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Sample records for nf-e2 overexpression delays

  1. Knockdown of NF-E2-related factor 2 inhibits the proliferation and growth of U251MG human glioma cells in a mouse xenograft model.

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    Ji, Xiang-Jun; Chen, Sui-Hua; Zhu, Lin; Pan, Hao; Zhou, Yuan; Li, Wei; You, Wan-Chun; Gao, Chao-Chao; Zhu, Jian-Hong; Jiang, Kuan; Wang, Han-Dong

    2013-07-01

    NF-E2-related factor 2 (Nrf2) is a pivotal transcription factor of cellular responses to oxidative stress and recent evidence suggests that Nrf2 plays an important role in cancer pathobiology. However, the underlying mechanism has yet to be elucidated, particularly in glioma. In the present study, we investigated the role of Nrf2 in the clinical prognosis, cell proliferation and tumor growth of human glioblastoma multiforme (GBM). We detected overexpression of Nrf2 protein levels in GBM compared to normal brain tissues. Notably, higher protein levels of Nrf2 were significantly associated with poorer overall survival and 1-year survival for GBM patients. Furthermore, we constructed the plasmid Si-Nrf2 and transduced it into U251MG cells to downregulate the expression of Nrf2 and established stable Nrf2 knockdown cells. The downregulation of Nrf2 suppressed cell proliferation in vitro and tumor growth in mouse xenograft models. We performed immunohistochemistry staining to detect the protein levels of Nrf2, Ki-67, caspase-3 and CD31 in the xenograft tumors and found that the expression levels of Nrf2 and Ki-67 were much lower in the Si-Nrf2 group compared to the Si-control group. In addition, the number of caspase-3-positive cells was significantly increased in the Si-Nrf2 group. By analysis of microvessel density (MVD) assessed by CD31, the MVD value in the Si-Nrf2 group decreased significantly compared to the Si-control group. These findings indicate that the knockdown of Nrf2 may suppress tumor growth by inhibiting cell proliferation, increasing cell apoptosis and inhibiting angiogenesis. These results highlight the potential of Nrf2 as a candidate molecular target to control GBM cell proliferation and tumor growth.

  2. YUCCA6 over-expression demonstrates auxin function in delaying leaf senescence in Arabidopsis thaliana

    KAUST Repository

    Kim, Jeong Im

    2011-04-21

    The Arabidopsis thaliana YUCCA family of flavin monooxygenase proteins catalyses a rate-limiting step in de novo auxin biosynthesis. A YUCCA6 activation mutant, yuc6-1D, has been shown to contain an elevated free IAA level and to display typical high-auxin phenotypes. It is reported here that Arabidopsis plants over-expressing YUCCA6, such as the yuc6-1D activation mutant and 35S:YUC6 transgenic plants, displayed dramatic longevity. In addition, plants over-expressing YUCCA6 exhibited classical, delayed dark-induced and hormone-induced senescence in assays using detached rosette leaves. However, plants over-expressing an allele of YUCCA6, that carries mutations in the NADPH cofactor binding site, exhibited neither delayed leaf senescence phenotypes nor phenotypes typical of auxin overproduction. When the level of free IAA was reduced in yuc6-1D by conjugation to lysine, yuc6-1D leaves senesced at a rate similar to the wild-type leaves. Dark-induced senescence in detached leaves was accompanied by a decrease in their free IAA content, by the reduced expression of auxin biosynthesis enzymes such as YUCCA1 and YUCCA6 that increase cellular free IAA levels, and by the increased expression of auxin-conjugating enzymes encoded by the GH3 genes that reduce the cellular free auxin levels. Reduced transcript abundances of SAG12, NAC1, and NAC6 during senescence in yuc6-1D compared with the wild type suggested that auxin delays senescence by directly or indirectly regulating the expression of senescence-associated genes. 2011 The Author(s).

  3. Smad6/Smurf1 overexpression in cartilage delays chondrocyte hypertrophy and causes dwarfism with osteopenia

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    Horiki, Mitsuru; Imamura, Takeshi; Okamoto, Mina; Hayashi, Makoto; Murai, Junko; Myoui, Akira; Ochi, Takahiro; Miyazono, Kohei; Yoshikawa, Hideki; Tsumaki, Noriyuki

    2004-01-01

    Biochemical experiments have shown that Smad6 and Smad ubiquitin regulatory factor 1 (Smurf1) block the signal transduction of bone morphogenetic proteins (BMPs). However, their in vivo functions are largely unknown. Here, we generated transgenic mice overexpressing Smad6 in chondrocytes. Smad6 transgenic mice showed postnatal dwarfism with osteopenia and inhibition of Smad1/5/8 phosphorylation in chondrocytes. Endochondral ossification during development in these mice was associated with almost normal chondrocyte proliferation, significantly delayed chondrocyte hypertrophy, and thin trabecular bone. The reduced population of hypertrophic chondrocytes after birth seemed to be related to impaired bone growth and formation. Organ culture of cartilage rudiments showed that chondrocyte hypertrophy induced by BMP2 was inhibited in cartilage prepared from Smad6 transgenic mice. We then generated transgenic mice overexpressing Smurf1 in chondrocytes. Abnormalities were undetectable in Smurf1 transgenic mice. Mating Smad6 and Smurf1 transgenic mice produced double-transgenic pups with more delayed endochondral ossification than Smad6 transgenic mice. These results provided evidence that Smurf1 supports Smad6 function in vivo. PMID:15123739

  4. Anti-oxidative stress regulator NF-E2-related factor 2 mediates the adaptive induction of antioxidant and detoxifying enzymes by lipid peroxidation metabolite 4-hydroxynonenal

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    Huang Ying

    2012-11-01

    Full Text Available Abstract Background NF-E2-related factor 2 (NRF2 regulates a battery of antioxidative and phase II drug metabolizing/detoxifying genes through binding to the antioxidant response elements (ARE. NRF2-ARE signaling plays a central role in protecting cells from a wide spectrum of reactive toxic species including reactive oxygen/nitrogen species (RONS. 4-hydroxylnonenal (4-HNE is a major end product from lipid peroxidation of omega-6 polyunsaturated fatty acids (PUFA induced by oxidative stress, and it is highly reactive to nucleophilic sites in DNA and proteins, causing cytotoxicity and genotoxicity. In this study, we examined the role of NRF2 in regulating the 4-HNE induced gene expression of antioxidant and detoxifying enzymes. Results When HeLa cells were treated with 4-HNE, NRF2 rapidly transloated into the nucleus, as determined by the distribution of NRF2 tagged with the enhanced green fluorescent protein (EGFP and increased NRF2 protein in the nuclear fraction. Transcriptional activity of ARE-luciferase was significantly induced by 0.01-10 μM of 4-HNE in a dose-dependent manner, and the induction could be blocked by pretreatment with glutathione (GSH. 4-HNE induced transcriptional expression of glutathione S-transferase (GST A4, aldoketone reductase (AKR 1C1 and heme oxygenase-1 (HO-1, and the induction was attenuated by knocking down NRF2 using small interfering RNA. Conclusions NRF2 is critical in mediating 4-HNE induced expression of antioxidant and detoxifying genes. This may account for one of the major cellular defense mechanisms against reactive metabolites of lipids peroxidation induced by oxidative stress and protect cells from cytotoxicity.

  5. Overexpression of persimmon DkXTH1 enhanced tolerance to abiotic stress and delayed fruit softening in transgenic plants.

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    Han, Ye; Han, Shoukun; Ban, Qiuyan; He, Yiheng; Jin, Mijing; Rao, Jingping

    2017-04-01

    DkXTH1 promoted cell elongation and more strength to maintain structural integrity by involving in cell wall assembly, thus enhanced tolerance to abiotic stress with broader phenotype in transgenic plants. Xyloglucan endotransglucosylase/hydrolase (XTH) is thought to play a key role in cell wall modifications by cleaving and re-joining xyloglucan, and participates in the diverse physiological processes. DkXTH1 was found to peak in immature expanding persimmon fruit, and its higher expression level exhibited along with firmer fruit during storage. In the present study, transgenic Arabidopsis and tomato plants were generated with DkXTH1 constitutively expressed. Overexpression of DkXTH1 enhanced tolerance to salt, ABA and drought stresses in transgenic Arabidopsis plants with respect to root and leaf growth, and survival. Transgenic tomatoes collected at the mature green stage, presented delayed fruit softening coupled with postponed color change, a later and lower ethylene peak, and higher firmness in comparison with the wild-type tomatoes during storage. Furthermore, broader leaves and tomato fruit with larger diameter were gained in transgenic Arabidopsis and tomato, respectively. Most importantly, transgenic plants exhibited more large and irregular cells with higher density of cell wall and intercellular spaces, resulting from the overactivity of XET enzymes involving in cell wall assembly. We suggest that DkXTH1 expression resulted in cells with more strength and thickness to maintain structural integrity, and thus enhanced tolerance to abiotic stress and delayed fruit softening in transgenic plants.

  6. Overexpression of a novel MADS-box gene SlFYFL delays senescence, fruit ripening and abscission in tomato

    Science.gov (United States)

    Xie, Qiaoli; Hu, Zongli; Zhu, Zhiguo; Dong, Tingting; Zhao, Zhiping; Cui, Baolu; Chen, Guoping

    2014-03-01

    MADS-domain proteins are important transcription factors involved in many biological processes of plants. In our study, a tomato MADS-box gene, SlFYFL, was isolated. SlFYFL is expressed in all tissues of tomato and significantly higher in mature leave, fruit of different stages, AZ (abscission zone) and sepal. Delayed leaf senescence and fruit ripening, increased storability and longer sepals were observed in 35S:FYFL tomato. The accumulation of carotenoid was reduced, and ethylene content, ethylene biosynthetic and responsive genes were down-regulated in 35S:FYFL fruits. Abscission zone (AZ) did not form normally and abscission zone development related genes were declined in AZs of 35S:FYFL plants. Yeast two-hybrid assay revealed that SlFYFL protein could interact with SlMADS-RIN, SlMADS1 and SlJOINTLESS, respectively. These results suggest that overexpression of SlFYFL regulate fruit ripening and development of AZ via interactions with the ripening and abscission zone-related MADS box proteins.

  7. Overexpression of eIF5 or its protein mimic 5MP perturbs eIF2 function and induces ATF4 translation through delayed re-initiation.

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    Kozel, Caitlin; Thompson, Brytteny; Hustak, Samantha; Moore, Chelsea; Nakashima, Akio; Singh, Chingakham Ranjit; Reid, Megan; Cox, Christian; Papadopoulos, Evangelos; Luna, Rafael E; Anderson, Abbey; Tagami, Hideaki; Hiraishi, Hiroyuki; Slone, Emily Archer; Yoshino, Ken-Ichi; Asano, Masayo; Gillaspie, Sarah; Nietfeld, Jerome; Perchellet, Jean-Pierre; Rothenburg, Stefan; Masai, Hisao; Wagner, Gerhard; Beeser, Alexander; Kikkawa, Ushio; Fleming, Sherry D; Asano, Katsura

    2016-10-14

    ATF4 is a pro-oncogenic transcription factor whose translation is activated by eIF2 phosphorylation through delayed re-initiation involving two uORFs in the mRNA leader. However, in yeast, the effect of eIF2 phosphorylation can be mimicked by eIF5 overexpression, which turns eIF5 into translational inhibitor, thereby promoting translation of GCN4, the yeast ATF4 equivalent. Furthermore, regulatory protein termed eIF5-mimic protein (5MP) can bind eIF2 and inhibit general translation. Here, we show that 5MP1 overexpression in human cells leads to strong formation of 5MP1:eIF2 complex, nearly comparable to that of eIF5:eIF2 complex produced by eIF5 overexpression. Overexpression of eIF5, 5MP1 and 5MP2, the second human paralog, promotes ATF4 expression in certain types of human cells including fibrosarcoma. 5MP overexpression also induces ATF4 expression in Drosophila The knockdown of 5MP1 in fibrosarcoma attenuates ATF4 expression and its tumor formation on nude mice. Since 5MP2 is overproduced in salivary mucoepidermoid carcinoma, we propose that overexpression of eIF5 and 5MP induces translation of ATF4 and potentially other genes with uORFs in their mRNA leaders through delayed re-initiation, thereby enhancing the survival of normal and cancer cells under stress conditions. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. Association between the NF-E2 Related Factor 2 Gene Polymorphism and Oxidative Stress, Anti-Oxidative Status, and Newly-Diagnosed Type 2 Diabetes Mellitus in a Chinese Population

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    Xia Wang

    2015-07-01

    Full Text Available Oxidative stress is a major risk factor in the onset and progression of type 2 diabetes mellitus (T2DM. NF-E2 related factor 2 (NRF2 is a pivotal transcription factor in oxidative stress related illnesses. This study included 2174 subjects with 879 cases of newly-diagnosed T2DM and 1295 healthy controls. Compared to individuals with the CC genotype, those with the AA genotype had lower total anti-oxidative capacity, superoxide dismutase, catalase, glutathione, glutathione peroxidase activity; and lower homeostasis model assessment of β-cell function index. Those with the AA genotype also had a higher malondialdehyde concentration and homeostasis model assessment of insulin resistance index values. The frequency of allele A was significantly higher in T2DM subjects (29.4%, compared to control subjects (26.1%; p = 0.019. Individuals with the AA genotype had a significantly higher risk of developing T2DM (OR 1.56; 95% CI 1.11, 2.20; p = 0.011, relative to those with the CC genotype, even after adjusting for known T2DM risk factors. Our results suggest that the NRF2 rs6721961 polymorphism was significantly associated with oxidative stress, anti-oxidative status, and risk of newly-diagnosed T2DM. This polymorphism may also contribute to impaired insulin secretory capacity and increased insulin resistance in a Chinese population.

  9. Transcriptomic changes reveal gene networks responding to the overexpression of a blueberry DWARF AND DELAYED FLOWERING 1 gene in transgenic blueberry plants.

