured by glyoxylate/gluconeogenesis flux contrary to a proaging one based on the oxidative metabolism of ethanol/acetate via TCA and mitochondrial respiration.

Architecture and inherent robustness of a bacterial cell-cycle control system.

Science.gov (United States)

Shen, Xiling; Collier, Justine; Dill, David; Shapiro, Lucy; Horowitz, Mark; McAdams, Harley H

2008-08-12

A closed-loop control system drives progression of the coupled stalked and swarmer cell cycles of the bacterium Caulobacter crescentus in a near-mechanical step-like fashion. The cell-cycle control has a cyclical genetic circuit composed of four regulatory proteins with tight coupling to processive chromosome replication and cell division subsystems. We report a hybrid simulation of the coupled cell-cycle control system, including asymmetric cell division and responses to external starvation signals, that replicates mRNA and protein concentration patterns and is consistent with observed mutant phenotypes. An asynchronous sequential digital circuit model equivalent to the validated simulation model was created. Formal model-checking analysis of the digital circuit showed that the cell-cycle control is robust to intrinsic stochastic variations in reaction rates and nutrient supply, and that it reliably stops and restarts to accommodate nutrient starvation. Model checking also showed that mechanisms involving methylation-state changes in regulatory promoter regions during DNA replication increase the robustness of the cell-cycle control. The hybrid cell-cycle simulation implementation is inherently extensible and provides a promising approach for development of whole-cell behavioral models that can replicate the observed functionality of the cell and its responses to changing environmental conditions.

Use of micro gas chromatography in the fuel cycle of fusion reactors

International Nuclear Information System (INIS)

Laesser, R.; Gruenhagen, S.; Kawamura, Y.

2003-01-01

Various analytical techniques exist to determine the compositions of gases handled in the fuel cycle of future fusion machines. Gas chromatography was found to be the most appropriate method. The main disadvantages of conventional gas chromatography were the long retention times for the heavy hydrogen species of >30 min. Recent progress in the development of micro-gas chromatography has reduced these retention times to ∼3 min. The usefulness of micro-gas chromatography for the analysis of hydrogen and impurity gas mixtures in the fuel cycle of future fusion machines is presented and the advantages and drawbacks are discussed

CANDU fuel cycle options in Korea

International Nuclear Information System (INIS)

Boczar, P. G.; Fehrenbach, P. J.; Meneley, D. A.

1996-01-01

There are many reasons for countries embarking on a CANDU R program to start with the natural uranium fuel cycle. Simplicity of fuel design, ease of fabrication, and ready availability of natural uranium all help to localize the technology and to reduce reliance on foreign technology. Nonetheless, at some point, the incentives for using natural uranium fuel may be outweighed by the advantages of alternate fuel cycles. The excellent neutron economy, on-line refuelling, and simple fuel-bundle design provide an unsurpassed degree of fuel-cycle flexibility in CANDU reactors. The easiest first step in CANDU fuel-cycle evolution may be the use of slightly enriched uranium (SEU), including recovered uranium from reprocessed LWR spent fuel. Relatively low enrichment (up to 1.2%) will result in a two- to three-fold reduction in the quantity of spent fuel per unit energy production, reductions in fuel-cycle costs, and greater flexibility in the design of new reactors. The CANFLEX (CANDU FLEXible) fuel bundle would be the optimal fuel carrier. A country that has both CANDU and PWR reactors can exploit the natural synergism between these two reactor types to minimize overall waste production, and maximize energy derived from the fuel. This synergism can be exploited through several different fuel cycles. A high burnup CANDU MOX fuel design could be used to utilize plutonium from conventional reprocessing or more advanced reprocessing options (such as co-processing). DUPIC (Direct Use of Spent PWR Fuel In CANDU) represents a recycle option that has a higher degree of proliferation resistance than dose conventional reprocessing, since it uses only dry processes for converting spent PWR fuel into CANDU fuel, without separating the plutonium. Good progress is being made in the current KAERI, AECL, and U. S. Department of State program in demonstrating the technical feasibility of DUPIC. In the longer term, CANDU reactors offer even more dramatic synergistic fuel cycles with PWR or

Integrated operation of the photorespiratory cycle and cytosolic metabolism in the modulation of primary nitrogen assimilation and export of organic N-transport compounds from leaves: a hypothesis.

Science.gov (United States)

Misra, Jitendra B

2014-02-15

Photorespiration is generally considered to be an essentially dissipative process, although it performs some protective and essential functions. A theoretical appraisal indicates that the loss of freshly assimilated CO2 due to photorespiration in well-watered plants may not be as high as generally believed. Even under moderately adverse conditions, these losses may not exceed 10%. The photorespiratory metabolism of the source leaves of well-watered and well-nourished crop plants ought to be different from that of other leaves because the fluxes of the export of both carbohydrates and organic N-transport compounds in source leaves is quite high. With a heuristic approach that involved the dovetailing of certain metabolic steps with the photorespiratory cycle (PR-cycle), a novel network is proposed to operate in the source-leaves of well-watered and well-nourished plants. This network allows for the diversion of metabolites from their cyclic-routes in sizeable quantities. With the removal of considerable quantities of glycine and serine from the cyclic route, the number of RuBP oxygenation events would be several times those of the formation of hydroxypyruvate. Thus, to an extreme extent, photorespiratory metabolism would become open-ended and involve much less futile recycling of glycine and serine. Conversion of glyoxylate to glycine has been proposed to be a crucial step in the determination of the relative rates of the futile (cyclic) and anabolic (open-ended) routes. Thus, in the source leaves of well-watered and well-nourished plants, the importance of the cyclic route is limited to the salvaging of photorespiratory intermediates for the regeneration of RuBP. The proposed network is resilient enough to coordinate the rates of the assimilation of carbon and nitrogen in accordance with the moisture and N-fertility statuses of the soil. Copyright © 2013 Elsevier GmbH. All rights reserved.

Cycling with an amputation: A systematic review.

Science.gov (United States)

Dyer, Bryce

2016-10-01

Cycling with any form of limb amputation has progressed from an activity of leisure or rehabilitation to elite level competition as part of the Paralympic Games programme. While it is often proposed that research into sport with an amputation can be extremely limited, this study intended to identify the volume, type and historical strategy in this area. This study comprises a documented systematic literature review of cycling undertaken with any form of limb amputation. This study used four online search engines to identify relevant peer-reviewed literature. These included SPORTDiscus, CINAHL, Scopus and MEDLINE. Google Scholar was also used as a secondary source. The initial results were then subjected to a set of pre-defined inclusion criteria. The resulting publications were then analysed for content and thematic commonality. The review identified 20 articles which met pre-defined inclusion criteria. The identified peer-reviewed publications were dated from the period 2004 to 2014. Three clear themes emerged from the historical research. There was both a paucity of peer-reviewed literature with respect to cycling with an amputation and the design of adaptive or assistive technology to replace limb loss. However, publications have been rising substantially over the last 5 years. This review study established the historical strategy and content of cycling with an amputation and identified the existing research themes. This will assist in summarising the current level of knowledge and help signpost such work in the future. © The International Society for Prosthetics and Orthotics 2015.

DNA Copy-Number Control through Inhibition of Replication Fork Progression

Directory of Open Access Journals (Sweden)

Jared T. Nordman

2014-11-01

Full Text Available Proper control of DNA replication is essential to ensure faithful transmission of genetic material and prevent chromosomal aberrations that can drive cancer progression and developmental disorders. DNA replication is regulated primarily at the level of initiation and is under strict cell-cycle regulation. Importantly, DNA replication is highly influenced by developmental cues. In Drosophila, specific regions of the genome are repressed for DNA replication during differentiation by the SNF2 domain-containing protein SUUR through an unknown mechanism. We demonstrate that SUUR is recruited to active replication forks and mediates the repression of DNA replication by directly inhibiting replication fork progression instead of functioning as a replication fork barrier. Mass spectrometry identification of SUUR-associated proteins identified the replicative helicase member CDC45 as a SUUR-associated protein, supporting a role for SUUR directly at replication forks. Our results reveal that control of eukaryotic DNA copy number can occur through the inhibition of replication fork progression.

Cell cycle and aging, morphogenesis, and response to stimuli genes are individualized biomarkers of glioblastoma progression and survival

Directory of Open Access Journals (Sweden)

Southey Bruce R

2011-06-01

Full Text Available Abstract Background Glioblastoma is a complex multifactorial disorder that has swift and devastating consequences. Few genes have been consistently identified as prognostic biomarkers of glioblastoma survival. The goal of this study was to identify general and clinical-dependent biomarker genes and biological processes of three complementary events: lifetime, overall and progression-free glioblastoma survival. Methods A novel analytical strategy was developed to identify general associations between the biomarkers and glioblastoma, and associations that depend on cohort groups, such as race, gender, and therapy. Gene network inference, cross-validation and functional analyses further supported the identified biomarkers. Results A total of 61, 47 and 60 gene expression profiles were significantly associated with lifetime, overall, and progression-free survival, respectively. The vast majority of these genes have been previously reported to be associated with glioblastoma (35, 24, and 35 genes, respectively or with other cancers (10, 19, and 15 genes, respectively and the rest (16, 4, and 10 genes, respectively are novel associations. Pik3r1, E2f3, Akr1c3, Csf1, Jag2, Plcg1, Rpl37a, Sod2, Topors, Hras, Mdm2, Camk2g, Fstl1, Il13ra1, Mtap and Tp53 were associated with multiple survival events. Most genes (from 90 to 96% were associated with survival in a general or cohort-independent manner and thus the same trend is observed across all clinical levels studied. The most extreme associations between profiles and survival were observed for Syne1, Pdcd4, Ighg1, Tgfa, Pla2g7, and Paics. Several genes were found to have a cohort-dependent association with survival and these associations are the basis for individualized prognostic and gene-based therapies. C2, Egfr, Prkcb, Igf2bp3, and Gdf10 had gender-dependent associations; Sox10, Rps20, Rab31, and Vav3 had race-dependent associations; Chi3l1, Prkcb, Polr2d, and Apool had therapy-dependent associations

Gene disruption reveals a dispensable role for plasmepsin VII in the Plasmodium berghei life cycle.

Science.gov (United States)

Mastan, Babu S; Kumari, Anchala; Gupta, Dinesh; Mishra, Satish; Kumar, Kota Arun

2014-06-01

Plasmepsins (PM), aspartic proteases of Plasmodium, comprises a family of ten proteins that perform critical functions in Plasmodium life cycle. Except VII and VIII, functions of the remaining plasmepsin members have been well characterized. Here, we have generated a mutant parasite lacking PM VII in Plasmodium berghei using reverse genetics approach. Systematic comparison of growth kinetics and infection in both mosquito and vertebrate host revealed that PM VII depleted mutants exhibited no defects in development and progressed normally throughout the parasite life cycle. These studies suggest a dispensable role for PM VII in Plasmodium berghei life cycle. Copyright © 2014 Elsevier B.V. All rights reserved.

Analytical methods for fissionable material determinations in the nuclear fuel cycle. Progress report, October 1, 1976--September 30, 1977

International Nuclear Information System (INIS)

Waterbury, G.R.

1978-01-01

Development of dissolution techniques for difficult-to-dissolve nuclear materials, development of methods and automated instruments for plutonium and uranium determinations, preparation of plutonium-containing materials for the Safeguards Analytical Laboratory Evaluation (SALE) program, analysis of SALE uranium materials, preparation of certified reference material plutonium metal, measurement of longer plutonium isotope half-lives, and study of ion exchange behavior of elements in various media continued. Gas-solid reaction of carbonyl chloride with uranium-bearing materials at elevated temperature is superior to reaction with chlorine for uranium volatilization and separation. Neither reaction with a variety of nonaqueous solvents nor reaction with molten selenium oxide provides practical dissolution of refractory materials characteristic of nuclear fuel cycle materials. The LASL automated spectrophotometer has been used to determine 0.1-mg amounts without instrumental or procedural changes. A microgram-sensitive spectrophotometric method for uranium has been developed, and the automated spectrophotometer is being modified to its use. A controlled-potential coulometric method has been developed for selective determination of plutonium. An automated analyzer to use this method is being built. Uranium-plutonium mixed oxide powder, for SALE samples, has not remained stable during storage, but high-density pellets have. In a DOE interlaboratory program, the half-life of 239 Pu has been measured, experiments on 241 Pu half-life measurement are in progress, and 240 Pu half-life measurement is planned. Ion exchange distributions for over 50 elements have been measured to determine cation exchange in nitric acid and anion exchange in both hydrobromic and hydriodic acids

Analytical methods for fissionable material determinations in the nuclear fuel cycle. Progress report, October 1, 1976--September 30, 1977

Energy Technology Data Exchange (ETDEWEB)

Waterbury, G.R. (comp.)

1978-01-01

Development of dissolution techniques for difficult-to-dissolve nuclear materials, development of methods and automated instruments for plutonium and uranium determinations, preparation of plutonium-containing materials for the Safeguards Analytical Laboratory Evaluation (SALE) program, analysis of SALE uranium materials, preparation of certified reference material plutonium metal, measurement of longer plutonium isotope half-lives, and study of ion exchange behavior of elements in various media continued. Gas-solid reaction of carbonyl chloride with uranium-bearing materials at elevated temperature is superior to reaction with chlorine for uranium volatilization and separation. Neither reaction with a variety of nonaqueous solvents nor reaction with molten selenium oxide provides practical dissolution of refractory materials characteristic of nuclear fuel cycle materials. The LASL automated spectrophotometer has been used to determine 0.1-mg amounts without instrumental or procedural changes. A microgram-sensitive spectrophotometric method for uranium has been developed, and the automated spectrophotometer is being modified to its use. A controlled-potential coulometric method has been developed for selective determination of plutonium. An automated analyzer to use this method is being built. Uranium-plutonium mixed oxide powder, for SALE samples, has not remained stable during storage, but high-density pellets have. In a DOE interlaboratory program, the half-life of /sup 239/Pu has been measured, experiments on /sup 241/Pu half-life measurement are in progress, and /sup 240/Pu half-life measurement is planned. Ion exchange distributions for over 50 elements have been measured to determine cation exchange in nitric acid and anion exchange in both hydrobromic and hydriodic acids.

PARP-2 regulates cell cycle-related genes through histone deacetylation and methylation independently of poly(ADP-ribosyl)ation

International Nuclear Information System (INIS)

Liang, Ya-Chen; Hsu, Chiao-Yu; Yao, Ya-Li; Yang, Wen-Ming

2013-01-01

Highlights: ► PARP-2 acts as a transcription co-repressor independently of PARylation activity. ► PARP-2 recruits HDAC5, 7, and G9a and generates repressive chromatin. ► PARP-2 is recruited to the c-MYC promoter by DNA-binding factor YY1. ► PARP-2 represses cell cycle-related genes and alters cell cycle progression. -- Abstract: Poly(ADP-ribose) polymerase-2 (PARP-2) catalyzes poly(ADP-ribosyl)ation (PARylation) and regulates numerous nuclear processes, including transcription. Depletion of PARP-2 alters the activity of transcription factors and global gene expression. However, the molecular action of how PARP-2 controls the transcription of target promoters remains unclear. Here we report that PARP-2 possesses transcriptional repression activity independently of its enzymatic activity. PARP-2 interacts and recruits histone deacetylases HDAC5 and HDAC7, and histone methyltransferase G9a to the promoters of cell cycle-related genes, generating repressive chromatin signatures. Our findings propose a novel mechanism of PARP-2 in transcriptional regulation involving specific protein–protein interactions and highlight the importance of PARP-2 in the regulation of cell cycle progression

Assessment of thermochemical hydrogen production. Project 8994 mid-contract progress report, July 1--November 1, 1977. [Iron chloride and copper sulfate cycles

Energy Technology Data Exchange (ETDEWEB)

Dafler, J.R.; Foh, S.E.; Schreiber, J.D.

1977-12-01

We have completed the base-case (first-cut) flowsheet analysis for two thermochemical water-splitting cycles that have been under study at the Institute of Gas Technology: a four-step iron chloride cycle (denoted B-1) and a four-step copper sulfate cycle (denoted H-5). In the case of Cycle B-1, an energy balance has located the worst problem areas in the cycle, and flowsheet modifications have begun. Calculations of equilibrium effects due to the hydrolysis of ferrous chloride at pressures high enough to interface with projected hydrogen transmission systems will, apparently, necessitate higher temperature process heat input for this step. Higher pressure operation of some critical separation processes yields more favorable heat balances. For Cycle H-5, the unmodified (base-case) flowsheet indicates that reaction product separations will be relatively simple with respect to Cycle B-1. Work of Schuetz and others dealing with the electrolysis and thermodynamics of HBr/H/sub 2/O/SO/sub 2/ systems is being extensively reviewed. Work plans for this part of the contract are currently being reviewed.

Development of cell-cycle checkpoint therapy for solid tumors.

Science.gov (United States)

Tamura, Kenji

2015-12-01

Cellular proliferation is tightly controlled by several cell-cycle checkpoint proteins. In cancer, the genes encoding these proteins are often disrupted and cause unrestrained cancer growth. The proteins are over-expressed in many malignancies; thus, they are potential targets for anti-cancer therapies. These proteins include cyclin-dependent kinase, checkpoint kinase, WEE1 kinase, aurora kinase and polo-like kinase. Cyclin-dependent kinase inhibitors are the most advanced cell-cycle checkpoint therapeutics available. For instance, palbociclib (PD0332991) is a first-in-class, oral, highly selective inhibitor of CDK4/6 and, in combination with letrozole (Phase II; PALOMA-1) or with fulvestrant (Phase III; PALOMA-3), it has significantly prolonged progression-free survival, in patients with metastatic estrogen receptor-positive, HER2-negative breast cancer, in comparison with that observed in patients using letrozole, or fulvestrant alone, respectively. In this review, we provide an overview of the current compounds available for cell-cycle checkpoint protein-directed therapy for solid tumors. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Fluorine uptake into human enamel around fluoride-containing dental materials during cariogenic pH cycling

Energy Technology Data Exchange (ETDEWEB)

Komatsu, H. [Graduate School of Dental Medicine, Hokkaido University, Kita-13, Nishi-7, Kita-ku, Sapporo 060-8586 (Japan)], E-mail: kom@den.hokudai.ac.jp; Yamamoto, H. [Graduate School of Dentistry, Osaka University, 1-8 Yamada-Oka, Suita 565-0871 (Japan); Nomachi, M. [Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka 560-0043 (Japan); Yasuda, K. [The Wakasa wan Energy Research Center, 64-52-1 Hase, Tsuruga 914-0192 (Japan); Matsuda, Y.; Kinugawa, M.; Kijimura, T.; Sano, H. [Graduate School of Dental Medicine, Hokkaido University, Kita-13, Nishi-7, Kita-ku, Sapporo 060-8586 (Japan); Satou, T.; Oikawa, S.; Kamiya, T. [Advanced Radiation Technology, TARRI, JAEA, 1233 Watanuki-machi, Takasaki 370-1292 (Japan)

2009-06-15

Using PIGE (Proton Induced Gamma Emission) technique at TARRI (Takasaki Advanced Radiation Research Institute), Japan, we measured fluorine (F) uptake into the tooth enamel around two fluoride-containing materials during caries progression using pH cycling. Class V cavities in extracted human teeth were drilled and filled with fluoride-containing materials (i.e. 'Fuji IX' (FN) and 'UniFil flow with MEGA bond' (UF)) and a non-fluoride-containing material (i.e. 'SOLARE with MEGA bond' (SO)). Three 120 {mu}m longitudinal sections including the filling material were obtained from each tooth. In order to simulate daily acid attack occurring in the oral cavity, the pH cycling (pH 6.8-4.5) was carried out for 1, 3 and 5 weeks, separately. After pH cycling, the caries progression in all specimens was observed using transverse microradiography (TMR). The F and calcium distributions of the specimens were evaluated using PIGE and PIXE techniques. The F distribution of the specimens clearly showed the F uptake from FN into enamel adjacent to the filling material, while the F uptakes from UF and SO were not detected. For UF, the MEGA bond (non-fluoride-containing) between the tooth and UniFil flow interfered with the F absorption into the tooth. For FN, the amount of F uptake into the subsurface enamel increased during pH cycling. The amount of F uptake in 5-week pH cycling had significantly higher value compared to those in 1- and 3-week pH cycling. For UF and SO, there were no significant differences between the different durations of pH cycling. Among fluoride-containing materials, there were some differences in the F uptake with increased pH cycling, which could possibly lead to obtaining difference in clinical performance. The data obtained using PIGE and PIXE techniques were useful in understanding the benefit of fluorine by means of fluoride-containing material for preventing caries.

Fluorine uptake into human enamel around fluoride-containing dental materials during cariogenic pH cycling

International Nuclear Information System (INIS)

Komatsu, H.; Yamamoto, H.; Nomachi, M.; Yasuda, K.; Matsuda, Y.; Kinugawa, M.; Kijimura, T.; Sano, H.; Satou, T.; Oikawa, S.; Kamiya, T.

2009-01-01

Using PIGE (Proton Induced Gamma Emission) technique at TARRI (Takasaki Advanced Radiation Research Institute), Japan, we measured fluorine (F) uptake into the tooth enamel around two fluoride-containing materials during caries progression using pH cycling. Class V cavities in extracted human teeth were drilled and filled with fluoride-containing materials (i.e. 'Fuji IX' (FN) and 'UniFil flow with MEGA bond' (UF)) and a non-fluoride-containing material (i.e. 'SOLARE with MEGA bond' (SO)). Three 120 μm longitudinal sections including the filling material were obtained from each tooth. In order to simulate daily acid attack occurring in the oral cavity, the pH cycling (pH 6.8-4.5) was carried out for 1, 3 and 5 weeks, separately. After pH cycling, the caries progression in all specimens was observed using transverse microradiography (TMR). The F and calcium distributions of the specimens were evaluated using PIGE and PIXE techniques. The F distribution of the specimens clearly showed the F uptake from FN into enamel adjacent to the filling material, while the F uptakes from UF and SO were not detected. For UF, the MEGA bond (non-fluoride-containing) between the tooth and UniFil flow interfered with the F absorption into the tooth. For FN, the amount of F uptake into the subsurface enamel increased during pH cycling. The amount of F uptake in 5-week pH cycling had significantly higher value compared to those in 1- and 3-week pH cycling. For UF and SO, there were no significant differences between the different durations of pH cycling. Among fluoride-containing materials, there were some differences in the F uptake with increased pH cycling, which could possibly lead to obtaining difference in clinical performance. The data obtained using PIGE and PIXE techniques were useful in understanding the benefit of fluorine by means of fluoride-containing material for preventing caries.

Label-free cell-cycle analysis by high-throughput quantitative phase time-stretch imaging flow cytometry

Science.gov (United States)

Mok, Aaron T. Y.; Lee, Kelvin C. M.; Wong, Kenneth K. Y.; Tsia, Kevin K.

2018-02-01

Biophysical properties of cells could complement and correlate biochemical markers to characterize a multitude of cellular states. Changes in cell size, dry mass and subcellular morphology, for instance, are relevant to cell-cycle progression which is prevalently evaluated by DNA-targeted fluorescence measurements. Quantitative-phase microscopy (QPM) is among the effective biophysical phenotyping tools that can quantify cell sizes and sub-cellular dry mass density distribution of single cells at high spatial resolution. However, limited camera frame rate and thus imaging throughput makes QPM incompatible with high-throughput flow cytometry - a gold standard in multiparametric cell-based assay. Here we present a high-throughput approach for label-free analysis of cell cycle based on quantitative-phase time-stretch imaging flow cytometry at a throughput of > 10,000 cells/s. Our time-stretch QPM system enables sub-cellular resolution even at high speed, allowing us to extract a multitude (at least 24) of single-cell biophysical phenotypes (from both amplitude and phase images). Those phenotypes can be combined to track cell-cycle progression based on a t-distributed stochastic neighbor embedding (t-SNE) algorithm. Using multivariate analysis of variance (MANOVA) discriminant analysis, cell-cycle phases can also be predicted label-free with high accuracy at >90% in G1 and G2 phase, and >80% in S phase. We anticipate that high throughput label-free cell cycle characterization could open new approaches for large-scale single-cell analysis, bringing new mechanistic insights into complex biological processes including diseases pathogenesis.

MHD power generation research, development and engineering. Quarterly progress report, October-December 1979

Energy Technology Data Exchange (ETDEWEB)

None

1979-01-01

Progress is reported on the following tasks: characterization of coal for open-cycle MHD power generation systems; compressive creep and strength studies of MHD preheater materials; preparation of coals for utilization in direct coal-fired MHD generation; characterization of volatile matter in coal; MHD materials evaluation; operability of the Moderate Temperature Slag Flow Facility; slag-seed equilibria and separations related to the MHD system; thermionic emission of coal and electrode materials; MHD instrumentation, consolidated inversion simulator, and data acquisition; combined MHD-steam plant cycle analysis and control; and slag physical properties - electrical and thermal conductivity. (WHK)

Dendrimer-Based Selective Proteostasis-Inhibition Strategy to Control NSCLC Growth and Progression.

Directory of Open Access Journals (Sweden)

Kyla Walworth

Full Text Available Elevated valosin containing protein (VCP/p97 levels promote the progression of non-small cell lung carcinoma (NSCLC. Although many VCP inhibitors are available, most of these therapeutic compounds have low specificity for targeted tumor cell delivery. Hence, the primary aim of this study was to evaluate the in vitro efficacy of dendrimer-encapsulated potent VCP-inhibitor drug in controlling non-small cell lung carcinoma (NSCLC progression. The VCP inhibitor(s (either in their pure form or encapsulated in generation-4 PAMAM-dendrimer with hydroxyl surface were tested for their in vitro efficacy in modulating H1299 (NSCLC cells proliferation, migration, invasion, apoptosis and cell cycle progression. Our results show that VCP inhibition by DBeQ was significantly more potent than NMS-873 as evident by decreased cell proliferation (p<0.0001, MTT-assay and migration (p<0.05; scratch-assay, and increased apoptosis (p<0.05; caspase-3/7-assay as compared to untreated control cells. Next, we found that dendrimer-encapsulated DBeQ (DDNDBeQ treatment increased ubiquitinated-protein accumulation in soluble protein-fraction (immunoblotting of H1299 cells as compared to DDN-control, implying the effectiveness of DBeQ in proteostasis-inhibition. We verified by immunostaining that DDNDBeQ treatment increases accumulation of ubiquitinated-proteins that co-localizes with an ER-marker, KDEL. We observed that proteostasis-inhibition with DDNDBeQ, significantly decreased cell migration rate (scratch-assay and transwell-invasion as compared to the control-DDN treatment (p<0.05. Moreover, DDNDBeQ treatment showed a significant decrease in cell proliferation (p<0.01, MTT-assay and increased caspase-3/7 mediated apoptotic cell death (p<0.05 as compared to DDN-control. This was further verified by cell cycle analysis (propidium-iodide-staining that demonstrated significant cell cycle arrest in the G2/M-phase (p<0.001 by DDNDBeQ treatment as compared to control

Proliferation marker pKi-67 affects the cell cycle in a self-regulated manner.