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    Song, Guo-Qing; Gao, Xuan

    2017-06-19

    Constitutive expression of the CBF/DREB1 for increasing freezing tolerance in woody plants is often associated with other phenotypic changes including dwarf plant and delayed flowering. These phenotypic changes have been observed when Arabidopsis DWARF AND DELAYED FLOWERING 1 (DDF1) was overexpressed in A. thaliana plants. To date, the DDF1 orthologues have not been studied in woody plants. The aim of this study is to investigate transcriptomic responses to the overexpression of blueberry (Vaccinium corymbosum) DDF1 (herein, VcDDF1-OX). The VcDDF1-OX resulted in enhanced freezing tolerance in tetraploid blueberry plants and did not result in significant changes in plant size, chilling requirement, and flowering time. Comparative transcriptome analysis of transgenic 'Legacy-VcDDF1-OX' plants containing an overexpressed VcDDF1 with non-transgenic highbush blueberry 'Legacy' plants revealed the VcDDF1-OX derived differentially expressed (DE) genes and transcripts in the pathways of cold-response, plant flowering, DELLA proteins, and plant phytohormones. The increase in freezing tolerance was associated to the expression of cold-regulated genes (CORs) and the ethylene pathway genes. The unchanged plant size, dormancy and flowering were due to the minimal effect of the VcDDF1-OX on the expression of DELLA proteins, flowering pathway genes, and the other phytohormone genes related to plant growth and development. The DE genes in auxin and cytokinin pathways suggest that the VcDDF1-OX has also altered plant tolerance to drought and high salinity. A DDF1 orthologue in blueberry functioned differently from the DDF1 reported in Arabidopsis. The overexpression of VcDDF1 or its orthologues is a new approach to increase freezing tolerance of deciduous woody plant species with no obvious effect on plant size and plant flowering time.

  10. Parvalbumin overexpression alters immune-mediated increases in intracellular calcium, and delays disease onset in a transgenic model of familial amyotrophic lateral sclerosis

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    Beers, D. R.; Ho, B. K.; Siklos, L.; Alexianu, M. E.; Mosier, D. R.; Mohamed, A. H.; Otsuka, Y.; Kozovska, M. E.; McAlhany, R. E.; Smith, R. G.; hide

    2001-01-01

    Intracellular calcium is increased in vulnerable spinal motoneurons in immune-mediated as well as transgenic models of amyotrophic lateral sclerosis (ALS). To determine whether intracellular calcium levels are influenced by the calcium-binding protein parvalbumin, we developed transgenic mice overexpressing parvalbumin in spinal motoneurons. ALS immunoglobulins increased intracellular calcium and spontaneous transmitter release at motoneuron terminals in control animals, but not in parvalbumin overexpressing transgenic mice. Parvalbumin transgenic mice interbred with mutant SOD1 (mSOD1) transgenic mice, an animal model of familial ALS, had significantly reduced motoneuron loss, and had delayed disease onset (17%) and prolonged survival (11%) when compared with mice with only the mSOD1 transgene. These results affirm the importance of the calcium binding protein parvalbumin in altering calcium homeostasis in motoneurons. The increased motoneuron parvalbumin can significantly attenuate the immune-mediated increases in calcium and to a lesser extent compensate for the mSOD1-mediated 'toxic-gain-of-function' in transgenic mice.

  11. The overexpression of insect endogenous small RNAs in transgenic rice inhibits growth and delays pupation of striped stem borer (Chilo suppressalis).

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    Jiang, Shan; Wu, Hao; Liu, Haoju; Zheng, Jie; Lin, Yongjun; Chen, Hao

    2017-07-01

    The striped stem borer (SSB), Chilo suppressalis Walker, is a major rice insect pest worldwide. RNA interference (RNAi) has become a promising strategy for developing insect-resistant crops. In a previous study, five double-stranded RNAs (dsRNAs) targeting important SSB housekeeping genes were overexpressed in rice, but none of the acquired dsRNA-transgenic rice plants showed significant effects on SSB. Thirteen selected SSB endogenous small RNAs, predicted as SSB novel microRNAs (miRNAs), were overexpressed in rice using artificial miRNA (amiRNA) expression technology. Feeding tests showed that two out of 13 selected SSB novel miRNAs caused significant growth inhibition for feeding SSB larvae based on transgenic rice expression. Pupation was delayed 4 days when SSB larvae consecutively fed on transgenic rice expressing the SSB novel miRNA candidate csu-novel-miR15 (csu-15 rice). Gene expression analysis confirmed that the expression levels of at least six SSB unigenes significantly changed (i.e., were up- or down-regulated) after feeding on csu-15 rice. Our research demonstrated a novel RNAi strategy using SSB endogenous small RNAs to develop RNAi crops for pest management; this strategy is different from the common RNAi resulting from transgenic dsRNAs or amiRNAs targeting certain insect endogenous genes. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  12. Overexpression of PvPin1, a Bamboo Homolog of PIN1-Type Parvulin 1, Delays Flowering Time in Transgenic Arabidopsis and Rice

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    Zhigang Zheng

    2017-09-01

    Full Text Available Because of the long and unpredictable flowering period in bamboo, the molecular mechanism of bamboo flowering is unclear. Recent study showed that Arabidopsis PIN1-type parvulin 1 (Pin1At is an important floral activator and regulates floral transition by facilitating the cis/trans isomerization of the phosphorylated Ser/Thr residues preceding proline motifs in suppressor of overexpression of CO 1 (SOC1 and agamous-like 24 (AGL24. Whether bamboo has a Pin1 homolog and whether it works in bamboo flowering are still unknown. In this study, we cloned PvPin1, a homolog of Pin1At, from Phyllostachys violascens (Bambusoideae. Bioinformatics analysis showed that PvPin1 is closely related to Pin1-like proteins in monocots. PvPin1 was widely expressed in all tested bamboo tissues, with the highest expression in young leaf and lowest in floral bud. Moreover, PvPin1 expression was high in leaves before bamboo flowering then declined during flower development. Overexpression of PvPin1 significantly delayed flowering time by downregulating SOC1 and AGL24 expression in Arabidopsis under greenhouse conditions and conferred a significantly late flowering phenotype by upregulating OsMADS56 in rice under field conditions. PvPin1 showed subcellular localization in both the nucleus and cytolemma. The 1500-bp sequence of the PvPin1 promoter was cloned, and cis-acting element prediction showed that ABRE and TGACG-motif elements, which responded to abscisic acid (ABA and methyl jasmonate (MeJA, respectively, were characteristic of P. violascens in comparison with Arabidopsis. On promoter activity analysis, exogenous ABA and MeJA could significantly inhibit PvPin1 expression. These findings suggested that PvPin1 may be a repressor in flowering, and its delay of flowering time could be regulated by ABA and MeJA in bamboo.

  13. Overexpression of PvPin1, a Bamboo Homolog of PIN1-Type Parvulin 1, Delays Flowering Time in Transgenic Arabidopsis and Rice.

    Science.gov (United States)

    Zheng, Zhigang; Yang, Xiaoming; Fu, Yaping; Zhu, Longfei; Wei, Hantian; Lin, Xinchun

    2017-01-01

    Because of the long and unpredictable flowering period in bamboo, the molecular mechanism of bamboo flowering is unclear. Recent study showed that Arabidopsis PIN1-type parvulin 1 (Pin1At) is an important floral activator and regulates floral transition by facilitating the cis/trans isomerization of the phosphorylated Ser/Thr residues preceding proline motifs in suppressor of overexpression of CO 1 (SOC1) and agamous-like 24 (AGL24). Whether bamboo has a Pin1 homolog and whether it works in bamboo flowering are still unknown. In this study, we cloned PvPin1 , a homolog of Pin1At , from Phyllostachys violascens (Bambusoideae). Bioinformatics analysis showed that PvPin1 is closely related to Pin1-like proteins in monocots. PvPin1 was widely expressed in all tested bamboo tissues, with the highest expression in young leaf and lowest in floral bud. Moreover, PvPin1 expression was high in leaves before bamboo flowering then declined during flower development. Overexpression of PvPin1 significantly delayed flowering time by downregulating SOC1 and AGL24 expression in Arabidopsis under greenhouse conditions and conferred a significantly late flowering phenotype by upregulating OsMADS56 in rice under field conditions. PvPin1 showed subcellular localization in both the nucleus and cytolemma. The 1500-bp sequence of the PvPin1 promoter was cloned, and cis -acting element prediction showed that ABRE and TGACG-motif elements, which responded to abscisic acid (ABA) and methyl jasmonate (MeJA), respectively, were characteristic of P. violascens in comparison with Arabidopsis . On promoter activity analysis, exogenous ABA and MeJA could significantly inhibit PvPin1 expression. These findings suggested that PvPin1 may be a repressor in flowering, and its delay of flowering time could be regulated by ABA and MeJA in bamboo.

  14. Overexpression of Nitrate Reductase in Tobacco Delays Drought-Induced Decreases in Nitrate Reductase Activity and mRNA1

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    Ferrario-Méry, Sylvie; Valadier, Marie-Hélène; Foyer, Christine H.

    1998-01-01

    Transformed (cauliflower mosaic virus 35S promoter [35S]) tobacco (Nicotiana plumbaginifolia L.) plants constitutively expressing nitrate reductase (NR) and untransformed controls were subjected to drought for 5 d. Drought-induced changes in biomass accumulation and photosynthesis were comparable in both lines of plants. After 4 d of water deprivation, a large increase in the ratio of shoot dry weight to fresh weight was observed, together with a decrease in the rate of photosynthetic CO2 assimilation. Foliar sucrose increased in both lines during water stress, but hexoses increased only in leaves from untransformed controls. Foliar NO3− decreased rapidly in both lines and was halved within 2 d of the onset of water deprivation. Total foliar amino acids decreased in leaves of both lines following water deprivation. After 4 d of water deprivation no NR activity could be detected in leaves of untransformed plants, whereas about 50% of the original activity remained in the leaves of the 35S-NR transformants. NR mRNA was much more stable than NR activity. NR mRNA abundance increased in the leaves of the 35S-NR plants and remained constant in controls for the first 3 d of drought. On the 4th d, however, NR mRNA suddenly decreased in both lines. Rehydration at d 3 caused rapid recovery (within 24 h) of 35S-NR transcripts, but no recovery was observed in the controls. The phosphorylation state of the protein was unchanged by long-term drought. There was a strong correlation between maximal extractable NR activity and ambient photosynthesis in both lines. We conclude that drought first causes increased NR protein turnover and then accelerates NR mRNA turnover. Constitutive NR expression temporarily delayed drought-induced losses in NR activity. 35S-NR expression may therefore allow more rapid recovery of N assimilation following short-term water deficit. PMID:9576799

  15. Cartilage-Specific and Cre-Dependent Nkx3.2 Overexpression In Vivo Causes Skeletal Dwarfism by Delaying Cartilage Hypertrophy.

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    Jeong, Da-Un; Choi, Je-Yong; Kim, Dae-Won

    2017-01-01

    Nkx3.2, the vertebrate homologue of Drosophila bagpipe, has been implicated as playing a role in chondrogenic differentiation. In brief, Nkx3.2 is initially expressed in chondrocyte precursor cells and later during cartilage maturation, its expression is diminished in hypertrophic chondrocytes. In addition to Nkx3.2 expression analyses, previous studies using ex vivo chick embryo cultures and in vitro cell cultures have suggested that Nkx3.2 can suppress chondrocyte hypertrophy. However, it has never been demonstrated that Nkx3.2 functions in regulating chondrocyte hypertrophy during cartilage development in vivo. Here, we show that cartilage-specific and Cre-dependent Nkx3.2 overexpression in mice results in significant postnatal dwarfism in endochondral skeletons, while intramembranous bones remain unaltered. Further, we observed significant delays in cartilage hypertrophy in conditional transgenic ciTg-Nkx3.2 mice. Together, these findings confirm that Nkx3.2 is capable of controlling hypertrophic maturation of cartilage in vivo, and this regulation plays a significant role in endochondral ossification and longitudinal bone growth. J. Cell. Physiol. 232: 78-90, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Overexpression of MpCYS4, a phytocystatin gene from Malus prunifolia (Willd.) Borkh., delays natural and stress-induced leaf senescence in apple.

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    Tan, Yanxiao; Yang, Yingli; Li, Chao; Liang, Bowen; Li, Mingjun; Ma, Fengwang

    2017-06-01

    Phytocystatins are a well-characterized class of naturally occurring protease inhibitors that prevent the catalysis of papain-like cysteine proteases. The action of cystatins in stress tolerance has been studied intensively, but relatively little is known about their functions in plants during leaf senescence. Here, we examined the potential roles of the apple cystatin, MpCYS4, in leaf photosynthesis as well as the concentrations and composition of leaf proteins when plants encounter natural or stress-induced senescence. Overexpression of this gene in apple rootstock M26 effectively slowed the senescence-related declines in photosynthetic activity and chlorophyll concentrations and prevented the action of cysteine proteinases during the process of degrading proteins (e.g., Rubisco) in senescing leaves. Moreover, MpCYS4 alleviated the associated oxidative damage and enhanced the capacity of plants to eliminate reactive oxygen species by activating antioxidant enzymes such as ascorbate peroxidase, peroxidase, and catalase. Consequently, plant cells were protected against damage from free radicals during leaf senescence. Based on these results, we conclude that MpCYS4 functions in delaying natural and stress-induced senescence of apple leaves. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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

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    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.