Science.gov (United States)

Schmidt, Mirko H H; Broll, Rainer; Bruch, Hans-Peter; Duchrow, Michael

2002-01-01

The proliferation marker pKi-67 is commonly used in research and pathology to detect proliferating cells. In a previous work, we found the protein to be associated with regulators of the cell cycle, controlling S-phase progression, as well as entry into and exit from mitosis. Here we investigate whether pKi-67 has a regulative effect on the cell cycle itself. For that purpose we cloned four fragments of pKi-67, together representing nearly the whole protein, and an N-terminal pKi-67 antisense oligonucleotide into a tetracycline inducible gene expression system. The sense fragments were C-terminally modified by addition of either a nuclear localization sequence (NLS) or a STOP codon to address the impact of their intracellular distribution. FACS based cell cycle analysis revealed that expression of nearly all pKi-67 domains and the antisense oligonucleotide led to a decreased amount of cells in S-phase and an increased number of cells in G(2)/M- and G(1)-phase. Subsequent analysis of the endogenous pKi-67 mRNA and protein levels revealed that the constructs with the most significant impact on the cell cycle were able to silence pKi-67 transcription as well. We conclude from the data that pKi-67 influences progression of S-phase and mitosis in a self-regulated manner and, therefore, effects the cell cycle checkpoints within both phases. Furthermore, we found pKi-67 mediates an anti-apoptotic effect on the cell and we verified that this marker, although it is a potential ribosomal catalyst, is not expressed in differentiated tissues with a high transcriptional activity. Copyright 2002 Wiley-Liss, Inc.

Cancer and birth defects surveillance system for communities around the Savannah River Site. Annual progress report

Energy Technology Data Exchange (ETDEWEB)

Dunbar, J.B.

1994-05-01

The US DOE funded this grant to the Medical University of South Carolina for a cancer and birth defects registry for an initial three year period which was completed as of April 29, 1994. While this Technical Progress Report is prepared principally to document the activities of year 03, it also summarizes the accomplishments of the first two years in order to put into perspective the energy and progress of the program over the entire three year funding cycle.

Cancer and birth defects surveillance system for communities around the Savannah River Site. Annual progress report

International Nuclear Information System (INIS)

Dunbar, J.B.

1994-05-01

The US DOE funded this grant to the Medical University of South Carolina for a cancer and birth defects registry for an initial three year period which was completed as of April 29, 1994. While this Technical Progress Report is prepared principally to document the activities of year 03, it also summarizes the accomplishments of the first two years in order to put into perspective the energy and progress of the program over the entire three year funding cycle

The Concerted Action of Type 2 and Type 3 Deiodinases Regulates the Cell Cycle and Survival of Basal Cell Carcinoma Cells.

Science.gov (United States)

Miro, Caterina; Ambrosio, Raffaele; De Stefano, Maria Angela; Di Girolamo, Daniela; Di Cicco, Emery; Cicatiello, Annunziata Gaetana; Mancino, Giuseppina; Porcelli, Tommaso; Raia, Maddalena; Del Vecchio, Luigi; Salvatore, Domenico; Dentice, Monica

2017-04-01

Thyroid hormones (THs) mediate pleiotropic cellular processes involved in metabolism, cellular proliferation, and differentiation. The intracellular hormonal environment can be tailored by the type 1 and 2 deiodinase enzymes D2 and D3, which catalyze TH activation and inactivation respectively. In many cellular systems, THs exert well-documented stimulatory or inhibitory effects on cell proliferation; however, the molecular mechanisms by which they control rates of cell cycle progression have not yet been entirely clarified. We previously showed that D3 depletion or TH treatment influences the proliferation and survival of basal cell carcinoma (BCC) cells. Surprisingly, we also found that BCC cells express not only sustained levels of D3 but also robust levels of D2. The aim of the present study was to dissect the contribution of D2 to TH metabolism in the BCC context, and to identify the molecular changes associated with cell proliferation and survival induced by TH and mediated by D2 and D3. We used the CRISPR/Cas9 technology to genetically deplete D2 and D3 in BCC cells and studied the consequences of depletion on cell cycle progression and on cell death. Cell cycle progression was analyzed by fluorescence activated cell sorting analysis of synchronized cells, and the apoptosis rate by annexin V incorporation. Mechanistic investigations revealed that D2 inactivation accelerates cell cycle progression thereby enhancing the proportion of S-phase cells and cyclin D1 expression. Conversely, D3 mutagenesis drastically suppressed cell proliferation and enhanced apoptosis of BCC cells. Furthermore, the basal apoptotic rate was oppositely regulated in D2- and D3-depleted cells. Our results indicate that BCC cells constitute an example in which the TH signal is finely tuned by the concerted expression of opposite-acting deiodinases. The dual regulation of D2 and D3 expression plays a critical role in cell cycle progression and cell death by influencing cyclin D1-mediated

Thermochemical water-splitting cycle, bench-scale investigations and process engineering. Annual report, October 1, 1978-September 30, 1979

Energy Technology Data Exchange (ETDEWEB)

Caprioglio, G.; McCorkle, K.H.; Besenbruch, G.E.; Rode, J.S.

1980-03-01

A program to investigate thermochemical water splitting has been under way at General Atomic Company (GA) since October 1972. This document is an annual progress report of Department of Energy (DOE) sponsored process development work on the GA sulfur-iodine thermochemical water splitting cycle. The work consisted of laboratory bench-scale investigations, demonstration of the process in a closed-loop cycle demonstrator, and process engineering design studies. A bench-scale system, consisting of three subunits, has been designed to study the cycle under continuous flow conditions. The designs of subunit I, which models the main solution reaction and product separation, and subunit II, which models the concentration and decomposition of sulfuric acid, were presented in an earlier annual report. The design of subunit III, which models the purification and decomposition of hydrogen iodide, is given in this report. Progress on the installation and operation of subunits I and II is described. A closed-loop cycle demonstrator was installed and operated based on a DOE request. Operation of the GA sulfur-iodine cycle was demonstrated in this system under recycle conditions. The process engineering addresses the flowsheet design of a large-scale production process consisting of four chemical sections (I through IV) and one helium heat supply section (V). The completed designs for sections I through V are presented. The thermal efficiency of the process calculated from the present flowsheet is 47%.

IFR fuel cycle--pyroprocess development

International Nuclear Information System (INIS)

Laidler, J.J.; Miller, W.E.; Johnson, T.R.; Ackerman, J.P.; Battles, J.E.

1992-01-01

The Integral Fast Reactor (IFR) fuel cycle is based on the use of a metallic fuel alloy, with nominal composition U-2OPu-lOZr. In its present state of development, this fuel system offers excellent high-burnup capabilities. Test fuel has been carried to burnups in excess of 20 atom % in EBR-II irradiations, and to peak burnups over 15 atom % in FFTF. The metallic fuel possesses physical characteristics, in particular very high thermal conductivity, that facilitate a high degree of passive inherent safety in the IFR design. The fuel has been shown to provide very large margins to failure in overpower transient events. Rapid overpower transient tests carried out in the TREAT reactor have shown the capability to withstand up to 400% overpower conditions before failing. An operational transient test conducted in EBR-II at a power ramp rate of 0.1% per second reached its termination point of 130% of normal power without any fuel failures. The IFR metallic fuel also exhibits superior compatibility with the liquid sodium coolant. Equally as important as the performance advantages offered by the use of metallic fuel is the fact that this fuel system permits the use of an innovative reprocessing method, known as ''pyroprocessing,'' featuring fused-salt electrorefining of the spent fuel. Development of the IFR pyroprocess has been underway at the Argonne National Laboratory for over five years, and great progress has been made toward establishing a commercially-viable process. Pyroprocessing offers a simple, compact means for closure of the fuel cycle, with anticipated significant savings in fuel cycle costs

Glutamine-derived 2-hydroxyglutarate is associated with disease progression in plasma cell malignancies

Science.gov (United States)

Gonsalves, Wilson I.; Hitosugi, Taro; Ghosh, Toshi; Jevremovic, Dragan; Petterson, Xuan-Mai; Wellik, Linda; Kumar, Shaji K.; Nair, K. Sreekumaran

2018-01-01

The production of the oncometabolite 2-hydroxyglutarate (2-HG) has been associated with c-MYC overexpression. c-MYC also regulates glutamine metabolism and drives progression of asymptomatic precursor plasma cell (PC) malignancies to symptomatic multiple myeloma (MM). However, the presence of 2-HG and its clinical significance in PC malignancies is unknown. By performing 13C stable isotope resolved metabolomics (SIRM) using U[13C6]Glucose and U[13C5]Glutamine in human myeloma cell lines (HMCLs), we show that 2-HG is produced in clonal PCs and is derived predominantly from glutamine anaplerosis into the TCA cycle. Furthermore, the 13C SIRM studies in HMCLs also demonstrate that glutamine is preferentially utilized by the TCA cycle compared with glucose. Finally, measuring the levels of 2-HG in the BM supernatant and peripheral blood plasma from patients with precursor PC malignancies such as smoldering MM (SMM) demonstrates that relatively elevated levels of 2-HG are associated with higher levels of c-MYC expression in the BM clonal PCs and with a subsequent shorter time to progression (TTP) to MM. Thus, measuring 2-HG levels in BM supernatant or peripheral blood plasma of SMM patients offers potential early identification of those patients at high risk of progression to MM, who could benefit from early therapeutic intervention. PMID:29321378

Prognostic Utility of Cell Cycle Progression Score in Men With Prostate Cancer After Primary External Beam Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Freedland, Stephen J., E-mail: steve.freedland@duke.edu [Department of Surgery, Durham VA Medical Center, Durham, North Carolina (United States); Department of Surgery (Urology), Duke University School of Medicine, Durham, North Carolina (United States); Department of Pathology, Duke University School of Medicine, Durham, North Carolina (United States); Gerber, Leah [Department of Surgery, Durham VA Medical Center, Durham, North Carolina (United States); Department of Surgery (Urology), Duke University School of Medicine, Durham, North Carolina (United States); Department of Pathology, Duke University School of Medicine, Durham, North Carolina (United States); Reid, Julia; Welbourn, William; Tikishvili, Eliso; Park, Jimmy; Younus, Adib; Gutin, Alexander; Sangale, Zaina; Lanchbury, Jerry S. [Myriad Genetics, Inc, Salt Lake City, Utah (United States); Salama, Joseph K. [Department of Radiation Oncology, Durham VA Medical Center, Durham, North Carolina (United States); Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina (United States); Stone, Steven [Myriad Genetics, Inc, Salt Lake City, Utah (United States)

2013-08-01

Purpose: To evaluate the prognostic utility of the cell cycle progression (CCP) score, a RNA signature based on the average expression level of 31 CCP genes, for predicting biochemical recurrence (BCR) in men with prostate cancer treated with external beam radiation therapy (EBRT) as their primary curative therapy. Methods and Materials: The CCP score was derived retrospectively from diagnostic biopsy specimens of men diagnosed with prostate cancer from 1991 to 2006 (n=141). All patients were treated with definitive EBRT; approximately half of the cohort was African American. Outcome was time from EBRT to BCR using the Phoenix definition. Median follow-up for patients without BCR was 4.8 years. Association with outcome was evaluated by Cox proportional hazards survival analysis and likelihood ratio tests. Results: Of 141 patients, 19 (13%) had BCR. The median CCP score for patient samples was 0.12. In univariable analysis, CCP score significantly predicted BCR (P=.0017). The hazard ratio for BCR was 2.55 for 1-unit increase in CCP score (equivalent to a doubling of gene expression). In a multivariable analysis that included Gleason score, prostate-specific antigen, percent positive cores, and androgen deprivation therapy, the hazard ratio for CCP changed only marginally and remained significant (P=.034), indicating that CCP provides prognostic information that is not provided by standard clinical parameters. With 10-year censoring, the CCP score was associated with prostate cancer-specific mortality (P=.013). There was no evidence for interaction between CCP and any clinical variable, including ethnicity. Conclusions: Among men treated with EBRT, the CCP score significantly predicted outcome and provided greater prognostic information than was available with clinical parameters. If validated in a larger cohort, CCP score could identify high-risk men undergoing EBRT who may need more aggressive therapy.

Prognostic Utility of Cell Cycle Progression Score in Men With Prostate Cancer After Primary External Beam Radiation Therapy

International Nuclear Information System (INIS)

Freedland, Stephen J.; Gerber, Leah; Reid, Julia; Welbourn, William; Tikishvili, Eliso; Park, Jimmy; Younus, Adib; Gutin, Alexander; Sangale, Zaina; Lanchbury, Jerry S.; Salama, Joseph K.; Stone, Steven

2013-01-01

Purpose: To evaluate the prognostic utility of the cell cycle progression (CCP) score, a RNA signature based on the average expression level of 31 CCP genes, for predicting biochemical recurrence (BCR) in men with prostate cancer treated with external beam radiation therapy (EBRT) as their primary curative therapy. Methods and Materials: The CCP score was derived retrospectively from diagnostic biopsy specimens of men diagnosed with prostate cancer from 1991 to 2006 (n=141). All patients were treated with definitive EBRT; approximately half of the cohort was African American. Outcome was time from EBRT to BCR using the Phoenix definition. Median follow-up for patients without BCR was 4.8 years. Association with outcome was evaluated by Cox proportional hazards survival analysis and likelihood ratio tests. Results: Of 141 patients, 19 (13%) had BCR. The median CCP score for patient samples was 0.12. In univariable analysis, CCP score significantly predicted BCR (P=.0017). The hazard ratio for BCR was 2.55 for 1-unit increase in CCP score (equivalent to a doubling of gene expression). In a multivariable analysis that included Gleason score, prostate-specific antigen, percent positive cores, and androgen deprivation therapy, the hazard ratio for CCP changed only marginally and remained significant (P=.034), indicating that CCP provides prognostic information that is not provided by standard clinical parameters. With 10-year censoring, the CCP score was associated with prostate cancer-specific mortality (P=.013). There was no evidence for interaction between CCP and any clinical variable, including ethnicity. Conclusions: Among men treated with EBRT, the CCP score significantly predicted outcome and provided greater prognostic information than was available with clinical parameters. If validated in a larger cohort, CCP score could identify high-risk men undergoing EBRT who may need more aggressive therapy

Positive Feedback Keeps Duration of Mitosis Temporally Insulated from Upstream Cell-Cycle Events.

Science.gov (United States)

Araujo, Ana Rita; Gelens, Lendert; Sheriff, Rahuman S M; Santos, Silvia D M

2016-10-20

Cell division is characterized by a sequence of events by which a cell gives rise to two daughter cells. Quantitative measurements of cell-cycle dynamics in single cells showed that despite variability in G1-, S-, and G2 phases, duration of mitosis is short and remarkably constant. Surprisingly, there is no correlation between cell-cycle length and mitotic duration, suggesting that mitosis is temporally insulated from variability in earlier cell-cycle phases. By combining live cell imaging and computational modeling, we showed that positive feedback is the molecular mechanism underlying the temporal insulation of mitosis. Perturbing positive feedback gave rise to a sluggish, variable entry and progression through mitosis and uncoupled duration of mitosis from variability in cell cycle length. We show that positive feedback is important to keep mitosis short, constant, and temporally insulated and anticipate it might be a commonly used regulatory strategy to create modularity in other biological systems. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Alternative ORC bottoming cycles FOR combined cycle power plants

International Nuclear Information System (INIS)

Chacartegui, R.; Sanchez, D.; Munoz, J.M.; Sanchez, T.

2009-01-01

In this work, low temperature Organic Rankine Cycles are studied as bottoming cycle in medium and large scale combined cycle power plants. The analysis aims to show the interest of using these alternative cycles with high efficiency heavy duty gas turbines, for example recuperative gas turbines with lower gas turbine exhaust temperatures than in conventional combined cycle gas turbines. The following organic fluids have been considered: R113, R245, isobutene, toluene, cyclohexane and isopentane. Competitive results have been obtained for toluene and cyclohexane ORC combined cycles, with reasonably high global efficiencies. The paper is structured in four main parts. A review of combined cycle and ORC cycle technologies is presented, followed by a thermodynamic analysis of combined cycles with commercial gas turbines and ORC low temperature bottoming cycles. Then, a parametric optimization of an ORC combined cycle plant is performed in order to achieve a better integration between these two technologies. Finally, some economic considerations related to the use of ORC in combined cycles are discussed.

The Solar Wind Source Cycle: Relationship to Dynamo Behavior

Science.gov (United States)

Luhmann, J. G.; Li, Y.; Lee, C. O.; Jian, L. K.; Petrie, G. J. D.; Arge, C. N.

2017-12-01

Solar cycle trends of interest include the evolving properties of the solar wind, the heliospheric medium through which the Sun's plasmas and fields interact with Earth and the planets -including the evolution of CME/ICMEs enroute. Solar wind sources include the coronal holes-the open field regions that constantly evolve with solar magnetic fields as the cycle progresses, and the streamers between them. The recent cycle has been notably important in demonstrating that not all solar cycles are alike when it comes to contributions from these sources, including in the case of ecliptic solar wind. In particular, it has modified our appreciation of the low latitude coronal hole and streamer sources because of their relative prevalence. One way to understand the basic relationship between these source differences and what is happening inside the Sun and on its surface is to use observation-based models like the PFSS model to evaluate the evolution of the coronal field geometry. Although the accuracy of these models is compromised around solar maximum by lack of global surface field information and the sometimes non-potential evolution of the field related to more frequent and widespread emergence of active regions, they still approximate the character of the coronal field state. We use these models to compare the inferred recent cycle coronal holes and streamer belt sources of solar wind with past cycle counterparts. The results illustrate how (still) hemispherically asymmetric weak polar fields maintain a complex mix of low-to-mid latitude solar wind sources throughout the latest cycle, with a related marked asymmetry in the hemispheric distribution of the ecliptic wind sources. This is likely to be repeated until the polar field strength significantly increases relative to the fields at low latitudes, and the latter symmetrize.

Coupling TOR to the Cell Cycle by the Greatwall–Endosulfine–PP2A-B55 Pathway

Directory of Open Access Journals (Sweden)

Livia Pérez-Hidalgo

2017-08-01

Full Text Available Cell growth and division are two processes tightly coupled in proliferating cells. While Target of Rapamycin (TOR is the master regulator of growth, the cell cycle is dictated by the activity of the cyclin-dependent kinases (CDKs. A long-standing question in cell biology is how these processes may be connected. Recent work has highlighted that regulating the phosphatases that revert CDK phosphorylations is as important as regulating the CDKs for cell cycle progression. At mitosis, maintaining a low level of protein phosphatase 2A (PP2A-B55 activity is essential for CDK substrates to achieve the correct level of phosphorylation. The conserved Greatwall–Endosulfine pathway has been shown to be required for PP2A-B55 inhibition at mitosis in yeasts and multicellular organisms. Interestingly, in yeasts, the Greatwall–Endosulfine pathway is negatively regulated by TOR Complex 1 (TORC1. Moreover, Greatwall–Endosulfine activation upon TORC1 inhibition has been shown to regulate the progression of the cell cycle at different points: the G1 phase in budding yeast, the G2/M transition and the differentiation response in fission yeast, and the entry into quiescence in both budding and fission yeasts. In this review, we discuss the recent findings on how the Greatwall–Endosulfine pathway may provide a connection between cell growth and the cell cycle machinery.

Cycling infrastructure for reducing cycling injuries in cyclists.

Science.gov (United States)

Mulvaney, Caroline A; Smith, Sherie; Watson, Michael C; Parkin, John; Coupland, Carol; Miller, Philip; Kendrick, Denise; McClintock, Hugh

2015-12-10

Cycling is an attractive form of transport. It is beneficial to the individual as a form of physical activity that may fit more readily into an individual's daily routine, such as for cycling to work and to the shops, than other physical activities such as visiting a gym. Cycling is also beneficial to the wider community and the environment as a result of fewer motorised journeys. Cyclists are seen as vulnerable road users who are frequently in close proximity to larger and faster motorised vehicles. Cycling infrastructure aims to make cycling both more convenient and safer for cyclists. This review is needed to guide transport planning. To:1. evaluate the effects of different types of cycling infrastructure on reducing cycling injuries in cyclists, by type of infrastructure;2. evaluate the effects of cycling infrastructure on reducing the severity of cycling injuries in cyclists;3. evaluate the effects of cycling infrastructure on reducing cycling injuries in cyclists with respect to age, sex and social group. We ran the most recent search on 2nd March 2015. We searched the Cochrane Injuries Group Specialised Register, CENTRAL (The Cochrane Library), MEDLINE (OvidSP), Embase Classic + Embase(OvidSP), PubMed and 10 other databases. We searched websites, handsearched conference proceedings, screened reference lists of included studies and previously published reviews and contacted relevant organisations. We included randomised controlled trials, cluster randomised controlled trials, controlled before-after studies, and interrupted time series studies which evaluated the effect of cycling infrastructure (such as cycle lanes, tracks or paths, speed management, roundabout design) on cyclist injury or collision rates. Studies had to include a comparator, that is, either no infrastructure or a different type of infrastructure. We excluded studies that assessed collisions that occurred as a result of competitive cycling. Two review authors examined the titles and

Stable carbon isotopic compositions of low-molecular-weight dicarboxylic acids, glyoxylic acid and glyoxal in tropical aerosols: implications for photochemical processes of organic aerosols

Directory of Open Access Journals (Sweden)

Stelyus L. Mkoma

2014-10-01

Full Text Available Tropical aerosols of PM2.5 and PM10 were collected at a rural site in Morogoro, Tanzania (East Africa, and analysed for stable carbon isotopic composition (δ13C of dicarboxylic acids (C2–C9, glyoxylic acid (ωC2 and glyoxal (Gly using gas chromatography/isotope ratio mass spectrometer. PM2.5 samples showed that δ13C of oxalic (C2 acid are largest (mean, −18.3±1.7‰ followed by malonic (C3, −19.6±1.0‰ and succinic (C4, −21.8±2.2‰ acids, whereas those in PM10 are a little smaller: −19.9±3.1‰ (C2, −20.2±2.7‰ (C3 and −23.3±3.2‰ (C4. The δ13C of C2–C4 diacids showed a decreasing trend with an increase in carbon numbers. The higher δ13C values of oxalic acid can be explained by isotopic enrichment of 13C in the remaining C2 due to the atmospheric decomposition of oxalic acid or its precursors. δ13C of ωC2 and Gly that are precursors of oxalic acid also showed larger values (mean, −22.5‰ and −20.2‰, respectively in PM2.5 than those (−26.7‰ and −23.7‰ in PM10. The δ13C values of ωC2 and Gly are smaller than those of C2 in both PM2.5 and PM10. On the other hand, azelaic acid (C9; mean, −28.5‰ is more depleted in 13C, which is consistent with the previous knowledge; that is, C9 is produced by the oxidation of unsaturated fatty acids emitted from terrestrial higher plants. A significant enrichment of 13C in oxalic acid together with its negative correlations with relative abundance of C2 in total diacids and ratios of water-soluble organic carbon and organic carbon further support that a photochemical degradation of oxalic acid occurs during long-range transport from source regions.

Ceramic research on transformational superplasticity and stoichiometry effects on fracture. Research progress report, June 1, 1975--May 31, 1976

International Nuclear Information System (INIS)

Bradt, R.C.; Hoke, J.H.

1976-01-01

The progress of the program is reviewed by treating each of the areas separately. In the superplasticity investigation, the results of the Bi 2 WO 6 and Bi 2 MoO 3 systems are discussed both in terms of the transformational deformation and also the thermal cycling growth phenomenon. The growth phenomenon on thermal cycling through the phase transition shows some interesting bulk and microstructural features in terms of specimen strain and highly anisotropic grain growth. The stoichiometry effects on the fracture (K/sub Ic/ and K-V behavior) of TiO/sub 2-x/ and Fe/sub 1-x/ are reviewed as that study has been completed. Progress on the MgO . X Al 2 O 3 system is discussed

AFCT/TFCT/ISFS Program. Technical progress report for the period October 1, 1977--December 31, 1977

Energy Technology Data Exchange (ETDEWEB)

Hill, O.F. (comp.)

1978-02-01

This is the eighth in a series of quarterly progress reports on studies performed for the Alternate Fuel Cycle Technologies/Thorium Fuel Cycle Technologies/International Spent Fuel Receipt and Storage (AFCT/TFCT/ISFS) Program, formerly the LWR Fuel Recycle Program. This program is designed to provide information needed by industry to close the back end of the power reactor fuel cycle. During the past quarter, studies were conducted in the following tasks: Survey of Current Technology of Fuel Handling Techniques; Investigation of Air Cleaning Processes for Removing Tributyl Phosphate (TBP) from Off-Gas Streams; Study of Iodine Chemistry in Process Solutions; Electropolishing to Decontaminate Metallic Waste from Alternate and Thorium Converter Fuel Cycles; and U.S. Scale Transport, Dispersion and Removal Mode Comparison Safety Criticality Experiments. (11 figs., 7 tables)

Biological effects of ionizing radiation at the molecular, cellular, and organismal levals. Triannual progress report, July 15, 1974--October 14, 1977

International Nuclear Information System (INIS)

Lange, C.S.

1977-01-01

Progress is reported on the following studies: organization and repair of DNA; size measurement of DNA by means of the ultracentrifuge; effects of hydroxyurea, cycloheximide, and methylmercury on cell cycle progression; absence of an effect of photoreactivation on sublethal damage repair in a photoreactivating Wallaby cell line; and the control of differentiation and tissue polarity in planarians

Integrating life cycle assessment into managing potential EHS risks of engineered nanomaterials: reviewing progress to date

International Nuclear Information System (INIS)

Walker, William C.; Bosso, Christopher J.; Eckelman, Matthew; Isaacs, Jacqueline A.; Pourzahedi, Leila

2015-01-01

The 2011 National Nanotechnology Initiative’s Environmental Health and Safety Research Strategy stressed the need for research to integrate life cycle considerations into risk management and, then, to better integrate risk assessment into decisionmaking on environmental, health, and safety (EHS) dimensions of nanomanufacturing. This paper reviews scholarly articles published 2010–2015 that in some way apply life cycle analysis to nanotechnology to assess the extent to which current research reflects the priorities lain out in the NNI report. As the NNI’s focus was primarily on the “responsible development of nanotechnology” we also focus our examination on the ways in which LCA, in concert with other methodologies, can provide utility to decision makers facing the challenge of implementing that broad goal. We explore some of the challenges and opportunities inherent in using LCA, a tool built to optimize manufacturing decisions, as a guide for policy formulation or tool for policy implementation

Integrating life cycle assessment into managing potential EHS risks of engineered nanomaterials: reviewing progress to date

Energy Technology Data Exchange (ETDEWEB)

Walker, William C.; Bosso, Christopher J., E-mail: c.bosso@neu.edu [Northeastern University, School of Public Policy and Urban Affairs (United States); Eckelman, Matthew [Northeastern University, Department of Civil and Environmental Engineering (United States); Isaacs, Jacqueline A. [Northeastern University, Department of Mechanical and Industrial Engineering (United States); Pourzahedi, Leila [Northeastern University, Department of Civil and Environmental Engineering (United States)

2015-08-15

The 2011 National Nanotechnology Initiative’s Environmental Health and Safety Research Strategy stressed the need for research to integrate life cycle considerations into risk management and, then, to better integrate risk assessment into decisionmaking on environmental, health, and safety (EHS) dimensions of nanomanufacturing. This paper reviews scholarly articles published 2010–2015 that in some way apply life cycle analysis to nanotechnology to assess the extent to which current research reflects the priorities lain out in the NNI report. As the NNI’s focus was primarily on the “responsible development of nanotechnology” we also focus our examination on the ways in which LCA, in concert with other methodologies, can provide utility to decision makers facing the challenge of implementing that broad goal. We explore some of the challenges and opportunities inherent in using LCA, a tool built to optimize manufacturing decisions, as a guide for policy formulation or tool for policy implementation.