  18. Overexpression of pig selenoprotein S blocks OTA-induced promotion of PCV2 replication by inhibiting oxidative stress and p38 phosphorylation in PK15 cells

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    Gan, Fang; Hu, Zhihua; Huang, Yu; Xue, Hongxia; Huang, Da; Qian, Gang; Hu, Junfa; Chen, Xingxiang; Wang, Tian; Huang, Kehe

    2016-01-01

    Porcine circovirus type 2 (PCV2) is the primary cause of porcine circovirus disease, and ochratoxin A (OTA)-induced oxidative stress promotes PCV2 replication. In humans, selenoprotein S (SelS) has antioxidant ability, but it is unclear whether SelS affects viral infection. Here, we stably transfected PK15 cells with pig pCDNA3.1-SelS to overexpress SelS. Selenium (Se) at 2 or 4 μM and SelS overexpression blocked the OTA-induced increases of PCV2 DNA copy number and infected cell numbers. SelS overexpression also increased glutathione (GSH), NF-E2-related factor 2 (Nrf2) mRNA, and γ-glutamyl-cysteine synthetase mRNA levels; decreased reactive oxygen species (ROS) levels; and inhibited p38 phosphorylation in PCV2-infected PK15 cells, regardless of OTA treatment. Buthionine sulfoximine reversed all of the above SelS-induced changes. siRNA-mediated SelS knockdown decreased Nrf2 mRNA and GSH levels, increased ROS levels, and promoted PCV2 replication in OTA-treated PK15 cells. These data indicate that pig SelS blocks OTA-induced promotion of PCV2 replication by inhibiting the oxidative stress and p38 phosphorylation in PK15 cells. PMID:26943035

  19. Quantitative nature of overexpression experiments

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    Moriya, Hisao

    2015-01-01

    Overexpression experiments are sometimes considered as qualitative experiments designed to identify novel proteins and study their function. However, in order to draw conclusions regarding protein overexpression through association analyses using large-scale biological data sets, we need to recognize the quantitative nature of overexpression experiments. Here I discuss the quantitative features of two different types of overexpression experiment: absolute and relative. I also introduce the four primary mechanisms involved in growth defects caused by protein overexpression: resource overload, stoichiometric imbalance, promiscuous interactions, and pathway modulation associated with the degree of overexpression. PMID:26543202

  20. Delayed fission

    Energy Technology Data Exchange (ETDEWEB)

    Hatsukawa, Yuichi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1997-07-01

    Delayed fission is a nuclear decay process that couples {beta} decay and fission. In the delayed fission process, a parent nucleus undergoes {beta} decay and thereby populates excited states in the daughter. If these states are of energies comparable to or greater than the fission barrier of the daughter, then fission may compete with other decay modes of the excited states in the daughter. In this paper, mechanism and some experiments of the delayed fission will be discussed. (author)

  1. Delayed Ejaculation

    Science.gov (United States)

    ... cases, it is due to a combination of physical and psychological concerns. Psychological causes of delayed ejaculation include: Depression, anxiety or other mental health conditions Relationship problems due to stress, poor communication ...

  2. Delayed growth

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    ... Slow rate of growth; Retarded growth and development; Growth delay Images Toddler development References Cooke DW, Divall SA, Radovick S. Normal and aberrant growth in children. In: Melmed S, Polonsky KS, Larsen PR, ...

  3. Developmental delay

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    Nutrition support is essential for the care of the child with developmental delay. After a thorough evaluation, an individualized intervention plan that accounts for the child’s nutrition status, feeding ability, and medical condition may be determined. Nutrition assessments may be performed at leas...

  4. Delayed Puberty

    DEFF Research Database (Denmark)

    Kolby, Nanna; Busch, Alexander Siegfried; Juul, Anders

    2017-01-01

    . The underlying reasons for the large variation in the age at pubertal onset are not fully established; however, nutritional status and socioeconomic and environmental factors are known to be influencing, and a significant amount of influencing genetic factors have also been identified. The challenges...... optimal in discriminating especially CDGP from HH. Management of the delayed puberty depends on the etiology. For boys with CDGP an observational period will often reveal imminent puberty. If puberty is not progressing spontaneously, sex steroid replacement is effective in stimulating the development...

  5. Revolutionizing membrane protein overexpression in bacteria

    NARCIS (Netherlands)

    Schlegel, Susan; Klepsch, Mirjam; Gialama, Dimitra; Wickstrom, David; Slotboom, Dirk Jan; de Gier, Jan-Willem; Wickström, David

    The bacterium Escherichia coli is the most widely used expression host for overexpression trials of membrane proteins. Usually, different strains, culture conditions and expression regimes are screened for to identify the optimal overexpression strategy. However, yields are often not satisfactory,

  6. Gene Overexpression: Uses, Mechanisms, and Interpretation

    Science.gov (United States)

    2012-01-01

    The classical genetic approach for exploring biological pathways typically begins by identifying mutations that cause a phenotype of interest. Overexpression or misexpression of a wild-type gene product, however, can also cause mutant phenotypes, providing geneticists with an alternative yet powerful tool to identify pathway components that might remain undetected using traditional loss-of-function analysis. This review describes the history of overexpression, the mechanisms that are responsible for overexpression phenotypes, tests that begin to distinguish between those mechanisms, the varied ways in which overexpression is used, the methods and reagents available in several organisms, and the relevance of overexpression to human disease. PMID:22419077

  7. NUCKS overexpression in breast cancer

    Directory of Open Access Journals (Sweden)

    Kittas Christos

    2009-08-01

    Full Text Available Abstract Background NUCKS (Nuclear, Casein Kinase and Cyclin-dependent Kinase Substrate is a nuclear, DNA-binding and highly phosphorylated protein. A number of reports show that NUCKS is highly expressed on the level of mRNA in several human cancers, including breast cancer. In this work, NUCKS expression on both RNA and protein levels was studied in breast tissue biopsies consisted of invasive carcinomas, intraductal proliferative lesions, benign epithelial proliferations and fibroadenomas, as well as in primary cultures derived from the above biopsies. Specifically, in order to evaluate the level of NUCKS protein in correlation with the histopathological features of breast disease, immunohistochemistry was employed on paraffin sections of breast biopsies of the above types. In addition, NUCKS expression was studied by means of Reverse Transcription PCR (RT-PCR, real-time PCR (qRT-PCR and Western immunoblot analyses in the primary cell cultures developed from the same biopsies. Results The immunohistochemical Results showed intense NUCKS staining mostly in grade I and II breast carcinomas compared to normal tissues. Furthermore, NUCKS was moderate expressed in benign epithelial proliferations, such as adenosis and sclerosing adenosis, and highly expressed in intraductal lesions, specifically in ductal carcinomas in situ (DCIS. It is worth noting that all the fibroadenoma tissues examined were negative for NUCKS staining. RT-PCR and qRT-PCR showed an increase of NUCKS expression in cells derived from primary cultures of proliferative lesions and cancerous tissues compared to the ones derived from normal breast tissues and fibroadenomas. This increase was also confirmed by Western immunoblot analysis. Although NUCKS is a cell cycle related protein, its expression does not correlate with Ki67 expression, neither in tissue sections nor in primary cell cultures. Conclusion The results show overexpression of the NUCKS protein in a number of non

  8. Delayed puberty in girls

    Science.gov (United States)

    ... sexual development - girls; Pubertal delay - girls; Constitutional delayed puberty ... In most cases of delayed puberty, growth changes just begin later than usual, sometimes called a late bloomer. Once puberty begins, it progresses normally. This pattern runs ...

  9. Delayed Puberty (For Teens)

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Delayed Puberty KidsHealth / For Teens / Delayed Puberty What's in this ... wonder if there's anything wrong. What Is Delayed Puberty? Puberty is the time when your body grows ...

  10. Speech and Language Delay

    Science.gov (United States)

    ... OTC Relief for Diarrhea Home Diseases and Conditions Speech and Language Delay Condition Speech and Language Delay Share Print Table of Contents1. ... Treatment6. Everyday Life7. Questions8. Resources What is a speech and language delay? A speech and language delay ...

  11. In vivo overexpression of Emi1 promotes chromosome instability and tumorigenesis.

    Science.gov (United States)

    Vaidyanathan, S; Cato, K; Tang, L; Pavey, S; Haass, N K; Gabrielli, B G; Duijf, P H G

    2016-10-13

    Cell cycle genes are often aberrantly expressed in cancer, but how their misexpression drives tumorigenesis mostly remains unclear. From S phase to early mitosis, EMI1 (also known as FBXO5) inhibits the anaphase-promoting complex/cyclosome, which controls cell cycle progression through the sequential degradation of various substrates. By analyzing 7403 human tumor samples, we find that EMI1 overexpression is widespread in solid tumors but not in blood cancers. In solid cancers, EMI1 overexpression is a strong prognostic marker for poor patient outcome. To investigate causality, we generated a transgenic mouse model in which we overexpressed Emi1. Emi1-overexpressing animals develop a wide variety of solid tumors, in particular adenomas and carcinomas with inflammation and lymphocyte infiltration, but not blood cancers. These tumors are significantly larger and more penetrant, abundant, proliferative and metastatic than control tumors. In addition, they are highly aneuploid with tumor cells frequently being in early mitosis and showing mitotic abnormalities, including lagging and incorrectly segregating chromosomes. We further demonstrate in vitro that even though EMI1 overexpression may cause mitotic arrest and cell death, it also promotes chromosome instability (CIN) following delayed chromosome alignment and anaphase onset. In human solid tumors, EMI1 is co-expressed with many markers for CIN and EMI1 overexpression is a stronger marker for CIN than most well-established ones. The fact that Emi1 overexpression promotes CIN and the formation of solid cancers in vivo indicates that Emi1 overexpression actively drives solid tumorigenesis. These novel mechanistic insights have important clinical implications.

  12. Overexpression of Catalase Diminishes Oxidative Cysteine Modifications of Cardiac Proteins.

    Directory of Open Access Journals (Sweden)

    Chunxiang Yao

    Full Text Available Reactive protein cysteine thiolates are instrumental in redox regulation. Oxidants, such as hydrogen peroxide (H2O2, react with thiolates to form oxidative post-translational modifications, enabling physiological redox signaling. Cardiac disease and aging are associated with oxidative stress which can impair redox signaling by altering essential cysteine thiolates. We previously found that cardiac-specific overexpression of catalase (Cat, an enzyme that detoxifies excess H2O2, protected from oxidative stress and delayed cardiac aging in mice. Using redox proteomics and systems biology, we sought to identify the cysteines that could play a key role in cardiac disease and aging. With a 'Tandem Mass Tag' (TMT labeling strategy and mass spectrometry, we investigated differential reversible cysteine oxidation in the cardiac proteome of wild type and Cat transgenic (Tg mice. Reversible cysteine oxidation was measured as thiol occupancy, the ratio of total available versus reversibly oxidized cysteine thiols. Catalase overexpression globally decreased thiol occupancy by ≥1.3 fold in 82 proteins, including numerous mitochondrial and contractile proteins. Systems biology analysis assigned the majority of proteins with differentially modified thiols in Cat Tg mice to pathways of aging and cardiac disease, including cellular stress response, proteostasis, and apoptosis. In addition, Cat Tg mice exhibited diminished protein glutathione adducts and decreased H2O2 production from mitochondrial complex I and II, suggesting improved function of cardiac mitochondria. In conclusion, our data suggest that catalase may alleviate cardiac disease and aging by moderating global protein cysteine thiol oxidation.

  13. Disruption of Inhibitory Function in the Ts65Dn Mouse Hippocampus Through Overexpression of GIRK2

    Science.gov (United States)

    2007-10-24

    embryological and developmental or a result of later problems. Delays in prenatal growth of the Ts65Dn cerebral cortex and hippocampus due to longer...cultured from both DS patients and model animals are also reportedly more vulnerable to apoptosis (Sawa, 1999). A majority of research investigating cell...death in DS has been limited to several apoptosis -related genes, including those related to oxidative stress, and transcription factors overexpressed

  14. UAVs and Control Delays

    National Research Council Canada - National Science Library

    de Vries, S. C

    2005-01-01

    .... Delays of about 250-300 ms often lead to unacceptable airplane handling qualities. Techniques such as filtering and predictive displays may extend the range of acceptable delays up to about 400 ms...

  15. Delayed puberty in boys

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/007695.htm Delayed puberty in boys To use the sharing features on this page, please enable JavaScript. Delayed puberty in boys is when puberty does not begin ...

  16. Functional and gene expression analysis of hTERT overexpressed endothelial cells

    Directory of Open Access Journals (Sweden)

    Haruna Takano

    2008-09-01

    Full Text Available Haruna Takano1, Satoshi Murasawa1,2, Takayuki Asahara1,2,31Institute of Biomedical Research and Innovation, Kobe, Japan; 2RIKEN Center for Developmental Biology, Kobe 650-0047, Japan; 3Tokai University of School of Medicine, Tokai, JapanAbstract: Telomerase dysfunction contributes to cellular senescence. Recent advances indicate the importance of senescence in maintaining vascular cell function in vitro. Human telomerase reverse transcriptase (hTERT overexpression is thought to lead to resistance to apoptosis and oxidative stress. However, the mechanism in endothelial lineage cells is unclear. We tried to generate an immortal endothelial cell line from human umbilical vein endothelial cells using a no-virus system and examine the functional mechanisms of hTERT overexpressed endothelial cell senescence in vitro. High levels of hTERT genes and endothelial cell-specific markers were expressed during long-term culture. Also, angiogenic responses were observed in hTERT overexpressed endothelial cell. These cells showed a delay in senescence and appeared more resistant to stressed conditions. PI3K/Akt-related gene levels were enhanced in hTERT overexpressed endothelial cells. An up-regulated PI3K/Akt pathway caused by hTERT overexpression might contribute to anti-apoptosis and survival effects in endothelial lineage cells.Keywords: endothelial, telomerase, senescence, oxidative stress, anti-apoptosis, PI3K/Akt pathway

  17. Delayed Orgasm and Anorgasmia

    OpenAIRE

    Jenkins, Lawrence C.; Mulhall, John P.