Perturbation of DNA replication and cell cycle progression by commonly used [3H]thymidine labeling protocols

International Nuclear Information System (INIS)

Hoy, C.A.; Lewis, E.D.; Schimke, R.T.

1990-01-01

The effect of tritiated thymidine incorporation on DNA replication was studied in Chinese hamster ovary cells. Rapidly eluting (small) DNA from cells labeled with 2 microCi of [ 3 H]thymidine per ml (200 microCi/mmol) for 60 min matured to a large nonelutable size within approximately 2 to 4 h, as measured by the alkaline elution technique. However, DNA from cells exposed to 10 microCi of [ 3 H]thymidine per ml (66 microCi/mmol) was more rapidly eluting initially and did not mature to a nonelutable size during subsequent incubation. Semiconservative DNA replication measured by cesium chloride gradient analysis of bromodeoxyuridine-substituted DNA was also found to be affected by the final specific activity of the [ 3 H]thymidine used in the labeling protocol. Dramatic cell cycle perturbations accompanied these effects on DNA replication, suggesting that labeling protocols commonly used to study DNA metabolism produce aberrant DNA replication and subsequent cell cycle perturbations

Quantitative application study on the control system of contract progress

International Nuclear Information System (INIS)

Hu Xiaocong; Kang Rujie; Zhan Li

2012-01-01

Quantitative application study on the control system of contract progress, which is based on project management theory and PDCA cycle methods, provides a new way for the contract business management of enterprise, in line with the current situation and the nuclear power enterprise performance management needs. The concept of the system, system development, program design and development of ERP (VBA design) which come from the work experience summary of business managers are convenient and feasible in practical applications. By way of the applications in 2009, 2010, 2011 three-year overhaul contract management and continuous adjustment it has become an important business management tool, which not only effectively guaranteed the contract time and efficiency, but also combines the performance management and contract progress management. This study has provided useful reference for the enterprise management. (authors)

Cell cycle age dependence for radiation-induced G2 arrest: evidence for time-dependent repair

International Nuclear Information System (INIS)

Rowley, R.

1985-01-01

Exponentially growing eucaryotic cells, irradiated in interphase, are delayed in progression to mitosis chiefly by arrest in G 2 . The sensitivity of Chinese hamster ovary cells to G 2 arrest induction by X rays increases through the cell cycle, up to the X-ray transition point (TP) in G 2 . This age response can be explained by cell cycle age-dependent changes in susceptibility of the target(s) for G 2 arrest and/or by changes in capability for postirradiation recovery from G 2 arrest damage. Discrimination between sensitivity changes and repair phenomena is possible only if the level of G 2 arrest-causing damage sustained by a cell at the time of irradiation and the level ultimately expressed as arrest can be determined. The ability of caffeine to ameliorate radiation-induced G 2 arrest, while inhibiting repair of G 2 arrest-causing damage makes such an analysis possible. In the presence of caffeine, progression of irradiated cells was relatively unperturbed, but on caffeine removal, G 2 arrest was expressed. The duration of G 2 arrest was independent of the length of the prior caffeine exposure. This finding indicates that the target for G 2 arrest induction is present throughout the cell cycle and that the level of G 2 arrest damage incurred is initially constant for all cell cycle phases. The data are consistent with the existence of a time-dependent recovery mechanism to explain the age dependence for radiation induction of G 2 arrest

Evaluation of denatured thorium fuel cycles in pressurized water reactors

International Nuclear Information System (INIS)

Matzie, R.A.; Rec, J.R.; Terney, A.N.

1977-01-01

A developing national energy policy that is based in part on a substantial expansion of the LWR-based electrical generating capacity with deferment of the LMFBR has prompted a re-evaluation of our nuclear fuel resources and their utilization. The ancillary policy of minimizing nuclear weapons proliferation through diversion of bred fissile material has left in doubt the viability of fuel recycling as a means of extending these fuel resources. A substantial, government-sponsored effort is in progress to examine alternate fuel cycles and advanced reactor concepts which can lead to improved resource utilization while minimizing proliferation potential. This paper evaluates several improved fuel cycles for use in current design PWRs and develops selected scenarios for their use within the framework of the safeguarded Nuclear Energy Center (NEC) concept

Assessment of Proliferation Resistance of Closed Nuclear Fuel Cycle System with Sodium Cooled Fast Reactors Using INPRO Evaluation Methodology

International Nuclear Information System (INIS)

Kim, Young In; Hahn, Do Hee; Won, Byung Chool; Lee, Dong Uk

2007-11-01

Using the INPRO methodology, the proliferation resistance of an innovative nuclear energy system(INS) defined as a closed nuclear fuel cycle system consisting of KALIMER and pyroprocessing, has been assessed. Considering a very early development stage of the INS concept, the PR assessment is carried out based on intrinsic features, if required information and data are not available. The PR assessment of KALIMER and JSFR using the INPRO methodology affirmed that an adequate proliferation resistance has been achieved in both INSs CNFC-SFR, considering the assessor's progress and maturity of design development. KALIMER and JSFR are developed or being developed conforming to the targets and criteria defined for developing Gen IV nuclear reactor system. Based on these assessment results, proliferation resistance and physical protection(PR and PP) of KALIMER and JSFR are evaluated from the viewpoint of requirements for future nuclear fuel cycle system. The envisioned INSs CNFC-SFR rely on active plutonium management based on a closed fuel cycle, in which a fissile material is recycled in an integrated fuel cycle facility within proper safeguards. There is no isolated plutonium in the closed fuel cycle. The material remains continuously in a sequence of highly radioactive matrices within inaccessible facilities. The proliferation resistance assessment should be an ongoing analysis that keeps up with the progress and maturity of the design of Gen IV SFR

Cell cycle effects of L-sulforaphane, a major antioxidant from cruciferous vegetables: The role of the anaphase promoting complex.

Science.gov (United States)

Shelley, Zhaoping; Royce, Simon G; Ververis, Katherine; Karagiannis, Tom C

2014-01-01

L-sulforaphane (LSF) is a natural isothiocyanate found in cruciferous vegetables particularly broccoli. LSF has been identified as a potent antioxidant and anti-cancer agent and is widely known to regulate phase II detoxifying enzymes and induce cell cycle arrest or apoptosis in malignant cells in vitro and in vivo. Previous studies have found significant G2/M cell cycle arrest in response to LSF in various model of cancer and results have mainly been attributed to increased cyclin B1 protein levels and increased p21expression. Using genome-wide mRNA-Seq analysis we provide insights into the molecular mechanisms of action of LSF to identify a key pathway in cell cycle progression - the role of the anaphase promoting complex (APC) pathway. We evaluated gene expression changes in human erythroleukemic K562 cells following treatment with 15 μM LSF for 48h and compared them to immortalized human keratinocytes, human microvascular endothelial cells (HMEC-1) cells and normal human umbilical endothelial cells (HUVEC). We identified disparate gene expression changes in response to LSF between malignant and normal cells and immortalized cell lines. The results highlight significant down-regulation of kinase CDK1 which is suggestive that the existence and activity of APC/CDC20 complex will be inhibited along with its associated down-stream degradation of key cell cycle regulators preventing cell cycle progression from mitotic exit.

Assessment of Proliferation Resistance of Closed Nuclear Fuel Cycle System with Sodium Cooled Fast Reactors Using INPRO Evaluation Methodology

Energy Technology Data Exchange (ETDEWEB)

Kim, Young In; Hahn, Do Hee; Won, Byung Chool; Lee, Dong Uk

2007-11-15

Using the INPRO methodology, the proliferation resistance of an innovative nuclear energy system(INS) defined as a closed nuclear fuel cycle system consisting of KALIMER and pyroprocessing, has been assessed. Considering a very early development stage of the INS concept, the PR assessment is carried out based on intrinsic features, if required information and data are not available. The PR assessment of KALIMER and JSFR using the INPRO methodology affirmed that an adequate proliferation resistance has been achieved in both INSs CNFC-SFR, considering the assessor's progress and maturity of design development. KALIMER and JSFR are developed or being developed conforming to the targets and criteria defined for developing Gen IV nuclear reactor system. Based on these assessment results, proliferation resistance and physical protection(PR and PP) of KALIMER and JSFR are evaluated from the viewpoint of requirements for future nuclear fuel cycle system. The envisioned INSs CNFC-SFR rely on active plutonium management based on a closed fuel cycle, in which a fissile material is recycled in an integrated fuel cycle facility within proper safeguards. There is no isolated plutonium in the closed fuel cycle. The material remains continuously in a sequence of highly radioactive matrices within inaccessible facilities. The proliferation resistance assessment should be an ongoing analysis that keeps up with the progress and maturity of the design of Gen IV SFR.

Industrial integration of the fuel cycle in Argentina

International Nuclear Information System (INIS)

Koll, J.H.; Kittl, J.E.; Parera, C.A.; Coppa, R.C.; Aguirre, E.J.

1977-01-01

The paper describes the power reactor construction programme in Argentina for the period 1976-1985, on the basis of which the nuclear fuel requirements have been determined. Activities connected with the fuel cycle commenced in 1950 in Argentina with the prospection and working of uranium deposits. On the basis of the nuclear power programme described, plans have been drawn up for the establishment of the industrial plants that will be needed to ensure the domestic supply of fuel. The demand for fuel is correlated with the availability of uranium resources and it is shown to be desirable from the technical, economic and industrial point of view to integrate the front end of the fuel cycle, keeping the irradiation aspects and the tail end at the development level. The authors report the progress that has been made in this field and describe current programmes covering prospection, concentrate production, nuclear purification, conversion to uranium dioxide, production of special alloys and fuel element fabrication. (author)

Industrial integration of the fuel cycle in Argentina

International Nuclear Information System (INIS)

Koll, J.H.; Kittl, J.E.; Parera, C.A.; Coppa, R.C.; Aguirre, E.J.

1983-01-01

The power-reactor construction program in Argentina for the period 1976-1985 is described on the basis of which the nuclear-fuel requirements have been determined. Activities connected with the fuel cycle commenced in 1950 in Argentina with the prospection and working of uranium deposits. On the basis of the nuclear power program described, plans have been drawn up for the establishment of the industrial plants that will be needed to ensure the domestic supply of fuel. The demand for fuel is correlated with the availability of uranium resoures and it is shown to be desirable from the technical, economic and industrial point of view to integrate the front end of the fuel cycle, keeping the irradiation aspects and the tail end at the development level. Progress made in this field and current programs covering exploration, concentrate production, nuclear purification, conversion to uranium dioxide, production of special alloys and fuel element fabrication are described

Mineral cycling in soil and litter arthropod food chains. Annual progress report, February 1, 1983-January 31, 1984

International Nuclear Information System (INIS)

Crossley, D.A. Jr.

1983-01-01

This annual report describes progress in research on the influence of soil fauna on the general process of terrestrial decomposition. The major goal is to investigate the regulation of decomposition by soil arthropods. Methods have included radioactive tracer measurements of food chain dynamics, rates of nutrient or mineral element flow during decomposition, and simulation modeling. This year's report describes significant progress in defining the influence of soil arthropods in stimulating microbial immobilization of nutrients. Preliminary efforts to define the importance of the soil-litter macroarthropods are also reported

Optimum gas turbine cycle for combined cycle power plant

International Nuclear Information System (INIS)

Polyzakis, A.L.; Koroneos, C.; Xydis, G.

2008-01-01

The gas turbine based power plant is characterized by its relatively low capital cost compared with the steam power plant. It has environmental advantages and short construction lead time. However, conventional industrial engines have lower efficiencies, especially at part load. One of the technologies adopted nowadays for efficiency improvement is the 'combined cycle'. The combined cycle technology is now well established and offers superior efficiency to any of the competing gas turbine based systems that are likely to be available in the medium term for large scale power generation applications. This paper has as objective the optimization of a combined cycle power plant describing and comparing four different gas turbine cycles: simple cycle, intercooled cycle, reheated cycle and intercooled and reheated cycle. The proposed combined cycle plant would produce 300 MW of power (200 MW from the gas turbine and 100 MW from the steam turbine). The results showed that the reheated gas turbine is the most desirable overall, mainly because of its high turbine exhaust gas temperature and resulting high thermal efficiency of the bottoming steam cycle. The optimal gas turbine (GT) cycle will lead to a more efficient combined cycle power plant (CCPP), and this will result in great savings. The initial approach adopted is to investigate independently the four theoretically possible configurations of the gas plant. On the basis of combining these with a single pressure Rankine cycle, the optimum gas scheme is found. Once the gas turbine is selected, the next step is to investigate the impact of the steam cycle design and parameters on the overall performance of the plant, in order to choose the combined cycle offering the best fit with the objectives of the work as depicted above. Each alterative cycle was studied, aiming to find the best option from the standpoint of overall efficiency, installation and operational costs, maintainability and reliability for a combined power

Exploring the Underlying Mechanisms of the Xenopus laevis Embryonic Cell Cycle.