    2015-01-01

    Delayed orgasm/anorgasmia defined as the persistent or recurrent difficulty, delay in, or absence of attaining orgasm after sufficient sexual stimulation, which causes personal distress. Delayed orgasm and anorgasmia are associated with significant sexual dissatisfaction. A focused medical history can shed light on the potential etiologies; which include: medications, penile sensation loss, endocrinopathies, penile hyperstimulation and psychological etiologies, amongst others. Unfortunately, ...

  18. Significance of Aurora B overexpression in hepatocellular carcinoma. Aurora B Overexpression in HCC

    International Nuclear Information System (INIS)

    Lin, Zhong-Zhe; Jeng, Yung-Ming; Hu, Fu-Chang; Pan, Hung-Wei; Tsao, Hsin-Wei; Lai, Po-Lin; Lee, Po-Huang; Cheng, Ann-Lii; Hsu, Hey-Chi

    2010-01-01

    To investigate the significance of Aurora B expression in hepatocellular carcinoma (HCC). The Aurora B and Aurora A mRNA level was measured in 160 HCCs and the paired nontumorous liver tissues by reverse transcription-polymerase chain reaction. Mutations of the p53 and β-catenin genes were analyzed in 134 and 150 tumors, respectively, by direct sequencing of exon 2 to exon 11 of p53 and exon 3 of β-catenin. Anticancer effects of AZD1152-HQPA, an Aurora B kinase selective inhibitor, were examined in Huh-7 and Hep3B cell lines. Aurora B was overexpressed in 98 (61%) of 160 HCCs and in all 7 HCC cell lines examined. The overexpression of Aurora B was associated with Aurora A overexpression (P = 0.0003) and p53 mutation (P = 0.002) and was inversely associated with β-catenin mutation (P = 0.002). Aurora B overexpression correlated with worse clinicopathologic characteristics. Multivariate analysis confirmed that Aurora B overexpression was an independent poor prognostic factor, despite its interaction with Aurora A overexpression and mutations of p53 and β-catenin. In Huh-7 and Hep3B cells, AZD1152-HQPA induced proliferation blockade, histone H3 (Ser10) dephosphorylation, cell cycle disturbance, and apoptosis. Aurora B overexpression is an independent molecular marker predicting tumor invasiveness and poor prognosis of HCC. Aurora B kinase selective inhibitors are potential therapeutic agents for HCC treatment

  19. Delayed orgasm and anorgasmia.

    Science.gov (United States)

    Jenkins, Lawrence C; Mulhall, John P

    2015-11-01

    Delayed orgasm/anorgasmia defined as the persistent or recurrent difficulty, delay in, or absence of attaining orgasm after sufficient sexual stimulation, which causes personal distress. Delayed orgasm and anorgasmia are associated with significant sexual dissatisfaction. A focused medical history can shed light on the potential etiologies, which include medications, penile sensation loss, endocrinopathies, penile hyperstimulation, and psychological etiologies. Unfortunately, there are no excellent pharmacotherapies for delayed orgasm/anorgasmia, and treatment revolves largely around addressing potential causative factors and psychotherapy. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  20. Hand1 overexpression inhibits medulloblastoma metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Asuthkar, Swapna; Guda, Maheedhara R. [Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61656 (United States); Martin, Sarah E. [Department of Pathology, University of Illinois College of Medicine at Peoria, Peoria, IL 61656 (United States); Antony, Reuben; Fernandez, Karen [Department of Pediatrics, University of Illinois College of Medicine at Peoria, Peoria, IL 61656 (United States); Lin, Julian [Department of Neurosurgery, University of Illinois College of Medicine at Peoria, Peoria, IL 61656 (United States); Tsung, Andrew J. [Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61656 (United States); Department of Neurosurgery, University of Illinois College of Medicine at Peoria, Peoria, IL 61656 (United States); Illinois Neurological Institute, Peoria, IL 61656 (United States); Velpula, Kiran K., E-mail: velpula@uic.edu [Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61656 (United States); Department of Neurosurgery, University of Illinois College of Medicine at Peoria, Peoria, IL 61656 (United States)

    2016-08-19

    Medulloblastoma (MB) is the most frequent malignant pediatric brain tumor. Current treatment includes surgery, radiation and chemotherapy. However, ongoing treatment in patients is further classified according to the presence or absence of metastasis. Since metastatic medulloblastoma are refractory to current treatments, there is need to identify novel biomarkers that could be used to reduce metastatic potential, and more importantly be targeted therapeutically. Previously, we showed that ionizing radiation-induced uPAR overexpression is associated with increased accumulation of β-catenin in the nucleus. We further demonstrated that uPAR protein act as cytoplasmic sequestration factor for a novel basic helix-loop-helix transcription factor, Hand1. Among the histological subtypes classical and desmoplastic subtypes account for the majority while large cell/anaplastic variant is most commonly associated with metastatic disease. In this present study using immunohistochemical approach and patient data mining for the first time, we demonstrated that Hand1 expression is observed to be downregulated in all the subtypes of medulloblastoma. Previously we showed that Hand1 overexpression regulated medulloblastoma angiogenesis and here we investigated the role of Hand1 in the context of Epithelial-Mesenchymal Transition (EMT). Moreover, UW228 and D283 cells overexpressing Hand1 demonstrated decreased-expression of mesenchymal markers (N-cadherin, β-catenin and SOX2); metastatic marker (SMA); and increased expression of epithelial marker (E-cadherin). Strikingly, human pluripotent stem cell antibody array showed that Hand1 overexpression resulted in substantial decrease in pluripotency markers (Nanog, Oct3/4, Otx2, Flk1) suggesting that Hand1 expression may be essential to attenuate the EMT and our findings underscore a novel role for Hand1 in medulloblastoma metastasis. - Highlights: • Hand1 expression is downregulated in Medulloblastoma. • Hand1 over expression reduce

  1. Hand1 overexpression inhibits medulloblastoma metastasis

    International Nuclear Information System (INIS)

    Asuthkar, Swapna; Guda, Maheedhara R.; Martin, Sarah E.; Antony, Reuben; Fernandez, Karen; Lin, Julian; Tsung, Andrew J.; Velpula, Kiran K.

    2016-01-01

    Medulloblastoma (MB) is the most frequent malignant pediatric brain tumor. Current treatment includes surgery, radiation and chemotherapy. However, ongoing treatment in patients is further classified according to the presence or absence of metastasis. Since metastatic medulloblastoma are refractory to current treatments, there is need to identify novel biomarkers that could be used to reduce metastatic potential, and more importantly be targeted therapeutically. Previously, we showed that ionizing radiation-induced uPAR overexpression is associated with increased accumulation of β-catenin in the nucleus. We further demonstrated that uPAR protein act as cytoplasmic sequestration factor for a novel basic helix-loop-helix transcription factor, Hand1. Among the histological subtypes classical and desmoplastic subtypes account for the majority while large cell/anaplastic variant is most commonly associated with metastatic disease. In this present study using immunohistochemical approach and patient data mining for the first time, we demonstrated that Hand1 expression is observed to be downregulated in all the subtypes of medulloblastoma. Previously we showed that Hand1 overexpression regulated medulloblastoma angiogenesis and here we investigated the role of Hand1 in the context of Epithelial-Mesenchymal Transition (EMT). Moreover, UW228 and D283 cells overexpressing Hand1 demonstrated decreased-expression of mesenchymal markers (N-cadherin, β-catenin and SOX2); metastatic marker (SMA); and increased expression of epithelial marker (E-cadherin). Strikingly, human pluripotent stem cell antibody array showed that Hand1 overexpression resulted in substantial decrease in pluripotency markers (Nanog, Oct3/4, Otx2, Flk1) suggesting that Hand1 expression may be essential to attenuate the EMT and our findings underscore a novel role for Hand1 in medulloblastoma metastasis. - Highlights: • Hand1 expression is downregulated in Medulloblastoma. • Hand1 over expression reduce

  2. American Dream Delayed

    DEFF Research Database (Denmark)

    Khorunzhina, Natalia; Miller, Robert A.

    This paper investigates the delay in homeownership and a subsequent reduction in homeownership rate observed over the past decades. We focus on the delay in giving birth to children and increased labor market participation as contributing factors to homeownership dynamics for prime-age female hou...

  3. Delayed power analysis

    International Nuclear Information System (INIS)

    Adamovich, L.A.; Azarov, V.V.

    1999-01-01

    Time dependent core power behavior in a nuclear reactor is described with well-known neutron kinetics equations. At the same time, two portions are distinguished in energy released from uranium nuclei fission; one released directly at fission and another delayed (residual) portion produced during radioactive decay of fission products. While prompt power is definitely described with kinetics equations, the delayed power presentation still remains outstanding. Since in operation the delayed power part is relatively small (about 6%) operation, it can be neglected for small reactivity disturbances assuming that entire power obeys neutron kinetics equations. In case of a high negative reactivity rapidly inserted in core (e.g. reactor scram initiation) the prompt and delayed components can be calculated separately with practically no impact on each other, employing kinetics equations for prompt power and known approximation formulas for delayed portion, named residual in this specific case. Under substantial disturbances the prompt component in the dynamic process becomes commensurable with delayed portion, thus making necessary to take into account their cross impact. A system of differential equations to describe time-dependent behavior of delayed power is presented. Specific NPP analysis shows a way to significantly simplify the task formulation. (author)

  4. Frequent Nek1 overexpression in human gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Jun [School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai (China); Neurosurgery Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Cai, Yu, E-mail: aihaozuqiu22@163.com [School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai (China); Neurosurgery Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Liu, Pin [Med-X Research Institute, Shanghai Jiao Tong University, Shanghai (China); Zhao, Weiguo [Neurosurgery Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China)

    2016-08-05

    Never in mitosis A (NIMA)-related kinase 1 (Nek1) regulates cell cycle progression to mitosis. Its expression and potential functions in human gliomas have not been studied. Here, our immunohistochemistry (IHC) assay and Western blot assay results showed that Nek1 expression was significantly upregulated in fresh and paraffin-embedded human glioma tissues. Its level in normal brain tissues was low. Nek1 overexpression in human gliomas was correlated with the proliferation marker (Ki-67), tumor grade, Karnofsky performance scale (KPS) and more importantly, patients’ poor survival. Further studies showed that Nek1 expression level was also increased in multiple human glioma cell lines (U251-MG, U87-MG, U118, H4 and U373). Significantly, siRNA-mediated knockdown of Nek1 inhibited glioma cell (U87-MG/U251-MG) growth. Nek1 siRNA also sensitized U87-MG/U251-MG cells to temozolomide (TMZ), causing a profound apoptosis induction and growth inhibition. The current study indicates Nek1 might be a novel and valuable oncotarget of glioma, it is important for glioma cell growth and TMZ-resistance. - Highlights: • Nek1 is upregulated in multiple human glioma tissues and cell lines. • Nek1 overexpression correlates with glioma grades and patients’ KPS score. • Nek1 overexpression correlates with patients’ poor overall survival. • siRNA knockdown of Nek1 inhibits glioma cell growth. • siRNA knockdown of Nek1 sensitizes human glioma cells to temozolomide.

  5. Frequent Nek1 overexpression in human gliomas

    International Nuclear Information System (INIS)

    Zhu, Jun; Cai, Yu; Liu, Pin; Zhao, Weiguo

    2016-01-01

    Never in mitosis A (NIMA)-related kinase 1 (Nek1) regulates cell cycle progression to mitosis. Its expression and potential functions in human gliomas have not been studied. Here, our immunohistochemistry (IHC) assay and Western blot assay results showed that Nek1 expression was significantly upregulated in fresh and paraffin-embedded human glioma tissues. Its level in normal brain tissues was low. Nek1 overexpression in human gliomas was correlated with the proliferation marker (Ki-67), tumor grade, Karnofsky performance scale (KPS) and more importantly, patients’ poor survival. Further studies showed that Nek1 expression level was also increased in multiple human glioma cell lines (U251-MG, U87-MG, U118, H4 and U373). Significantly, siRNA-mediated knockdown of Nek1 inhibited glioma cell (U87-MG/U251-MG) growth. Nek1 siRNA also sensitized U87-MG/U251-MG cells to temozolomide (TMZ), causing a profound apoptosis induction and growth inhibition. The current study indicates Nek1 might be a novel and valuable oncotarget of glioma, it is important for glioma cell growth and TMZ-resistance. - Highlights: • Nek1 is upregulated in multiple human glioma tissues and cell lines. • Nek1 overexpression correlates with glioma grades and patients’ KPS score. • Nek1 overexpression correlates with patients’ poor overall survival. • siRNA knockdown of Nek1 inhibits glioma cell growth. • siRNA knockdown of Nek1 sensitizes human glioma cells to temozolomide.

  6. YUCCA6 over-expression demonstrates auxin function in delaying leaf senescence in Arabidopsis thaliana

    KAUST Repository

    Kim, Jeong Im; Murphy, Angus S.; Baek, Dongwon; Lee, Shin-Woo; Yun, Dae-Jin; Bressan, Ray A.; Narasimhan, Meena L.

    2011-01-01

    The Arabidopsis thaliana YUCCA family of flavin monooxygenase proteins catalyses a rate-limiting step in de novo auxin biosynthesis. A YUCCA6 activation mutant, yuc6-1D, has been shown to contain an elevated free IAA level and to display typical

  7. Neutron delayed choice experiments

    International Nuclear Information System (INIS)

    Bernstein, H.J.

    1986-01-01

    Delayed choice experiments for neutrons can help extend the interpretation of quantum mechanical phenomena. They may also rule out alternative explanations which static interference experiments allow. A simple example of a feasible neutron test is presented and discussed. (orig.)

  8. Quad nanosecond delay module

    International Nuclear Information System (INIS)

    McDonald, R.J.; Hunter, J.B.; Wozniak, G.J.