Science.gov (United States)

Zhang, Kun; Wang, Jin

2018-05-31

The cell cycle is an indispensable process in proliferation and development. Despite significant efforts, global quantification and physical understanding are still challenging. In this study, we explored the mechanisms of the Xenopus laevis embryonic cell cycle by quantifying the underlying landscape and flux. We uncovered the Mexican hat landscape of the Xenopus laevis embryonic cell cycle with several local basins and barriers on the oscillation path. The local basins characterize the different phases of the Xenopus laevis embryonic cell cycle, and the local barriers represent the checkpoints. The checkpoint mechanism of the cell cycle is revealed by the landscape basins and barriers. While landscape shape determines the stabilities of the states on the oscillation path, the curl flux force determines the stability of the cell cycle flow. Replication is fundamental for biology of living cells. We quantify the input energy (through the entropy production) as the thermodynamic requirement for initiation and sustainability of single cell life (cell cycle). Furthermore, we also quantify curl flux originated from the input energy as the dynamical requirement for the emergence of a new stable phase (cell cycle). This can provide a new quantitative insight for the origin of single cell life. In fact, the curl flux originated from the energy input or nutrition supply determines the speed and guarantees the progression of the cell cycle. The speed of the cell cycle is a hallmark of cancer. We characterized the quality of the cell cycle by the coherence time and found it is supported by the flux and energy cost. We are also able to quantify the degree of time irreversibility by the cross correlation function forward and backward in time from the stochastic traces in the simulation or experiments, providing a way for the quantification of the time irreversibility and the flux. Through global sensitivity analysis upon landscape and flux, we can identify the key elements for

Cytotoxicity of diacetoxyscirpenol is associated with apoptosis by activation of caspase-8 and interruption of cell cycle progression by down-regulation of cdk4 and cyclin B1 in human Jurkat T cells

International Nuclear Information System (INIS)

Jun, Do Youn; Kim, Jun Seok; Park, Hae Sun; Song, Woo Sun; Bae, Young Seuk; Kim, Young Ho

2007-01-01

To understand the mechanism underlying T-cell toxicity of diacetoxyscirpenol (DAS) from Fusarium sambucinum, its apoptogenic as well as growth retardation activity was investigated in human Jurkat T cells. Exposure to DAS (0.01-0.15 μM) caused apoptotic DNA fragmentation along with caspase-8 activation, Bid cleavage, mitochondrial cytochrome c release, activation of caspase-9 and caspase-3, and PARP degradation, without any alteration in the levels of Fas or FasL. Under these conditions, necrosis was not accompanied. The cytotoxicity of DAS was not blocked by the anti-Fas neutralizing antibody ZB-4. Although the DAS-induced apoptotic events were completely prevented by overexpression of Bcl-xL, the cells overexpressing Bcl-xL were unable to divide in the presence of DAS, resulting from the failure of cell cycle progression possibly due to down-regulation in the protein levels of cdk4 and cyclin B1. The DAS-mediated apoptosis and activation of caspase-8, -9, and -3 were abrogated by either pan-caspase inhibitor (z-VAD-fmk) or caspase-8 inhibitor (z-IETD-fmk). While the DAS-mediated apoptosis and activation of caspase-9 and caspase-3 were slightly suppressed by the mitochondrial permeability transition pore inhibitor (CsA), both caspase-8 activation and Bid cleavage were not affected by CsA. The activated normal peripheral T cells possessed a similar susceptibility to the cytotoxicity of DAS. These results demonstrate that the T-cell toxicity of DAS is attributable to not only apoptosis initiated by caspase-8 activation and subsequent mitochondrion-dependent or -independent activation of caspase cascades, which can be regulated by Bcl-xL, but also interruption of cell cycle progression caused by down-regulation of cdk4 and cyclin B1 proteins

Cyclin D1 overexpression, cell cycle progression and radiosensitivity in MBP cells

International Nuclear Information System (INIS)

Wu Lijun; Yu Zengliang

2000-11-01

Clones that exhibited a minimum of 7-8 fold cyclin D1 level above the parent cell lines or the vector control were obtained after transfected with the entire coding sequence of human 1.1 kb cyclin D1 cDNA. Studies showed that there was no significant difference in Radiosensitivity between over-expressing cyclin D1 and control cultures from either mouse or human origin. Using flow cytometry to access cell cycle distribution in the exponentially growth cultures of MCF10F-D1-21 and MCF10F-V-3, it was found that there was a 50 percent increase in the proportion of G2/M phase cells and 5.3 percent decrease in the proportion of G0/G1 phase cells in MCF10F-D1-21 comparing with MCF10F-V-3, though they were with the same proportion of cells in S phase

The Mammalian Cell Cycle Regulates Parvovirus Nuclear Capsid Assembly

Science.gov (United States)

Riolobos, Laura; Domínguez, Carlos; Kann, Michael; Almendral, José M.

2015-01-01

It is unknown whether the mammalian cell cycle could impact the assembly of viruses maturing in the nucleus. We addressed this question using MVM, a reference member of the icosahedral ssDNA nuclear parvoviruses, which requires cell proliferation to infect by mechanisms partly understood. Constitutively expressed MVM capsid subunits (VPs) accumulated in the cytoplasm of mouse and human fibroblasts synchronized at G0, G1, and G1/S transition. Upon arrest release, VPs translocated to the nucleus as cells entered S phase, at efficiencies relying on cell origin and arrest method, and immediately assembled into capsids. In synchronously infected cells, the consecutive virus life cycle steps (gene expression, proteins nuclear translocation, capsid assembly, genome replication and encapsidation) proceeded tightly coupled to cell cycle progression from G0/G1 through S into G2 phase. However, a DNA synthesis stress caused by thymidine irreversibly disrupted virus life cycle, as VPs became increasingly retained in the cytoplasm hours post-stress, forming empty capsids in mouse fibroblasts, thereby impairing encapsidation of the nuclear viral DNA replicative intermediates. Synchronously infected cells subjected to density-arrest signals while traversing early S phase also blocked VPs transport, resulting in a similar misplaced cytoplasmic capsid assembly in mouse fibroblasts. In contrast, thymidine and density arrest signals deregulating virus assembly neither perturbed nuclear translocation of the NS1 protein nor viral genome replication occurring under S/G2 cycle arrest. An underlying mechanism of cell cycle control was identified in the nuclear translocation of phosphorylated VPs trimeric assembly intermediates, which accessed a non-conserved route distinct from the importin α2/β1 and transportin pathways. The exquisite cell cycle-dependence of parvovirus nuclear capsid assembly conforms a novel paradigm of time and functional coupling between cellular and virus life

Redefining Our Roles as Teachers, Learners, and Leaders through Continuous Cycles of Practitioner Inquiry

Science.gov (United States)

MacDonald, Michelina; Weller, Kristin

2017-01-01

Practitioner inquiry is an alternative form of professional learning that can result in significant changes in teacher practice and student learning. We share our evolution as teacher learners within our classrooms and teacher leaders within our school as we progressed through 10 years of continuous cycles of practitioner inquiry. Beginning as…

The feasibility study on commercialized fast reactor cycle system

International Nuclear Information System (INIS)

Noda, Hiroshi

2002-01-01

The feasibility study on commercialized Fast Reactor cycle system (FS) has been carried out by a joint team with the participation of all parties concerned in Japan since July, 1999. It aims to clarify various perspectives for commercialized fast reactor cycle system and also suggest development strategies to diverse social needs in the 21 st century. The FS consists of several phases. The phase 1 has progressed as planned and the highly feasible candidate concepts with innovative technologies have been screened out among a wide variety of concepts. During the phase 2, approximately five years after the phase 1, the in-depth design studies and engineering scale tests of key technologies are being conducted to verify and validate the feasibility of screened candidate concepts. At the end of the phase 2, a few promising concepts will be selected with their R and D tasks. The paper describes the results of the phase 1, the activities of the phase 2 and the new concept related to the fast reactor fuel cycle focusing on the reduction in environmental burden, which is one of key factors to sustain the nuclear power generation in the 21 st century

Results of cycling with battery charging management; Resultats de cyclage avec gestion de charge au niveau batterie

Energy Technology Data Exchange (ETDEWEB)

Verniolle, J.; Fernandez, C. [European Space Research and Technology Centre, Noordwijk (Netherlands)

1996-12-31

In order to investigate the charging mode of an in-series assembly of lithium-carbon battery cells, a test has been performed on 5 commercial cells (18650) of 0.95 Ah nominal capacity. Results show that it is possible to cycle the cells at 80% of their output capacities during more than 2000 cycles. The management of the battery consists in maintaining a constant battery voltage as soon as a cell reaches its limit voltage during constant current charging. The initial dispersion of cells has been maintained practically constant during the cycling and the charge state of all cells has decreased progressively. (J.S.)

Results of cycling with battery charging management; Resultats de cyclage avec gestion de charge au niveau batterie

Energy Technology Data Exchange (ETDEWEB)

Verniolle, J; Fernandez, C [European Space Research and Technology Centre, Noordwijk (Netherlands)

1997-12-31

In order to investigate the charging mode of an in-series assembly of lithium-carbon battery cells, a test has been performed on 5 commercial cells (18650) of 0.95 Ah nominal capacity. Results show that it is possible to cycle the cells at 80% of their output capacities during more than 2000 cycles. The management of the battery consists in maintaining a constant battery voltage as soon as a cell reaches its limit voltage during constant current charging. The initial dispersion of cells has been maintained practically constant during the cycling and the charge state of all cells has decreased progressively. (J.S.)

Predictive value of sperm morphology and progressively motile sperm count for pregnancy outcomes in intrauterine insemination.

Science.gov (United States)

Lemmens, Louise; Kos, Snjezana; Beijer, Cornelis; Brinkman, Jacoline W; van der Horst, Frans A L; van den Hoven, Leonie; Kieslinger, Dorit C; van Trooyen-van Vrouwerff, Netty J; Wolthuis, Albert; Hendriks, Jan C M; Wetzels, Alex M M

2016-06-01

To investigate the value of sperm parameters to predict an ongoing pregnancy outcome in couples treated with intrauterine insemination (IUI), during a methodologically stable period of time. Retrospective, observational study with logistic regression analyses. University hospital. A total of 1,166 couples visiting the fertility laboratory for their first IUI episode, including 4,251 IUI cycles. None. Sperm morphology, total progressively motile sperm count (TPMSC), and number of inseminated progressively motile spermatozoa (NIPMS); odds ratios (ORs) of the sperm parameters after the first IUI cycle and the first finished IUI episode; discriminatory accuracy of the multivariable model. None of the sperm parameters was of predictive value for pregnancy after the first IUI cycle. In the first finished IUI episode, a positive relationship was found for ≤4% of morphologically normal spermatozoa (OR 1.39) and a moderate NIPMS (5-10 million; OR 1.73). Low NIPMS showed a negative relation (≤1 million; OR 0.42). The TPMSC had no predictive value. The multivariable model (i.e., sperm morphology, NIPMS, female age, male age, and the number of cycles in the episode) had a moderate discriminatory accuracy (area under the curve 0.73). Intrauterine insemination is especially relevant for couples with moderate male factor infertility (sperm morphology ≤4%, NIPMS 5-10 million). In the multivariable model, however, the predictive power of these sperm parameters is rather low. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The cost analysis of hydrogen life cycle in China

International Nuclear Information System (INIS)

Yao, Fei; Jia, Yuan; Mao, Zongqiang

2010-01-01

Currently, the increasing price of oil and the possibility of global energy crisis demand for substitutive energy to replace fossil energy. Many kinds of renewable energy have been considered, such as hydrogen, solar energy, and wind energy. Many countries including China have their own plan to support the research of hydrogen, because of its premier features. But, at present, the cost of hydrogen energy production, storage and transportation process is higher than that of fossil energy and its commercialization progress is slow. Life cycle cost analysis (LCCA) was used in this paper to evaluate the cost of hydrogen energy throughout the life cycle focused on the stratagem selection, to demonstrate the costs of every step and to discuss their relationship. Finally, the minimum cost program is as follows: natural gas steam reforming - high-pressure hydrogen bottles transported by car to hydrogen filling stations - hydrogen internal-combustion engines. (author)

Analysis of redox relationships in the plant cell cycle: determinations of ascorbate, glutathione and poly (ADPribose)polymerase (PARP) in plant cell cultures.

Science.gov (United States)

Foyer, Christine H; Pellny, Till K; Locato, Vittoria; De Gara, Laura

2008-01-01

Reactive oxygen species (ROS) and low molecular weight antioxidants, such as glutathione and ascorbate, are powerful signaling molecules that participate in the control of plant growth and development, and modulate progression through the mitotic cell cycle. Enhanced reactive oxygen species accumulation or low levels of ascorbate or glutathione cause the cell cycle to arrest and halt progression especially through the G1 checkpoint. Plant cell suspension cultures have proved to be particularly useful tools for the study of cell cycle regulation. Here we provide effective and accurate methods for the measurement of changes in the cellular ascorbate and glutathione pools and the activities of related enzymes such poly (ADP-ribose) polymerase during mitosis and cell expansion, particularly in cell suspension cultures. These methods can be used in studies seeking to improve current understanding of the roles of redox controls on cell division and cell expansion.

Studies on regulation of the cell cycle in fission yeast.

Directory of Open Access Journals (Sweden)

Miroslava Požgajová

2015-05-01

Full Text Available All living organisms including plants and animals are composed of millions of cells. These cells perform different functions for the organism although they possess the same chromosomes and carry the same genetic information. Thus, to be able to understand multicellular organism we need to understand the life cycle of individual cells from which the organism comprises. The cell cycle is the life cycle of a single cell in the plant or animal body. It involves series of events in which components of the cell doubles and afterwards equally segregate into daughter cells. Such process ensures growth of the organism, and specialized reductional cell division which leads to production of gamets, assures sexual reproduction. Cell cycle is divided in the G1, S, G2 and M phase. Two gap-phases (G1 and G2 separate S phase (or synthesis and M phase which stays either for mitosis or meiosis. Essential for normal life progression and reproduction is correct chromosome segregation during mitosis and meiosis. Defects in the division program lead to aneuploidy, which in turn leads to birth defects, miscarriages or cancer. Even thou, researchers invented much about the regulation of the cell cycle, there is still long way to understand the complexity of the regulatory machineries that ensure proper segregation of chromosomes. In this paper we would like to describe techniques and materials we use for our studies on chromosome segregation in the model organism Schizosaccharomyces pombe.

Cycles and Common Cycles in Property and Related Sectors

OpenAIRE

Peijie Wang

2003-01-01

This paper examines cycles and common cycles in the property market and the economy. While focusing on common cycles, the study also incorporates common trends in the meantime, so it covers the whole spectrum of dynamic analysis. It has been found that property shares common cycles, particularly with those sectors that are the user markets of property. The mechanisms of common cycles and the relative magnitudes of cycles of the sectors related to property are discussed to shed light on proper...