    1986-04-01

    Four nanosecond (ns) delay units have been designed to fit in a single-width NIM module. This module is particularly suited for use in conjunction with quad constant fraction timing discriminators (CFTDs) since it has four delay units that can be placed adjacent to the four units of the CFTD. A series of different length cables connected via DIP toggle switches provide delays of 0.60 ns in 4 ns increments. Thus, the CFTD delay can be optimized for pulses of different rise times from approx.10-100 ns. Design work for the PC board and silkscreening of the front panel were done with the MacDraw program on the Apple Mackintosh computer and printed with the Lasewriter printer. 6 refs

  9. Delayed rule following

    OpenAIRE

    Schmitt, David R.

    2001-01-01

    Although the elements of a fully stated rule (discriminative stimulus [SD], some behavior, and a consequence) can occur nearly contemporaneously with the statement of the rule, there is often a delay between the rule statement and the SD. The effects of this delay on rule following have not been studied in behavior analysis, but they have been investigated in rule-like settings in the areas of prospective memory (remembering to do something in the future) and goal pursuit. Discriminative even...

  10. Vernier Delay Unit

    International Nuclear Information System (INIS)

    Pierce, W.B.

    1984-10-01

    This module will accept differential ECL pulses from the auxiliary rear panel or NIM level pulses from the front panel. The pulses are produced at the output with a fixed delay that is software programmable in steps of 0.1 ns over the range of 0.1 to 10.5 ns. Multiple outputs are available at the front panel. Minimum delay through the module is 9 ns

  11. Quad precision delay generator

    International Nuclear Information System (INIS)

    Krishnan, Shanti; Gopalakrishnan, K.R.; Marballi, K.R.

    1997-01-01

    A Quad Precision Delay Generator delays a digital edge by a programmed amount of time, varying from nanoseconds to microseconds. The output of this generator has an amplitude of the order of tens of volts and rise time of the order of nanoseconds. This was specifically designed and developed to meet the stringent requirements of the plasma focus experiments. Plasma focus is a laboratory device for producing and studying nuclear fusion reactions in hot deuterium plasma. 3 figs

  12. Modelling delays in pharmacokinetics

    International Nuclear Information System (INIS)

    Farooqi, Z.H.; Lambrecht, R.M.

    1990-01-01

    Linear system analysis has come to form the backbone of pharmacokinetics. Natural systems usually involve time delays, thus models incorporating them would be an order closer approximation to the real world compared to those that do not. Delays may be modelled in several ways. The approach considered in this study is to have a discrete-time delay dependent rate with the delay respresenting the duration between the entry of a drug into a compartment and its release in some form (may be as a metabolite) from the compartment. Such a delay may be because of one or more of several physiological reasons, like, formation of a reservoir, slow metabolism, or receptor binding. The mathematical structure this gives rise to is a system of delay-differential equations. Examples are given of simple one and two compartment systems with drugs like bumetanide, carbamazepine, and quinolone-caffeine interaction. In these examples generally a good fit is obtained and the suggested models form a good approximation. 21 refs., 6 figs

  13. Experimental Nonalcoholic Steatohepatitis and Liver Fibrosis Are Ameliorated by Pharmacologic Activation of Nrf2 (NF-E2 p45-Related Factor 2

    Directory of Open Access Journals (Sweden)

    Ritu S. Sharma

    2018-01-01

    Conclusions: Pharmacologic activation of Nrf2 in mice that had already been rendered obese and insulin resistant reversed insulin resistance, suppressed hepatic steatosis, and mitigated against NASH and liver fibrosis, effects that we principally attribute to inhibition of ER, inflammatory, and oxidative stress.

  14. Overexpressed TP73 induces apoptosis in medulloblastoma

    International Nuclear Information System (INIS)

    Castellino, Robert C; De Bortoli, Massimiliano; Lin, Linda L; Skapura, Darlene G; Rajan, Jessen A; Adesina, Adekunle M; Perlaky, Laszlo; Irwin, Meredith S; Kim, John YH

    2007-01-01

    Medulloblastoma is the most common malignant brain tumor of childhood. Children who relapse usually die of their disease, which reflects resistance to radiation and/or chemotherapy. Improvements in outcome require a better understanding of the molecular basis of medulloblastoma growth and treatment response. TP73 is a member of the TP53 tumor suppressor gene family that has been found to be overexpressed in a variety of tumors and mediates apoptotic responses to genotoxic stress. In this study, we assessed expression of TP73 RNA species in patient tumor specimens and in medulloblastoma cell lines, and manipulated expression of full-length TAp73 and amino-terminal truncated ΔNp73 to assess their effects on growth. We analyzed medulloblastoma samples from thirty-four pediatric patients and the established medulloblastoma cell lines, Daoy and D283MED, for expression of TP73 RNA including the full-length transcript and the 5'-terminal variants that encode the ΔNp73 isoform, as well as TP53 RNA using quantitative real time-RTPCR. Protein expression of TAp73 and ΔNp73 was quantitated with immunoblotting methods. Clinical outcome was analyzed based on TP73 RNA and p53 protein expression. To determine effects of overexpression or knock-down of TAp73 and ΔNp73 on cell cycle and apoptosis, we analyzed transiently transfected medulloblastoma cell lines with flow cytometric and TUNEL methods. Patient medulloblastoma samples and cell lines expressed full-length and 5'-terminal variant TP73 RNA species in 100-fold excess compared to non-neoplastic brain controls. Western immunoblot analysis confirmed their elevated levels of TAp73 and amino-terminal truncated ΔNp73 proteins. Kaplan-Meier analysis revealed trends toward favorable overall and progression-free survival of patients whose tumors display TAp73 RNA overexpression. Overexpression of TAp73 or ΔNp73 induced apoptosis under basal growth conditions in vitro and sensitized them to cell death in response to

  15. Overexpressed TP73 induces apoptosis in medulloblastoma

    Directory of Open Access Journals (Sweden)

    Perlaky Laszlo

    2007-07-01

    Full Text Available Abstract Background Medulloblastoma is the most common malignant brain tumor of childhood. Children who relapse usually die of their disease, which reflects resistance to radiation and/or chemotherapy. Improvements in outcome require a better understanding of the molecular basis of medulloblastoma growth and treatment response. TP73 is a member of the TP53 tumor suppressor gene family that has been found to be overexpressed in a variety of tumors and mediates apoptotic responses to genotoxic stress. In this study, we assessed expression of TP73 RNA species in patient tumor specimens and in medulloblastoma cell lines, and manipulated expression of full-length TAp73 and amino-terminal truncated ΔNp73 to assess their effects on growth. Methods We analyzed medulloblastoma samples from thirty-four pediatric patients and the established medulloblastoma cell lines, Daoy and D283MED, for expression of TP73 RNA including the full-length transcript and the 5'-terminal variants that encode the ΔNp73 isoform, as well as TP53 RNA using quantitative real time-RTPCR. Protein expression of TAp73 and ΔNp73 was quantitated with immunoblotting methods. Clinical outcome was analyzed based on TP73 RNA and p53 protein expression. To determine effects of overexpression or knock-down of TAp73 and ΔNp73 on cell cycle and apoptosis, we analyzed transiently transfected medulloblastoma cell lines with flow cytometric and TUNEL methods. Results Patient medulloblastoma samples and cell lines expressed full-length and 5'-terminal variant TP73 RNA species in 100-fold excess compared to non-neoplastic brain controls. Western immunoblot analysis confirmed their elevated levels of TAp73 and amino-terminal truncated ΔNp73 proteins. Kaplan-Meier analysis revealed trends toward favorable overall and progression-free survival of patients whose tumors display TAp73 RNA overexpression. Overexpression of TAp73 or ΔNp73 induced apoptosis under basal growth conditions in vitro and

  16. Effect of Bcl-xL overexpression on sialylation of Fc-fusion protein in recombinant Chinese hamster ovary cell cultures.

    Science.gov (United States)

    Lee, Jong Hyun; Kim, Yeon-Gu; Lee, Gyun Min

    2015-01-01

    The sialic acid of glycoproteins secreted by recombinant Chinese hamster ovary (rCHO) cells can be impaired by sialidase under culture conditions which promote the extracellular accumulation of this enzyme. To investigate the effect of Bcl-xL overexpression on the sialylation of glycoproteins produced in rCHO cell culture, two rCHO cell lines producing the same Fc-fusion protein, which were derived from DUKX-B11 and DG44, respectively, were engineered to have regulated Bcl-xL overexpression using the Tet-off system. For both cell lines, Bcl-xL overexpression improved cell viability and extended culture longevity in batch cultures. As a result, a maximum Fc-fusion protein titer increased by Bcl-xL overexpression though the extent of titer enhancement differed between the two cell lines. With Bcl-xL overexpression, the sialylation of Fc-fusion protein, which was assessed by isoelectric focusing gel and sialic acid content analyses, decreased more slowly toward the end of batch cultures. This was because Bcl-xL overexpression delayed the extracellular accumulation of sialidase activity by reducing cell lysis during batch cultures. Taken together, Bcl-xL overexpression in rCHO cell culture increased Fc-fusion protein production and also reduced the impairment of sialylation of Fc-fusion protein by maintaining high viability during batch cultures. © 2015 American Institute of Chemical Engineers.

  17. Optimal Joint Expected Delay Forwarding in Delay Tolerant Networks

    OpenAIRE

    Jia Xu; Xin Feng; Wen Jun Yang; Ru Chuan Wang; Bing Qing Han

    2013-01-01

    Multicopy forwarding schemes have been employed in delay tolerant network (DTN) to improve the delivery delay and delivery rate. Much effort has been focused on reducing the routing cost while retaining high performance. This paper aims to provide an optimal joint expected delay forwarding (OJEDF) protocol which minimizes the expected delay while satisfying a certain constant on the number of forwardings per message. We propose a comprehensive forwarding metric called joint expected delay (JE...

  18. Interleukin-6 overexpression induces pulmonary hypertension.

    Science.gov (United States)

    Steiner, M Kathryn; Syrkina, Olga L; Kolliputi, Narasaish; Mark, Eugene J; Hales, Charles A; Waxman, Aaron B

    2009-01-30

    Inflammatory cytokine interleukin (IL)-6 is elevated in the serum and lungs of patients with pulmonary artery hypertension (PAH). Several animal models of PAH cite the potential role of inflammatory mediators. We investigated role of IL-6 in the pathogenesis of pulmonary vascular disease. Indices of pulmonary vascular remodeling were measured in lung-specific IL-6-overexpressing transgenic mice (Tg(+)) and compared to wild-type (Tg(-)) controls in both normoxic and chronic hypoxic conditions. The Tg(+) mice exhibited elevated right ventricular systolic pressures and right ventricular hypertrophy with corresponding pulmonary vasculopathic changes, all of which were exacerbated by chronic hypoxia. IL-6 overexpression increased muscularization of the proximal arterial tree, and hypoxia enhanced this effect. It also reproduced the muscularization and proliferative arteriopathy seen in the distal arteriolar vessels of PAH patients. The latter was characterized by the formation of occlusive neointimal angioproliferative lesions that worsened with hypoxia and were composed of endothelial cells and T-lymphocytes. IL-6-induced arteriopathic changes were accompanied by activation of proangiogenic factor, vascular endothelial growth factor, the proproliferative kinase extracellular signal-regulated kinase, proproliferative transcription factors c-MYC and MAX, and the antiapoptotic proteins survivin and Bcl-2 and downregulation of the growth inhibitor transforming growth factor-beta and proapoptotic kinases JNK and p38. These findings suggest that IL-6 promotes the development and progression of pulmonary vascular remodeling and PAH through proproliferative antiapoptotic mechanisms.

  19. Overexpression of IGF-I receptor in HeLa cells enhances in vivo radioresponse

    International Nuclear Information System (INIS)

    Kaneko, Haruna; Yu, Dong; Miura, Masahiko

    2007-01-01

    Insulin-like growth factor I receptor (IGF-IR) is a transmembrane receptor tyrosine kinase whose activation strongly promotes cell growth and survival. We previously reported that IGF-IR activity confers intrinsic radioresistance in mouse embryo fibroblasts in vitro. However, it is still unclear whether tumor cells overexpressing IGF-IR exhibit radioresistance in vivo. For this purpose, we established HeLa cells that overexpress IGF-IR (HeLa-R), subcutaneously transplanted these cells into nude mice, and examined radioresponse in the resulting solid tumors. HeLa-R cells exhibited typical in vitro phenotypes generally observed in IGF-IR-overexpressing cells, as well as significant intrinsic radioresistance in vitro compared with parent cells. As expected, the transplanted HeLa-R tumors grew at a remarkably higher rate than parent tumors. Histological analysis revealed that HeLa-R tumors expressed more VEGF and had a higher density of tumor vessels. Unexpectedly, a marked growth delay was observed in HeLa-R tumors following 10 Gy of X-irradiation. Immunostaining of HeLa-R tumors for the hypoxia marker pimonidazole revealed a significantly lower level of hypoxic cells. Moreover, clamp hypoxia significantly increased radioresistance in HeLa-R tumors. Tumor microenvironments in vivo generated by the IGF-IR expression thus could be a major factor in determining the tumor radioresponse in vivo

  20. Targeted overexpression of EZH2 in the mammary gland disrupts ductal morphogenesis and causes epithelial hyperplasia.

    Science.gov (United States)

    Li, Xin; Gonzalez, Maria E; Toy, Katherine; Filzen, Tracey; Merajver, Sofia D; Kleer, Celina G

    2009-09-01

    The Polycomb group protein enhancer of zeste homolog 2 (EZH2), which has roles during development of numerous tissues, is a critical regulator of cell type identity. Overexpression of EZH2 has been detected in invasive breast carcinoma tissue samples and is observed in human breast tissue samples of morphologically normal lobules up to 12 years before the development of breast cancer. The function of EZH2 during preneoplastic progression in the mammary gland is unknown. To investigate the role of EZH2 in the mammary gland, we targeted the expression of EZH2 to mammary epithelial cells using the mouse mammary tumor virus long terminal repeat. EZH2 overexpression resulted in aberrant terminal end bud architecture. By the age of 4 months, 100% of female mouse mammary tumor virus-EZH2 virgin mice developed intraductal epithelial hyperplasia resembling the human counterpart accompanied by premature differentiation of ductal epithelial cells and up-regulation of the luminal marker GATA-3. In addition, remodeling of the mammary gland after parturition was impaired and EZH2 overexpression caused delayed involution. Mechanistically, we found that EZH2 physically interacts with beta-catenin, inducing beta-catenin nuclear accumulation in mammary epithelial cells and activating Wnt/beta-catenin signaling. The biological significance of these data to human hyperplasias is demonstrated by EZH2 up-regulation and colocalization with beta-catenin in human intraductal epithelial hyperplasia, the earliest histologically identifiable precursor of breast carcinoma.