Microstructural evolution during hydrogen sorption cycling of Mg-FeTi nanolayered composites

Energy Technology Data Exchange (ETDEWEB)

Kalisvaart, W.P., E-mail: pkalisvaart@gmail.com [Chemical and Materials Engineering, University of Alberta and National Research Council Canada, National Institute for Nanotechnology, Edmonton, AB, T6G 2V4 (Canada); Kubis, Alan; Danaie, Mohsen; Amirkhiz, Babak Shalchi [Chemical and Materials Engineering, University of Alberta and National Research Council Canada, National Institute for Nanotechnology, Edmonton, AB, T6G 2V4 (Canada); Mitlin, David, E-mail: dmitlin@ualberta.ca [Chemical and Materials Engineering, University of Alberta and National Research Council Canada, National Institute for Nanotechnology, Edmonton, AB, T6G 2V4 (Canada)

2011-03-15

This paper describes the microstructural evolution of Mg-FeTi mutlilayered hydrogen storage materials during extended cycling. A 28 nm Mg-5 nm FeTi multilayer has comparable performance to a cosputtered material with an equivalent composition (Mg-10%Fe-10%Ti), which is included as a baseline case. At 200 deg. C, the FeTi layers act as a barrier, preventing agglomeration of Mg particles. At 300 deg. C, the initial structure of the multilayer is preserved up to 35 cycles, followed by fracturing of the Mg layers in the in-plane direction and progressive delamination of the FeTi layers as observed by electron microscopy. Concurrently, an increase in the Mg grain size was observed from 32 to 76 nm between cycles 35 and 300. As a result, the absorption kinetics deteriorate with cycling, although 90% of the total capacity is still absorbed within 2 min after as many as 300 cycles. The desorption kinetics, on the other hand, remain rapid and stable, and complete desorption of 4.6 wt.% H is achieved in 1.5 min at ambient desorption pressure. In addition to showing good hydrogen storage performance, multilayers are an excellent model system for studying the relation between microstructure and hydrogen absorption/desorption kinetics.

Microstructural evolution during hydrogen sorption cycling of Mg-FeTi nanolayered composites

International Nuclear Information System (INIS)

Kalisvaart, W.P.; Kubis, Alan; Danaie, Mohsen; Amirkhiz, Babak Shalchi; Mitlin, David

2011-01-01

This paper describes the microstructural evolution of Mg-FeTi mutlilayered hydrogen storage materials during extended cycling. A 28 nm Mg-5 nm FeTi multilayer has comparable performance to a cosputtered material with an equivalent composition (Mg-10%Fe-10%Ti), which is included as a baseline case. At 200 deg. C, the FeTi layers act as a barrier, preventing agglomeration of Mg particles. At 300 deg. C, the initial structure of the multilayer is preserved up to 35 cycles, followed by fracturing of the Mg layers in the in-plane direction and progressive delamination of the FeTi layers as observed by electron microscopy. Concurrently, an increase in the Mg grain size was observed from 32 to 76 nm between cycles 35 and 300. As a result, the absorption kinetics deteriorate with cycling, although 90% of the total capacity is still absorbed within 2 min after as many as 300 cycles. The desorption kinetics, on the other hand, remain rapid and stable, and complete desorption of 4.6 wt.% H is achieved in 1.5 min at ambient desorption pressure. In addition to showing good hydrogen storage performance, multilayers are an excellent model system for studying the relation between microstructure and hydrogen absorption/desorption kinetics.

Gene Expression Response of Trichophyton rubrum during Coculture on Keratinocytes Exposed to Antifungal Agents

Directory of Open Access Journals (Sweden)

Tatiana Takahasi Komoto

2015-01-01

Full Text Available Trichophyton rubrum is the most common causative agent of dermatomycoses worldwide, causing infection in the stratum corneum, nails, and hair. Despite the high prevalence of these infections, little is known about the molecular mechanisms involved in the fungal-host interaction, particularly during antifungal treatment. The aim of this work was to evaluate the gene expression of T. rubrum cocultured with keratinocytes and treated with the flavonoid trans-chalcone and the glycoalkaloid α-solanine. Both substances showed a marked antifungal activity against T. rubrum strain CBS (MIC = 1.15 and 17.8 µg/mL, resp.. Cytotoxicity assay against HaCaT cells produced IC50 values of 44.18 to trans-chalcone and 61.60 µM to α-solanine. The interaction of keratinocytes with T. rubrum conidia upregulated the expression of genes involved in the glyoxylate cycle, ergosterol synthesis, and genes encoding proteases but downregulated the ABC transporter TruMDR2 gene. However, both antifungals downregulated the ERG1 and ERG11, metalloprotease 4, serine proteinase, and TruMDR2 genes. Furthermore, the trans-chalcone downregulated the genes involved in the glyoxylate pathway, isocitrate lyase, and citrate synthase. Considering the urgent need for more efficient and safer antifungals, these results contribute to a better understanding of fungal-host interactions and to the discovery of new antifungal targets.

Effect of cra gene knockout together with edd and iclR genes knockout on the metabolism in Escherichia coli.

Science.gov (United States)

Sarkar, Dayanidhi; Siddiquee, Khandaker Al Zaid; Araúzo-Bravo, Marcos J; Oba, Takahiro; Shimizu, Kazuyuki

2008-11-01

To elucidate the physiological adaptation of Escherichia coli due to cra gene knockout, a total of 3,911 gene expressions were investigated by DNA microarray for continuous culture. About 50 genes were differentially regulated for the cra mutant. TCA cycle and glyoxylate shunt were down-regulated, while pentose phosphate (PP) pathway and Entner Doudoroff (ED) pathway were up-regulated in the cra mutant. The glucose uptake rate and the acetate production rate were increased with less acetate consumption for the cra mutant. To identify the genes controlled by Cra protein, the Cra recognition weight matrix from foot-printing data was developed and used to scan the whole genome. Several new Cra-binding sites were found, and some of the result was consistent with the DNA microarray data. The ED pathway was active in the cra mutant; we constructed cra.edd double genes knockout mutant to block this pathway, where the acetate overflowed due to the down-regulation of aceA,B and icd gene expressions. Then we further constructed cra.edd.iclR triple genes knockout mutant to direct the carbon flow through the glyoxylate pathway. The cra.edd.iclR mutant showed the least acetate production, resulting in the highest cell yield together with the activation of the glycolysis pathway, but the glucose consumption rate could not be improved.

Past and present of sediment and carbon biogeochemical cycling models

Directory of Open Access Journals (Sweden)

F. T. Mackenzie

2004-01-01

Full Text Available The global carbon cycle is part of the much more extensive sedimentary cycle that involves large masses of carbon in the Earth's inner and outer spheres. Studies of the carbon cycle generally followed a progression in knowledge of the natural biological, then chemical, and finally geological processes involved, culminating in a more or less integrated picture of the biogeochemical carbon cycle by the 1920s. However, knowledge of the ocean's carbon cycle behavior has only within the last few decades progressed to a stage where meaningful discussion of carbon processes on an annual to millennial time scale can take place. In geologically older and pre-industrial time, the ocean was generally a net source of CO2 emissions to the atmosphere owing to the mineralization of land-derived organic matter in addition to that produced in situ and to the process of CaCO3 precipitation. Due to rising atmospheric CO2 concentrations because of fossil fuel combustion and land use changes, the direction of the air-sea CO2 flux has reversed, leading to the ocean as a whole being a net sink of anthropogenic CO2. The present thickness of the surface ocean layer, where part of the anthropogenic CO2 emissions are stored, is estimated as of the order of a few hundred meters. The oceanic coastal zone net air-sea CO2 exchange flux has also probably changed during industrial time. Model projections indicate that in pre-industrial times, the coastal zone may have been net heterotrophic, releasing CO2 to the atmosphere from the imbalance between gross photosynthesis and total respiration. This, coupled with extensive CaCO3 precipitation in coastal zone environments, led to a net flux of CO2 out of the system. During industrial time the coastal zone ocean has tended to reverse its trophic status toward a non-steady state situation of net autotrophy, resulting in net uptake of anthropogenic CO2 and storage of carbon in the coastal ocean, despite the significant calcification

Progressive decrement PWM algorithm for minimum mean square error inverter output voltage

International Nuclear Information System (INIS)

Ghaeb, J.A.; Smadi, M.A.; Ababneh, M.

2011-01-01

Highlights: → The main contribution of this work is to provide a better performance for the power inverter operation. → The proposed technique splits the determined original pulse-width of an inverter operation in to many pulses. → The new approach extends the central pulse and shrinks the exterior pulses. → This is leading to an inverter output cycle close to the sinusoidal form of fewer harmonics. - Abstract: The paper proposes two modulation techniques for the power inverter. These new techniques are named progressive decrement PWM algorithm (PDPA) and progressive increment PWM algorithm (PIPA). Both techniques take the determined original pulse-width of an inverter operation and split it to many pulses. In the PDPA technique, the largest width is given to the middle pulse and the width of the boundary pulses is reduced progressively starting from the first boundary-pulse toward the last boundary-pulse. In the PIPA technique, there is a gradual increment instead of decrement. The two techniques have been proved that it can maintain the original pulse-width of the inverter operation. The new approach PDPA extends the central pulse and shrinks the exterior pulses, leading to an inverter output cycle close to the sinusoidal form of fewer harmonic contents. Simulation results are performed to evaluate the performances of the proposed techniques: PDPA and PIPA and to compare them with the well known methods. The main contribution of the proposed PDPA technique is that it provides a better performance for the most harmonic orders compared to the well established sinusoidal PWM technique.

Arabidopsis EST1/SMG7-like protein is a novel regulator of meiotic cell cycle progression

Czech Academy of Sciences Publication Activity Database

Riehs, N.; Akimcheva, S.; Bulánková, P.; Idol, R.; Široký, Jiří; Shippen, D.; Schweizer, D.; Říha, K.

2007-01-01

Roč. 274, č. 1 (2007), s. 71 ISSN 1742-464X. [32nd FEBS Congress - Molecular Machines. 07.07.2007-12.07.2007, Vienna] R&D Projects: GA ČR(CZ) GA522/06/0380 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : meiosis * Arabidopsis * cell cycle Subject RIV: BO - Biophysics

HCl removal using cycled carbide slag from calcium looping cycles

International Nuclear Information System (INIS)

Xie, Xin; Li, Yingjie; Wang, Wenjing; Shi, Lei

2014-01-01

Highlights: • Cycled carbide slag from calcium looping cycles is used to remove HCl. • The optimum temperature for HCl removal of cycled carbide slag is 700 °C. • The presence of CO 2 restrains HCl removal of cycled carbide slag. • CO 2 capture conditions have important effects on HCl removal of cycled carbide slag. • HCl removal capacity of carbide slag drops with cycle number rising from 1 to 50. - Abstract: The carbide slag is an industrial waste from chlor-alkali plants, which can be used to capture CO 2 in the calcium looping cycles, i.e. carbonation/calcination cycles. In this work, the cycled carbide slag from the calcium looping cycles for CO 2 capture was proposed to remove HCl in the flue gas from the biomass-fired and RDFs-fired boilers. The effects of chlorination temperature, HCl concentration, particle size, presence of CO 2 , presence of O 2 , cycle number and CO 2 capture conditions in calcium looping cycles on the HCl removal behavior of the carbide slag experienced carbonation/calcination cycles were investigated in a triple fixed-bed reactor. The chlorination product of the cycled carbide slag from the calcium looping after absorbing HCl is not CaCl 2 but CaClOH. The optimum temperature for HCl removal of the cycled carbide slag from the carbonation/calcination cycles is 700 °C. The chlorination conversion of the cycled carbide slag increases with increasing the HCl concentration. The cycled carbide slag with larger particle size exhibits a lower chlorination conversion. The presence of CO 2 decreases the chlorination conversions of the cycled carbide slag and the presence of O 2 has a trifling impact. The chlorination conversion of the carbide slag experienced 1 carbonation/calcination cycle is higher than that of the uncycled calcined sorbent. As the number of carbonation/calcination cycles increases from 1 to 50, the chlorination conversion of carbide slag drops gradually. The high calcination temperature and high CO 2

Cell cycle regulation of the BRCA1/acetyl-CoA-carboxylase complex.

Science.gov (United States)

Ray, H; Suau, F; Vincent, A; Dalla Venezia, N

2009-01-16

Germ-line alterations in BRCA1 are associated with an increased susceptibility to breast and ovarian cancer. The BRCA1 protein has been implicated in multiple cellular functions. We have recently demonstrated that BRCA1 reduces acetyl-CoA-carboxylase alpha (ACCA) activity through its phospho-dependent binding to ACCA, and further established that the phosphorylation of the Ser1263 of ACCA is required for this interaction. Here, to gain more insight into the cellular conditions that trigger the BRCA1/ACCA interaction, we designed an anti-pSer1263 antibody and demonstrated that the Ser1263 of ACCA is phosphorylated in vivo, in a cell cycle-dependent manner. We further showed that the interaction between BRCA1 and ACCA is regulated during cell cycle progression. Taken together, our findings reveal a novel mechanism of regulation of ACCA distinct from the previously described phosphorylation of Ser79, and provide new insights into the control of lipogenesis through the cell cycle.

UK Safeguards R and D Project progress report for the period July 1983 - April 1984

International Nuclear Information System (INIS)

Adams, J.M.

1984-10-01

Progress reports are presented on the following projects: centrifuge enrichment plant safeguards; stores safeguards and general accounting techniques; generic programmes (projects underlying many instrument systems (e.g. tamper proofing and indication; neutron interrogation systems); system studies); FBR fuel cycle safeguards; service programmes (services to the IAEA); exploratory and short projects. (U.K.)