  1. Assessing delay discounting in mice

    OpenAIRE

    Mitchell, Suzanne H.

    2014-01-01

    Delay discounting (also intertemporal choice or impulsive choice) is the process by which delayed outcomes, such as delayed food delivery, are valued less than the same outcomes delivered immediately or with a shorter delay. This process is of interest because many psychopathologies, including substance dependence, pathological gambling, attention deficit hyperactivity disorder and conduct disorder, are characterized by heightened levels of delay discounting. Some of these disorders are herit...

  2. Estimating Delays In ASIC's

    Science.gov (United States)

    Burke, Gary; Nesheiwat, Jeffrey; Su, Ling

    1994-01-01

    Verification is important aspect of process of designing application-specific integrated circuit (ASIC). Design must not only be functionally accurate, but must also maintain correct timing. IFA, Intelligent Front Annotation program, assists in verifying timing of ASIC early in design process. This program speeds design-and-verification cycle by estimating delays before layouts completed. Written in C language.

  3. Permissible Delay in Payments

    Directory of Open Access Journals (Sweden)

    Yung-Fu Huang

    2007-01-01

    Full Text Available The main purpose of this paper wants to investigate the optimal retailer's lot-sizing policy with two warehouses under partially permissible delay in payments within the economic order quantity (EOQ framework. In this paper, we want to extend that fully permissible delay in payments to the supplier would offer the retailer partially permissible delay in payments. That is, the retailer must make a partial payment to the supplier when the order is received. Then the retailer must pay off the remaining balance at the end of the permissible delay period. In addition, we want to add the assumption that the retailer's storage space is limited. That is, the retailer will rent the warehouse to store these exceeding items when the order quantity is larger than retailer's storage space. Under these conditions, we model the retailer's inventory system as a cost minimization problem to determine the retailer's optimal cycle time and optimal order quantity. Three theorems are developed to efficiently determine the optimal replenishment policy for the retailer. Finally, numerical examples are given to illustrate these theorems and obtained a lot of managerial insights.

  4. Delayed neutrons in ANSTO

    International Nuclear Information System (INIS)

    Wall, T.

    1988-01-01

    Delayed neutron analysis carried out at the Australian Nuclear Scientific and Technology Organization facilities, provides a fast, high sensitivity, low cost, reliable method, particularly suitable for large batches of samples, and for non destructive analysis of a range of materials. While its main use has been in uranium exploration, other applications include archeological investigations, agriculture, oceanography and biology

  5. Overexpression of antioxidant enzymes in diaphragm muscle does not alter contraction-induced fatigue or recovery

    Science.gov (United States)

    McClung, Joseph M.; DeRuisseau, Keith C.; Whidden, Melissa A.; Van Remmen, Holly; Richardson, Arlan; Song, Wook; Vrabas, Ioannis S.; Powers, Scott K.

    2010-01-01

    Low levels of reactive oxygen species (ROS) production are necessary to optimize muscle force production in unfatigued muscle. In contrast, sustained high levels of ROS production have been linked to impaired muscle force production and contraction-induced skeletal muscle fatigue. Using genetically engineered mice, we tested the hypothesis that the independent transgenic overexpression of catalase (CAT), copper/zinc superoxide dismutase (CuZnSOD; SOD1) or manganese superoxide dismutase (MnSOD; SOD2) antioxidant enzymes would negatively affect force production in unfatigued diaphragm muscle but would delay the development of muscle fatigue and enhance force recovery after fatiguing contractions. Diaphragm muscle from wild-type littermates (WT) and from CAT, SOD1 and SOD2 overexpressing mice were subjected to an in vitro contractile protocol to investigate the force–frequency characteristics, the fatigue properties and the time course of recovery from fatigue. The CAT, SOD1 and SOD2 overexpressors produced less specific force (in N cm−2) at stimulation frequencies of 20–300 Hz and produced lower maximal tetanic force than WT littermates. The relative development of muscle fatigue and recovery from fatigue were not influenced by transgenic overexpression of any antioxidant enzyme. Morphologically, the mean cross-sectional area (in μm2) of diaphragm myofibres expressing myosin heavy chain type IIA was decreased in both CAT and SOD2 transgenic animals, and the percentage of non-contractile tissue increased in diaphragms from all transgenic mice. In conclusion, our results do not support the hypothesis that overexpression of independent antioxidant enzymes protects diaphragm muscle from contraction-induced fatigue or improves recovery from fatigue. Moreover, our data are consistent with the concept that a basal level of ROS is important to optimize muscle force production, since transgenic overexpression of major cellular antioxidants is associated with

  6. Growth Hormone Overexpression Disrupts Reproductive Status Through Actions on Leptin

    Directory of Open Access Journals (Sweden)

    Ji Chen

    2018-03-01

    pituitary might be part of the response to overexpression of GH and the resulting delay in puberty onset.

  7. Topological Acoustic Delay Line

    Science.gov (United States)

    Zhang, Zhiwang; Tian, Ye; Cheng, Ying; Wei, Qi; Liu, Xiaojun; Christensen, Johan

    2018-03-01

    Topological protected wave engineering in artificially structured media is at the frontier of ongoing metamaterials research that is inspired by quantum mechanics. Acoustic analogues of electronic topological insulators have recently led to a wealth of new opportunities in manipulating sound propagation with strikingly unconventional acoustic edge modes immune to backscattering. Earlier fabrications of topological insulators are characterized by an unreconfigurable geometry and a very narrow frequency response, which severely hinders the exploration and design of useful devices. Here we establish topologically protected sound in reconfigurable phononic crystals that can be switched on and off simply by rotating its three-legged "atoms" without altering the lattice structure. In particular, we engineer robust phase delay defects that take advantage of the ultrabroadband reflection-free sound propagation. Such topological delay lines serve as a paradigm in compact acoustic devices, interconnects, and electroacoustic integrated circuits.

  8. Delayed traumatic intracranial hematoma

    International Nuclear Information System (INIS)

    Tomita, Hiroki

    1984-01-01

    CT was performed serially within 24 hours after head injury in 64 patients having Glasgow Coma Scale of 14 or less or cranial fracture shown on roentgenogram. Delayed traumatic extradural hematoma was observed within 7-12 hours after head injury in 6 cases (9.4%). This was prominent in the frontal and occipital regions (67%). Good recovery was seen in 83.3%. Delayed traumatic intracerebral hematoma was observed within 6-24 hours after head injury in 17 cases (26.6%). This higher incidence was related to contre coup injury. Conservative treatment was possible in 14 of the 17 patients (82.4%), showing good recovery in 70%. (Namekawa, K.)

  9. Overexpression of AtGRDP2, a novel glycine-rich domain protein, accelerates plant growth and improves stress tolerance

    Directory of Open Access Journals (Sweden)

    Maria Azucena Ortega-Amaro

    2015-01-01

    Full Text Available Proteins with glycine-rich signatures have been reported in a wide variety of organisms including plants, mammalians, fungi, and bacteria. Plant glycine-rich protein genes exhibit developmental and tissue-specific expression patterns. Herein, we present the characterization of the AtGRDP2 gene using Arabidopsis null and knockdown mutants and, Arabidopsis and lettuce over-expression lines. AtGRDP2 encodes a short glycine-rich domain protein, containing a DUF1399 domain and a putative RNA recognition motif. AtGRDP2 transcript is mainly expressed in Arabidopsis floral organs, and its deregulation in Arabidopsis Atgrdp2 mutants and 35S::AtGRDP2 over-expression lines produces alterations in development. The 35S::AtGRDP2 over-expression lines grow faster than the WT, while the Atgrdp2 mutants have a delay in growth and development. The over-expression lines accumulate higher levels of indole-3-acetic acid and, have alterations in the expression pattern of ARF6, ARF8 and miR167 regulators of floral development and auxin signaling. Under salt stress conditions, 35S::AtGRDP2 over-expression lines displayed higher tolerance and increased expression of stress marker genes. Likewise, transgenic lettuce plants over-expressing the AtGRDP2 gene manifest increased growth rate and early flowering time. Our data reveal an important role for AtGRDP2 in Arabidopsis development and stress response, and suggest a connection between AtGRDP2 and auxin signaling.

  10. Time-Delay Interferometry

    Directory of Open Access Journals (Sweden)

    Massimo Tinto

    2014-08-01

    Full Text Available Equal-arm detectors of gravitational radiation allow phase measurements many orders of magnitude below the intrinsic phase stability of the laser injecting light into their arms. This is because the noise in the laser light is common to both arms, experiencing exactly the same delay, and thus cancels when it is differenced at the photo detector. In this situation, much lower level secondary noises then set the overall performance. If, however, the two arms have different lengths (as will necessarily be the case with space-borne interferometers, the laser noise experiences different delays in the two arms and will hence not directly cancel at the detector. In order to solve this problem, a technique involving heterodyne interferometry with unequal arm lengths and independent phase-difference readouts has been proposed. It relies on properly time-shifting and linearly combining independent Doppler measurements, and for this reason it has been called time-delay interferometry (TDI. This article provides an overview of the theory, mathematical foundations, and experimental aspects associated with the implementation of TDI. Although emphasis on the application of TDI to the Laser Interferometer Space Antenna (LISA mission appears throughout this article, TDI can be incorporated into the design of any future space-based mission aiming to search for gravitational waves via interferometric measurements. We have purposely left out all theoretical aspects that data analysts will need to account for when analyzing the TDI data combinations.

  11. Overexpression of osteoprotegerin promotes preosteoblast differentiation to mature osteoblasts

    NARCIS (Netherlands)

    Yu, Hongyou; de Vos, Paul; Ren, Yijin

    OBJECTIVE: The hypothesis of the present study is that overexpression of osteoprotegerin (OPG) promotes preosteoblast maturation. MATERIALS AND METHODS: The preosteoblast cell line MC3T3-E1 was transfected with OPG overexpression. OPG expression was confirmed by enzyme-linked immunosorbent assay

  12. Dimethylarginine Dimethylaminohydrolase Overexpression enhances Insulin Sensitivity

    Science.gov (United States)

    Sydow, Karsten; Mondon, Carl E.; Schrader, Joerg; Konishi, Hakuoh; Cooke, John P.

    2011-01-01

    Objective Previous studies suggest that nitric oxide (NO) may modulate insulin-induced uptake of glucose in insulin-sensitive tissues. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase (NOS). We hypothesized that a reduction in endogenous ADMA would increase NO synthesis and thereby enhance insulin sensitivity. Methods and Results To test this hypothesis we employed a transgenic mouse in which we overexpressed human dimethylarginine dimethylaminohydrolase (DDAH-I). The DDAH-I mice had lower plasma ADMA at all ages (22–70 weeks) by comparison to wild-type (WT) littermates. With a glucose challenge, WT mice showed a prompt increase in ADMA, whereas DDAH-I mice had a blunted response. Furthermore, DDAH-I mice had a blunted increase in plasma insulin and glucose levels after glucose challenge, with a 50% reduction in the insulin resistence index, consistent with enhanced sensitivity to insulin. In liver, we observed an increased Akt phosphorylation in the DDAH-I mice after i.p. glucose challenge. Incubation of skeletal muscle from WT mice ex vivo with ADMA (2μM) markedly suppressed insulin-induced glycogen synthesis in fast-twitch but not slow-twitch muscle. Conclusions These findings suggest that the endogenous NOS inhibitor ADMA reduces insulin sensitivity, consistent with previous observations that NO plays a role in insulin sensitivity. PMID:18239148

  13. Delayed child-bearing.

    Science.gov (United States)

    Johnson, Jo-Ann; Tough, Suzanne

    2012-01-01

    To provide an overview of delayed child-bearing and to describe the implications for women and health care providers. Delayed child-bearing, which has increased greatly in recent decades, is associated with an increased risk of infertility, pregnancy complications, and adverse pregnancy outcome. This guideline provides information that will optimize the counselling and care of Canadian women with respect to their reproductive choices. Maternal age is the most important determinant of fertility, and obstetric and perinatal risks increase with maternal age. Many women are unaware of the success rates or limitations of assisted reproductive technology and of the increased medical risks of delayed child-bearing, including multiple births, preterm delivery, stillbirth, and Caesarean section. This guideline provides a framework to address these issues. Studies published between 2000 and August 2010 were retrieved through searches of PubMed and the Cochrane Library using appropriate key words (delayed child-bearing, deferred pregnancy, maternal age, assisted reproductive technology, infertility, and multiple births) and MeSH terms (maternal age, reproductive behaviour, fertility). The Internet was also searched using similar key words, and national and international medical specialty societies were searched for clinical practice guidelines and position statements. Data were extracted based on the aims, sample, authors, year, and results. The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). The Society of Obstetricians and Gynaecologists of Canada. RECOMMENDATIONS 1. Women who delay child-bearing are at increased risk of infertility. Prospective parents, especially women, should know that their fecundity and fertility begin to decline significantly after 32 years of age. Prospective parents should know that assisted reproductive technologies cannot guarantee a live birth or completely

  14. Delaying information search

    Directory of Open Access Journals (Sweden)

    Yaniv Shani

    2012-11-01

    Full Text Available In three studies, we examined factors that may temporarily attenuate information search. People are generally curious and dislike uncertainty, which typically encourages them to look for relevant information. Despite these strong forces that promote information search, people sometimes deliberately delay obtaining valuable information. We find they may do so when they are concerned that the information might interfere with future pleasurable activities. Interestingly, the decision to search or to postpone searching for information is influenced not only by the value and importance of the information itself but also by well-being maintenance goals related to possible detrimental effects that negative knowledge may have on unrelated future plans.

  15. Vehicle barrier with access delay

    Science.gov (United States)

    Swahlan, David J; Wilke, Jason

    2013-09-03

    An access delay vehicle barrier for stopping unauthorized entry into secure areas by a vehicle ramming attack includes access delay features for preventing and/or delaying an adversary from defeating or compromising the barrier. A horizontally deployed barrier member can include an exterior steel casing, an interior steel reinforcing member and access delay members disposed within the casing and between the casing and the interior reinforcing member. Access delay members can include wooden structural lumber, concrete and/or polymeric members that in combination with the exterior casing and interior reinforcing member act cooperatively to impair an adversarial attach by thermal, mechanical and/or explosive tools.

  16. Delayed rule following.

    Science.gov (United States)

    Schmitt, D R

    2001-01-01

    Although the elements of a fully stated rule (discriminative stimulus [S(D)], some behavior, and a consequence) can occur nearly contemporaneously with the statement of the rule, there is often a delay between the rule statement and the S(D). The effects of this delay on rule following have not been studied in behavior analysis, but they have been investigated in rule-like settings in the areas of prospective memory (remembering to do something in the future) and goal pursuit. Discriminative events for some behavior can be event based (a specific setting stimulus) or time based. The latter are more demanding with respect to intention following and show age-related deficits. Studies suggest that the specificity with which the components of a rule (termed intention) are stated has a substantial effect on intention following, with more detailed specifications increasing following. Reminders of an intention, too, are most effective when they refer specifically to both the behavior and its occasion. Covert review and written notes are two effective strategies for remembering everyday intentions, but people who use notes appear not to be able to switch quickly to covert review. By focusing on aspects of the setting and rule structure, research on prospective memory and goal pursuit expands the agenda for a more complete explanation of rule effects.

  17. Pseudotumoral delayed cerebral radionecrosis

    International Nuclear Information System (INIS)

    Ciaudo-Lacroix, C.; Lapresle, J.

    1985-01-01

    A 60 year-old woman with a scalp epithelioma underwent radiotherapy, the dose being 57 Gray. A first epileptic seizure occurred twenty months later. Neurological examination revealed signs of left hemisphere involvement. γEG, angiography, CT scans, demonstrated a pseudotumoral avascular process. On account of the localisation, the patient being right-handed, no surgical procedure was performed. In spite of corticotherapy and anticonvulsive treatment, seizures recurred and neurological signs slowly progressed. The patient died, 22 months after the first seizure, of an associated disseminated carcinoma with cachexia. Neuropathological examination showed a massive lesion presenting all the features of delayed radionecrosis in the left hemisphere: situated mainly in the white matter; numerous vascular abnormalities; wide-spread demyelination; disappearance of oligoglial cells. The Authors recall the clinical and anatomical aspects of this condition for which the only successful treatment is surgical removal when location and size of the lesion permit. Finally, the mechanisms which have been proposed to explain this delayed cerebral radionecrosis are discussed [fr

  18. Pseudotumoral delayed cerebral radionecrosis

    Energy Technology Data Exchange (ETDEWEB)

    Ciaudo-Lacroix, C; Lapresle, J [Centre Hospitalier de Bicetre, 94 - Le Kremlin-Bicetre (France)

    1985-01-01

    A 60 year-old woman with a scalp epithelioma underwent radiotherapy, the dose being 57 Gray. A first epileptic seizure occurred twenty months later. Neurological examination revealed signs of left hemisphere involvement. ..gamma..EG, angiography, CT scans, demonstrated a pseudotumoral avascular process. On account of the localisation, the patient being right-handed, no surgical procedure was performed. In spite of corticotherapy and anticonvulsive treatment, seizures recurred and neurological signs slowly progressed. The patient died, 22 months after the first seizure, of an associated disseminated carcinoma with cachexia. Neuropathological examination showed a massive lesion presenting all the features of delayed radionecrosis in the left hemisphere: situated mainly in the white matter; numerous vascular abnormalities; wide-spread demyelination; disappearance of oligoglial cells. The Authors recall the clinical and anatomical aspects of this condition for which the only successful treatment is surgical removal when location and size of the lesion permit. Finally, the mechanisms which have been proposed to explain this delayed cerebral radionecrosis are discussed.

  19. C-MET overexpression and amplification in gliomas.

    Science.gov (United States)

    Kwak, Yoonjin; Kim, Seong-Ik; Park, Chul-Kee; Paek, Sun Ha; Lee, Soon-Tae; Park, Sung-Hye

    2015-01-01

    We investigated c-Met overexpression and MET gene amplification in gliomas to determine their incidence and prognostic significance. c-Met immunohistochemistry and MET gene fluorescence in situ hybridization were carried out on tissue microarrays from 250 patients with gliomas (137 grade IV GBMs and 113 grade II and III diffuse gliomas). Clinicopathological features of these cases were reviewed. c-Met overexpression and MET gene amplification were detected in 13.1% and 5.1% of the GBMs, respectively. All the MET-amplified cases showed c-Met overexpression, but MET amplification was not always concordant with c-Met overexpression. None of grade II and III gliomas demonstrated c-Met overexpression or MET gene amplification. Mean survival of the GBM patients with MET amplification was not significantly different from patients without MET amplification (P=0.155). However, GBM patients with c-Met overexpression survived longer than patients without c-Met overexpression (P=0.035). Although MET amplification was not related to poor GBM prognosis, it is partially associated with the aggressiveness of gliomas, as MET amplification was found only in grade IV, not in grade II and III gliomas. We suggest that MET inhibitor therapy may be beneficial in about 5% GBMs, which was the incidence of MET gene amplification found in the patients included in this study.

  20. Neuroglobin Overexpression Inhibits AMPK Signaling and Promotes Cell Anabolism.

    Science.gov (United States)

    Cai, Bin; Li, Wenjun; Mao, XiaoOu; Winters, Ali; Ryou, Myoung-Gwi; Liu, Ran; Greenberg, David A; Wang, Ning; Jin, Kunlin; Yang, Shao-Hua

    2016-03-01

    Neuroglobin (Ngb) is a recently discovered globin with preferential localization to neurons. Growing evidence indicates that Ngb has distinct physiological functions separate from the oxygen storage and transport roles of other globins, such as hemoglobin and myoglobin. We found increased ATP production and decreased glycolysis in Ngb-overexpressing immortalized murine hippocampal cell line (HT-22), in parallel with inhibition of AMP-activated protein kinase (AMPK) signaling and activation of acetyl-CoA carboxylase (ACC). In addition, lipid and glycogen content was increased in Ngb-overexpressing HT-22 cells. AMPK signaling was also inhibited in the brain and heart from Ngb-overexpressing transgenic mice. Although Ngb overexpression did not change glycogen content in whole brain, glycogen synthase was activated in cortical neurons of Ngb-overexpressing mouse brain and Ngb overexpression primary neurons. Moreover, lipid and glycogen content was increased in hearts derived from Ngb-overexpressing mice. These findings suggest that Ngb functions as a metabolic regulator and enhances cellular anabolism through the inhibition of AMPK signaling.

  1. Cloning, overexpression, and characterization of cobrotoxin

    International Nuclear Information System (INIS)

    Hsieh, H.-C.; Kumar, Thallampuranam Krishnaswamy S.; Yu Chin

    2004-01-01

    Cobrotoxin (CBTX) is a highly toxic short neurotoxin, isolated from the Taiwan cobra (Naja naja atra) venom. In the present study for the first time we report the cloning and expression of CBTX in high yields (12 mg/L) in Escherichia coli. CBTX fused to the IgG-binding domain of protein A (IgG-CBTX) was expressed in the soluble form. The misfolded CBTX portion (of the overexpressed fusion protein) was refolded under optimal redox conditions. The fusion protein (IgG-CBTX) was observed to undergo autocatalytic cleavage to yield CBTX with additional 5 amino acids upstream of its N-terminal end. The far UV and near UV circular dichroism spectra of the recombinant CBTX were identical to those of the toxin isolated from the crude venom source. Recombinant CBTX was isotope labeled ( 15 N and 13 C) and all the resonances ( 1 H, 13 C, and 15 N) in the protein have been unambiguously assigned. 1 H- 15 N HSQC spectrum of recombinant CBTX revealed that the protein is in a biologically active conformation. 1 H- 15 N chemical shift perturbation data showed that recombinant CBTX binds to a peptide derived from the α7 subunit of the Torpedo acetylcholine receptor (AchR) with high affinity. The AchR peptide is found to bind to residues located at the tip of Loop-2 in CBTX. The results of the present study provide an avenue to understand the structural basis for the high toxicity exhibited by CBTX. In addition, complete resonance assignments in CBTX (reported in this study) are expected to trigger intensive research towards the design of new pharmacological agents against certain neural disorders

  2. Stability and delay sensitivity of neutral fractional-delay systems.

    Science.gov (United States)

    Xu, Qi; Shi, Min; Wang, Zaihua

    2016-08-01

    This paper generalizes the stability test method via integral estimation for integer-order neutral time-delay systems to neutral fractional-delay systems. The key step in stability test is the calculation of the number of unstable characteristic roots that is described by a definite integral over an interval from zero to a sufficient large upper limit. Algorithms for correctly estimating the upper limits of the integral are given in two concise ways, parameter dependent or independent. A special feature of the proposed method is that it judges the stability of fractional-delay systems simply by using rough integral estimation. Meanwhile, the paper shows that for some neutral fractional-delay systems, the stability is extremely sensitive to the change of time delays. Examples are given for demonstrating the proposed method as well as the delay sensitivity.

  3. Delayed breast implant reconstruction

    DEFF Research Database (Denmark)

    Hvilsom, Gitte B.; Hölmich, Lisbet R.; Steding-Jessen, Marianne

    2012-01-01

    We evaluated the association between radiation therapy and severe capsular contracture or reoperation after 717 delayed breast implant reconstruction procedures (288 1- and 429 2-stage procedures) identified in the prospective database of the Danish Registry for Plastic Surgery of the Breast during...... of radiation therapy was associated with a non-significantly increased risk of reoperation after both 1-stage (HR = 1.4; 95% CI: 0.7-2.5) and 2-stage (HR = 1.6; 95% CI: 0.9-3.1) procedures. Reconstruction failure was highest (13.2%) in the 2-stage procedures with a history of radiation therapy. Breast...... reconstruction approaches other than implants should be seriously considered among women who have received radiation therapy....

  4. Delay tolerant networks

    CERN Document Server

    Gao, Longxiang; Luan, Tom H

    2015-01-01

    This brief presents emerging and promising communication methods for network reliability via delay tolerant networks (DTNs). Different from traditional networks, DTNs possess unique features, such as long latency and unstable network topology. As a result, DTNs can be widely applied to critical applications, such as space communications, disaster rescue, and battlefield communications. The brief provides a complete investigation of DTNs and their current applications, from an overview to the latest development in the area. The core issue of data forward in DTNs is tackled, including the importance of social characteristics, which is an essential feature if the mobile devices are used for human communication. Security and privacy issues in DTNs are discussed, and future work is also discussed.

  5. [Overexpression of FKS1 to improve yeast autolysis-stress].

    Science.gov (United States)

    Li, Jia; Wang, Jinjing; Li, Qi

    2015-09-01

    With the development of high gravity brewing, yeast cells are exposed to multiple brewing-associated stresses, such as increased osmotic pressure, enhanced alcohol concentration and nutritional imbalance. These will speed up yeast autolysis, which seriously influence beer flavor and quality. To increase yeast anti-autolytic ability, FKS1 overexpression strain was constructed by 18S rDNA. The concentration of β-1,3-glucan of overexpression strain was 62% higher than that of wild type strain. Meantime, FKS1 overexpression strain increased anti-stress ability at 8% ethanol, 0.4 mol/L NaCl and starvation stress. Under simulated autolysis, FKS1 showed good anti-autolytic ability by slower autolysis. These results confirms the potential of FKS1 overexpression to tackle yeast autolysis in high-gravity brewing.

  6. Transgenic overexpression of BAFF regulates the expression of ...

    Indian Academy of Sciences (India)

    To investigate whether transgenic overexpression of the zebrafish BAFF leads to ... and BAFF proteins were expressed separately and confirmed in HeLa cells. ... body homogenate of zebrafish and demonstrated a significant increase in ...

  7. APP/SOD1 overexpressing mice present reduced neuropathic pain sensitivity.

    Science.gov (United States)

    Kotulska, Katarzyna; Larysz-Brysz, Magdalena; LePecheur, Marie; Marcol, Wiesław; Olakowska, Edyta; Lewin-Kowalik, Joanna; London, Jacqueline

    2011-07-15

    There are controversies regarding pain expression in mentally disabled people, including Down syndrome patients. The aim of this study was to examine neuropathic pain-related behavior and peripheral nerve regeneration in mouse model of Down syndrome. Sciatic nerves of double transgenic mice, overexpressing both amyloid precursor protein (APP) and Cu/Zn superoxide dismutase (SOD1) genes, and FVB/N wild type mice were transected and immediately resutured. Evaluation of autotomy and functional recovery was carried out during 4-week follow-up. We found markedly less severe autotomy in transgenic animals, although the onset of autotomy was significantly delayed in control mice. Interestingly, neuroma formation at the injury site was significantly more prominent in transgenic animals. Sciatic function index outcome was better in transgenic mice than in wild-type group. Histological evaluation revealed no statistically significant differences in the number of GAP-43-positive growth cones and macrophages in the distal stump of the transected nerve between groups. However, in transgenic animals, the regenerating axons were arranged more chaotically. The number of Schwann cells in the distal stump of the transected nerves was significantly lower in transgenic mice. The number of surviving motoneurons was markedly decreased in transgenic group. We measured also the atrophy of denervated muscles and found it decreased in APP/SOD1 overexpressing mice. Taken together, in this model of Down syndrome, we observed increased neuroma formation and decreased autotomy after peripheral nerve injury. Our findings suggest that APP/SOD1 overexpressing mice are less sensitive for neuropathic pain associated with neuroma. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Prognostic implication of aquaporin 1 overexpression in resected lung adenocarcinoma.