AREVA Modular Steam Cycle – High Temperature Gas-Cooled Reactor Development Progress

International Nuclear Information System (INIS)

Lommers, L.; Shahrokhi, F.; Southworth, F.; Mayer, J. III

2014-01-01

The AREVA Steam Cycle – High Temperature Gas-Cooled Reactor (SCHTGR) is a modular graphite-moderated gas-cooled reactor currently being developed to support a wide variety of applications including industrial process heat, high efficiency electricity generation, and cogeneration. It produces high temperature superheated steam which makes it a good match for many markets currently dependent on fossil fuels for process heat. Moreover, the intrinsic safety characteristics of the SC-HTGR make it uniquely qualified for collocation with large industrial process heat users which is necessary for serving these markets. The NGNP Industry Alliance has selected the AREVA SC-HTGR as the basis for future development work to support commercial HTGR deployment. This paper provides a concise description of the SC-HTGR concept, followed by a summary of recent development activities. Since this concept was introduced, ongoing design activities have focused primarily on confirming key system capabilities and the suitability for potential future markets. These evaluations continue to confirm the suitability of the SC-HTGR for a variety of potential applications that are currently dependent on fossil fuels. (author)

Drug Delivery Research: The Invention Cycle.

Science.gov (United States)

Park, Kinam

2016-07-05

Controlled drug delivery systems have been successful in introducing improved formulations for better use of existing drugs and novel delivery of biologicals. The initial success of producing many oral products and some injectable depot formulations, however, reached a plateau, and the progress over the past three decades has been slow. This is likely due to the difficulties of formulating hydrophilic, high molecular weight drugs, such as proteins and nucleic acids, for targeting specific cells, month-long sustained delivery, and pulsatile release. Since the approaches that have served well for delivery of small molecules are not applicable to large molecules, it is time to develop new methods for biologicals. The process of developing future drug delivery systems, termed as the invention cycle, is proposed, and it starts with clearly defining the problems for developing certain formulations. Once the problems are well-defined, creative imagination examines all potential options and selects the best answer and alternatives. Then, innovation takes over to generate unique solutions for developing new formulations that resolve the previously identified problems. Ultimately, the new delivery systems will have to go through a translational process to produce the final formulations for clinical use. The invention cycle also emphasizes examining the reasons for success of certain formulations, not just the reasons for failure of many systems. Implementation of the new invention cycle requires new mechanisms of funding the younger generation of scientists and a new way of identifying their achievements, thereby releasing them from the burden of short-termism.

Safety considerations in the fast reactor fuel cycle

International Nuclear Information System (INIS)

Baker, A.R.; Burton, W.R.; Taylor, H.A.

1977-01-01

The fuel cycle safety problems for fast reactors, as compared with thermal reactors, are enhanced by the higher fissile content and heat rating of the fuel. Additionally recycling leads to the build up of substantial isotopes which contribute to the alpha and neutron hazards. The plutonium arisings in a nuclear power reactor programme extending into the next century are discussed. A requirement is to be able to return the product plutonium to a reactor about 9 months after the end of irradiation and it is anticipated that progress will be made slowly towards this fuel cycle, having regard to the necessity for maintaining safe and reliable operations. Consideration of the steps in the fuel cycle has indicated that it will be best to store the irradiated fuel on the reactor sites while I131 decays and decay heat falls before transporting and a suitable transport flask is being developed. Reprocessing development work is aimed at the key area of fuel breakdown, the inter-relation of the fuel characteristics on the dissolution of the plutonium and a solvent extract cycle leading to a product suitable for a co-located fabrication plant. Because of the high activity of recycled fuel it is considered that fabrication must move to a fully remote operation as is already the case for reprocessing, and a gel precipitation process producing a vibro compacted fuel is under development for this purpose. The waste streams from the processing plants must be minimised, processed for recovery of plutonium where applicable and then conditioned so that the final products released from the processing cycle are acceptable for ultimate disposal. The safety aspects reviewed cover protection of operators, containment of radioactive materials, criticality and regulation of discharges to the environment

WWER-1000 fuel cycles: current situation and outlook

International Nuclear Information System (INIS)

Kosourov, E.; Pavlov, V.; Pavlovichev, A.; Spirkin, E.; Shcherenko, A.

2013-01-01

Usage mode of nuclear fuel in WWER type reactor has been changed significantly till the moment of the first WWER-1000 commissioning. There are a lot of improvements, having an impact on the fuel cycle, have been implemented for units with WWER-1000. FA design and its constructional materials, FA fuel weight, burnable poison, usage mode of units and etc have been modified. As the result of development it has been designed a modern FA with rigid skeleton. As a whole it allows to use more efficient configurations of the core, to extend range of fuel cycle lengths and to provide good flexibility in the operation. In recent years there were in progress works on increasing FA uranium capacity. As the result there were developed two designs of the fuel rod: 1) the fuel column height of 3680 mm, diameters of the fuel pellet and its central hole of 7.6 and 1.2 mm respectively and 2) the fuel column height of 3530 mm, the fuel pellet diameter of 7.8 mm without the central hole. Such fuel rods have operating experience as a part of different FA designs. Positive operating experience was a base of new FA (TVS-4) development with the fuel column height of 3680 mm and the fuel pellet diameter of 7.8 mm without the central hole. The paper presents the overview of WWER-1000, AES-2006 and WWER-TOI fuel cycles based on FAs with fuel rod designs described above. There are demonstrated fuel cycle possibilities and its technical and economic characteristics. There are discussed problems of further fuel cycle improvements (fuel enrichment increase above 5 %, use of erbium as alternative burnable poison) and their impact on neutronics characteristics. (authors)

Purification, crystallization and preliminary X-ray analysis of isocitrate dehydrogenase kinase/phosphatase from Escherichia coli

International Nuclear Information System (INIS)

Zheng, Jimin; Lee, Daniel C.; Jia, Zongchao

2009-01-01

Isocitrate dehydrogenase kinase/phosphatase has been crystallized in three different crystal forms. Data were collected from each crystal form for structure determination. The Escherichia coli aceK gene encodes isocitrate dehydrogenase kinase/phosphatase (EC 2.7.11.5), a bifunctional protein that phosphorylates and dephosphorylates isocitrate dehydrogenase (IDH), resulting in its inactivation and activation, respectively. This reversible (de)phosphorylation directs isocitrate, an intermediate of the citric acid cycle, to either go through the full cycle or to enter the glyoxylate bypass. In the present study, the AceK protein from E. coli has been purified and crystallized. Three crystal forms were obtained from very similar crystallization conditions. The crystals belong to space groups P4 1 2 1 2, P3 2 21 and P2 1 2 1 2 1 and diffracted X-rays to resolutions of 2.9, 3.0 and 2.7 Å, respectively

Recent IAEA activities on CANDU-PHWR fuels and fuel cycles

International Nuclear Information System (INIS)

Inozemtsev, V.; Ganguly, C.

2005-01-01

Pressurized Heavy Water Reactors (PHWR), widely known as CANDU, are in operation in Argentina, Canada, China, India, Pakistan, Republic of Korea and Romania and account for about 6% of the world's nuclear electricity production. The CANDU reactor and its fuel have several unique features, like horizontal calandria and coolant tubes, on-power fuel loading, thin-walled collapsible clad coated with graphite on the inner surface, very high density (>96%TD) natural uranium oxide fuel and amenability to slightly enriched uranium oxide, mixed uranium plutonium oxide (MOX), mixed thorium plutonium oxide, mixed thorium uranium (U-233) oxide and inert matrix fuels. Several Technical Working Groups (TWG) of IAEA periodically discuss and review CANDU reactors, its fuel and fuel cycle options. These include TWGs on water-cooled nuclear power reactor Fuel Performance and Technology (TWGFPT), on Nuclear Fuel Cycle Options and spent fuel management (TWGNFCO) and on Heavy Water Reactors (TWGHWR). In addition, IAEA-INPRO project also covers Advanced CANDU Reactors (ACR) and DUPIC fuel cycles. The present paper summarises the Agency's activities in CANDU fuel and fuel cycle, highlighting the progress during the last two years. In the past we saw HWR and LWR technologies and fuel cycles separate, but nowadays their interaction is obviously growing, and their mutual influence may have a synergetic character if we look at the world nuclear fuel cycle as at an integrated system where the both are important elements in line with fast neutron, gas cooled and other advanced reactors. As an international organization the IAEA considers this challenge and makes concrete steps to tackle it for the benefit of all Member States. (author)

Trends and Developments for Fast Neutron Reactors and Related Fuel Cycles

International Nuclear Information System (INIS)

Carré, Frank

2013-01-01

• FR13 – A unique and dedicated framework to share updates on national programs of Fast Reactor developments, projects of new builds and plans for the future: - Near term projects of sodium and lead-alloy Fast Reactors; - Gen-IV visions of sodium-cooled and alternative types of Fast Neutron Reactors (GFR, LFR…). • FR13 – A special emphasis put on Fast Reactor Safety, Sustainability of nuclear fuel cycle and Young Generation perspective. • FR13 – A catalyst for further collaborations and alliances: - To share visions of goals and advisable options for future Fast Reactors and Nuclear Fuel Cycle; - To share cost of R&D and large demonstrations (safety, security, recycling); - To progress towards harmonized international standards; - To integrate national projects into a consistent international roadmap

BmCyclin B and BmCyclin B3 are required for cell cycle progression in the silkworm, Bombyx mori.

Science.gov (United States)

Pan, Minhui; Hong, Kaili; Chen, Xiangyun; Pan, Chun; Chen, Xuemei; Kuang, Xiuxiu; Lu, Cheng

2013-04-01

Cyclin B is an important regulator of the cell cycle G2 to M phase transition. The silkworm genomic database shows that there are two Cyclin B genes in the silkworm (Bombyx mori), BmCyclin B and BmCyclin B3. Using silkworm EST data, the cyclin B3 (EU074796) gene was cloned. Its complete cDNA was 1665 bp with an ORF of 1536 bp derived from seven exons and six introns. The BmCyclin B3 gene encodes 511 amino acids, and the predicted molecular weight is 57.8 kD with an isoelectric point of 9.18. The protein contains one protein damage box and two cyclin boxes. RNA interference-mediated reduction of BmCyclin B and BmCyclin B3 expression induced cell cycle arrest in G2 or M phase in BmN-SWU1 cells, thus inhibiting cell proliferation. These results suggest that BmCyclin B and BmCyclin B3 are necessary for completing the cell cycle in silkworm cells.

Tributyltin induces G2/M cell cycle arrest via NAD(+)-dependent isocitrate dehydrogenase in human embryonic carcinoma cells.

Science.gov (United States)

Asanagi, Miki; Yamada, Shigeru; Hirata, Naoya; Itagaki, Hiroshi; Kotake, Yaichiro; Sekino, Yuko; Kanda, Yasunari

2016-04-01

Organotin compounds, such as tributyltin (TBT), are well-known endocrine-disrupting chemicals (EDCs). We have recently reported that TBT induces growth arrest in the human embryonic carcinoma cell line NT2/D1 at nanomolar levels by inhibiting NAD(+)-dependent isocitrate dehydrogenase (NAD-IDH), which catalyzes the irreversible conversion of isocitrate to α-ketoglutarate. However, the molecular mechanisms by which NAD-IDH mediates TBT toxicity remain unclear. In the present study, we examined whether TBT at nanomolar levels affects cell cycle progression in NT2/D1 cells. Propidium iodide staining revealed that TBT reduced the ratio of cells in the G1 phase and increased the ratio of cells in the G2/M phase. TBT also reduced cell division cycle 25C (cdc25C) and cyclin B1, which are key regulators of G2/M progression. Furthermore, apigenin, an inhibitor of NAD-IDH, mimicked the effects of TBT. The G2/M arrest induced by TBT was abolished by NAD-IDHα knockdown. Treatment with a cell-permeable α-ketoglutarate analogue recovered the effect of TBT, suggesting the involvement of NAD-IDH. Taken together, our data suggest that TBT at nanomolar levels induced G2/M cell cycle arrest via NAD-IDH in NT2/D1 cells. Thus, cell cycle analysis in embryonic cells could be used to assess cytotoxicity associated with nanomolar level exposure of EDCs.

Current Progress of Si/Graphene Nanocomposites for Lithium-Ion Batteries

Directory of Open Access Journals (Sweden)

Yinjie Cen

2018-03-01

Full Text Available The demand for high performance lithium-ion batteries (LIBs is increasing due to widespread use of portable devices and electric vehicles. Silicon (Si is one of the most attractive candidate anode materials for next generation LIBs. However, the high-volume change (>300% during lithium ion alloying/de-alloying leads to poor cycle life. When Si is used as the anode, conductive carbon is needed to provide the necessary conductivity. However, the traditional carbon coating method could not overcome the challenges of pulverization and unstable Solid Electrolyte Interphase (SEI layer during long-term cycling. Since 2010, Si/Graphene composites have been vigorously studied in hopes of providing a material with better cycling performance. This paper reviews current progress of Si/Graphene nanocomposites in LIBs. Different fabrication methods have been studied to synthesize Si/Graphene nanocomposites with promising electrochemical performances. Graphene plays a key enabling role in Si/Graphene anodes. However, the desired properties of graphene for this application have not been systematically studied and understood. Further systematic investigation of the desired graphene properties is suggested to better control the Si/Graphene anode performance.

Effect of biogenic carbon inventory on the life cycle assessment of bioenergy: challenges to the neutrality assumption

NARCIS (Netherlands)

Wiloso, E.I.; Heijungs, R.; Huppes, G.; Fang, K.

2016-01-01

Biogenic carbon is defined as carbon contained in biomass that is accumulated during plant growth. In spite of the considerable progress towards the inventory of biogenic carbon in the life cycle assessment (LCA) of bioenergy in policy guidelines, many scientific articles tend to give no

The Role of Isocitrate Lyase (ICL1) in the Metabolic Adaptation of Candida albicans Biofilms

Science.gov (United States)