    Science.gov (United States)

    Bellezza, Guido; Vannucci, Jacopo; Bianconi, Fortunato; Metro, Giulio; Del Sordo, Rachele; Andolfi, Marco; Ferri, Ivana; Siccu, Paola; Ludovini, Vienna; Puma, Francesco; Sidoni, Angelo; Cagini, Lucio

    2017-12-01

    Aquaporins (AQPs) are a group of transmembrane water-selective channel proteins thought to play a role in the regulation of water permeability for plasma membranes. Indeed, high AQP levels have been suggested to promote the progression, invasion and metastasis of tumours. Specifically, AQP1 and AQP5 overexpression in lung adenocarcinoma (AC) have been suggested to be involved in molecular mechanisms in lung cancer. The aim of this retrospective cohort single-centre study was to assess both the levels of expression and therein the prognostic significance, regarding outcome of AQP1 and AQP5 in resected AC patients. Patients with histological diagnoses of lung AC submitted to pulmonary resection were included in this cohort study. Tissue microarrays containing cores from 185 ACs were prepared. AQP1 and AQP5 expressions were assessed by immunohistochemistry. Results were scored as either low (Score 0-2) or high (Score 3-9). Clinical data, pathological tumour-node-metastasis staging and follow-up were recorded. Multivariate Cox survival analysis and Fisher's t-test were performed. AQP1 overexpression was detected in 85 (46%) patients, while AQP5 overexpression was observed in 45 (24%) patients. AQP1 did not result being significantly correlated with clinical and pathological parameters, while AQP5 resulted more expressed in AC with mucinous and papillary predominant patterns. Patients with AQP1 overexpression had shorter disease-free survival (P = 0.001) compared with patients without AQP1 overexpression. Multivariate analysis confirmed that AQP1 overexpression was significantly associated with shorter disease-free survival (P = 0.001). Our results evidenced that AQP1 overexpression resulted in a shorter disease-free survival in lung AC patients. Being so, AQP1 overexpression might be an important prognostic marker in lung AC. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights

  9. Tobacco, alcohol, and p53 overexpression in early colorectal neoplasia

    International Nuclear Information System (INIS)

    Terry, Mary Beth; Neugut, Alfred I; Mansukhani, Mahesh; Waye, Jerome; Harpaz, Noam; Hibshoosh, Hanina

    2003-01-01

    The p53 tumor suppressor gene is commonly mutated in colorectal cancer. While the effect of p53 mutations on colorectal cancer prognosis has been heavily studied, less is known about how epidemiologic risk factors relate to p53 status, particularly in early colorectal neoplasia prior to clinically invasive colorectal cancer (including adenomas, carcinoma in situ (CIS), and intramucosal carcinoma). We examined p53 status, as measured by protein overexpression, in 157 cases with early colorectal neoplasia selected from three New York City colonoscopy clinics. After collecting paraffin-embedded tissue blocks, immunohistochemistry was performed using an anti-p53 monoclonal mouse IgG 2 a [BP53-12-1] antibody. We analyzed whether p53 status was different for risk factors for colorectal neoplasia relative to a polyp-free control group (n = 508). p53 overexpression was found in 10.3%, 21.7%, and 34.9%, of adenomatous polyps, CIS, and intramucosal cases, respectively. Over 90% of the tumors with p53 overexpression were located in the distal colon and rectum. Heavy cigarette smoking (30+ years) was associated with cases not overexpressing p53 (OR = 1.8, 95% CI = 1.1–2.9) but not with those cases overexpressing p53 (OR = 1.0, 95% CI = 0.4–2.6). Heavy beer consumption (8+ bottles per week) was associated with cases overexpressing p53 (OR = 4.0, 95% CI = 1.3–12.0) but not with cases without p53 overexpression (OR = 1.6, 95% CI = 0.7–3.7). Our findings that p53 overexpression in early colorectal neoplasia may be positively associated with alcohol intake and inversely associated with cigarette smoking are consistent with those of several studies of p53 expression and invasive cancer, and suggest that there may be relationships of smoking and alcohol with p53 early in the adenoma to carcinoma sequence

  10. Transgenic overexpression of ADAM12 suppresses muscle regeneration and aggravates dystrophy in aged mdx mice

    DEFF Research Database (Denmark)

    Jørgensen, Louise Helskov; Jensen, Charlotte Harken; Wewer, Ulla M

    2007-01-01

    mice (ADAM12(+)) after a knife cut lesion and observed that the regeneration process was significantly impaired. ADAM12 seemed to inhibit the satellite cell response and delay myoblast differentiation. These results discourage long-term therapeutic use of ADAM12. They also point to impaired...... effect of ADAM12 was suggested to be mediated via a membrane-stabilizing up-regulation of utrophin, alpha7B integrin, and dystroglycans. Ectopic ADAM12 expression in normal mouse skeletal muscle also improved regeneration after freeze injury, presumably by the same mechanism. Hence, it was suggested...... overexpressing ADAM12 (ADAM12(+)/mdx mice), even though their utrophin levels were mildly elevated compared with age-matched controls. Thus, membrane stabilization was not sufficient to provide protection during prolonged disease. Consequently, we reinvestigated skeletal muscle regeneration in ADAM12 transgenic...

  11. Location Estimation using Delayed Measurements

    DEFF Research Database (Denmark)

    Bak, Martin; Larsen, Thomas Dall; Nørgård, Peter Magnus

    1998-01-01

    When combining data from various sensors it is vital to acknowledge possible measurement delays. Furthermore, the sensor fusion algorithm, often a Kalman filter, should be modified in order to handle the delay. The paper examines different possibilities for handling delays and applies a new techn...... technique to a sensor fusion system for estimating the location of an autonomous guided vehicle. The system fuses encoder and vision measurements in an extended Kalman filter. Results from experiments in a real environment are reported...

  12. Overexpression of AtLOV1 in Switchgrass alters plant architecture, lignin content, and flowering time.

    Directory of Open Access Journals (Sweden)

    Bin Xu

    Full Text Available BACKGROUND: Switchgrass (Panicum virgatum L. is a prime candidate crop for biofuel feedstock production in the United States. As it is a self-incompatible polyploid perennial species, breeding elite and stable switchgrass cultivars with traditional breeding methods is very challenging. Translational genomics may contribute significantly to the genetic improvement of switchgrass, especially for the incorporation of elite traits that are absent in natural switchgrass populations. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we constitutively expressed an Arabidopsis NAC transcriptional factor gene, LONG VEGETATIVE PHASE ONE (AtLOV1, in switchgrass. Overexpression of AtLOV1 in switchgrass caused the plants to have a smaller leaf angle by changing the morphology and organization of epidermal cells in the leaf collar region. Also, overexpression of AtLOV1 altered the lignin content and the monolignol composition of cell walls, and caused delayed flowering time. Global gene-expression analysis of the transgenic plants revealed an array of responding genes with predicted functions in plant development, cell wall biosynthesis, and flowering. CONCLUSIONS/SIGNIFICANCE: To our knowledge, this is the first report of a single ectopically expressed transcription factor altering the leaf angle, cell wall composition, and flowering time of switchgrass, therefore demonstrating the potential advantage of translational genomics for the genetic improvement of this crop.

  13. Modeling delay in genetic networks: from delay birth-death processes to delay stochastic differential equations.

    Science.gov (United States)

    Gupta, Chinmaya; López, José Manuel; Azencott, Robert; Bennett, Matthew R; Josić, Krešimir; Ott, William

    2014-05-28

    Delay is an important and ubiquitous aspect of many biochemical processes. For example, delay plays a central role in the dynamics of genetic regulatory networks as it stems from the sequential assembly of first mRNA and then protein. Genetic regulatory networks are therefore frequently modeled as stochastic birth-death processes with delay. Here, we examine the relationship between delay birth-death processes and their appropriate approximating delay chemical Langevin equations. We prove a quantitative bound on the error between the pathwise realizations of these two processes. Our results hold for both fixed delay and distributed delay. Simulations demonstrate that the delay chemical Langevin approximation is accurate even at moderate system sizes. It captures dynamical features such as the oscillatory behavior in negative feedback circuits, cross-correlations between nodes in a network, and spatial and temporal information in two commonly studied motifs of metastability in biochemical systems. Overall, these results provide a foundation for using delay stochastic differential equations to approximate the dynamics of birth-death processes with delay.

  14. Modeling delay in genetic networks: From delay birth-death processes to delay stochastic differential equations

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Chinmaya; López, José Manuel; Azencott, Robert; Ott, William [Department of Mathematics, University of Houston, Houston, Texas 77004 (United States); Bennett, Matthew R. [Department of Biochemistry and Cell Biology, Rice University, Houston, Texas 77204, USA and Institute of Biosciences and Bioengineering, Rice University, Houston, Texas 77005 (United States); Josić, Krešimir [Department of Mathematics, University of Houston, Houston, Texas 77004 (United States); Department of Biology and Biochemistry, University of Houston, Houston, Texas 77204 (United States)

    2014-05-28

    Delay is an important and ubiquitous aspect of many biochemical processes. For example, delay plays a central role in the dynamics of genetic regulatory networks as it stems from the sequential assembly of first mRNA and then protein. Genetic regulatory networks are therefore frequently modeled as stochastic birth-death processes with delay. Here, we examine the relationship between delay birth-death processes and their appropriate approximating delay chemical Langevin equations. We prove a quantitative bound on the error between the pathwise realizations of these two processes. Our results hold for both fixed delay and distributed delay. Simulations demonstrate that the delay chemical Langevin approximation is accurate even at moderate system sizes. It captures dynamical features such as the oscillatory behavior in negative feedback circuits, cross-correlations between nodes in a network, and spatial and temporal information in two commonly studied motifs of metastability in biochemical systems. Overall, these results provide a foundation for using delay stochastic differential equations to approximate the dynamics of birth-death processes with delay.

  15. Modeling delay in genetic networks: From delay birth-death processes to delay stochastic differential equations

    International Nuclear Information System (INIS)

    Gupta, Chinmaya; López, José Manuel; Azencott, Robert; Ott, William; Bennett, Matthew R.; Josić, Krešimir

    2014-01-01

    Delay is an important and ubiquitous aspect of many biochemical processes. For example, delay plays a central role in the dynamics of genetic regulatory networks as it stems from the sequential assembly of first mRNA and then protein. Genetic regulatory networks are therefore frequently modeled as stochastic birth-death processes with delay. Here, we examine the relationship between delay birth-death processes and their appropriate approximating delay chemical Langevin equations. We prove a quantitative bound on the error between the pathwise realizations of these two processes. Our results hold for both fixed delay and distributed delay. Simulations demonstrate that the delay chemical Langevin approximation is accurate even at moderate system sizes. It captures dynamical features such as the oscillatory behavior in negative feedback circuits, cross-correlations between nodes in a network, and spatial and temporal information in two commonly studied motifs of metastability in biochemical systems. Overall, these results provide a foundation for using delay stochastic differential equations to approximate the dynamics of birth-death processes with delay

  16. Overexpression of Enterococcus faecalis elr operon protects from phagocytosis.

    Science.gov (United States)

    Cortes-Perez, Naima G; Dumoulin, Romain; Gaubert, Stéphane; Lacoux, Caroline; Bugli, Francesca; Martin, Rebeca; Chat, Sophie; Piquand, Kevin; Meylheuc, Thierry; Langella, Philippe; Sanguinetti, Maurizio; Posteraro, Brunella; Rigottier-Gois, Lionel; Serror, Pascale

    2015-05-25

    Mechanisms underlying the transition from commensalism to virulence in Enterococcus faecalis are not fully understood. We previously identified the enterococcal leucine-rich protein A (ElrA) as a virulence factor of E. faecalis. The elrA gene is part of an operon that comprises four other ORFs encoding putative surface proteins of unknown function. In this work, we compared the susceptibility to phagocytosis of three E. faecalis strains, including a wild-type (WT), a ΔelrA strain, and a strain overexpressing the whole elr operon in order to understand the role of this operon in E. faecalis virulence. While both WT and ΔelrA strains were efficiently phagocytized by RAW 264.7 mouse macrophages, the elr operon-overexpressing strain showed a decreased capability to be internalized by the phagocytic cells. Consistently, the strain overexpressing elr operon was less adherent to macrophages than the WT strain, suggesting that overexpression of the elr operon could confer E. faecalis with additional anti-adhesion properties. In addition, increased virulence of the elr operon-overexpressing strain was shown in a mouse peritonitis model. Altogether, our results indicate that overexpression of the elr operon facilitates the E. faecalis escape from host immune defenses.

  17. Systematic of delayed neutron parameters

    International Nuclear Information System (INIS)

    Isaev, S.G.; Piksaikin, V.M.

    2000-01-01

    The experimental studies of the energy dependence of the delayed neutron (DN) parameters for various fission systems has shown that the behaviour of a some combination of delayed neutron parameters has a similar features. On the basis of this findings the systematics of delayed neutron experimental data for thorium, uranium, plutonium and americium isotopes have been investigated with the purpose to find a correlation of DN parameters with characteristics of fissioning system as well as a correlation between the delayed neutron parameters themselves. It was presented the preliminary results which were obtained during study the physics interpretation of the results [ru

  18. Time Delay of CGM Sensors

    Science.gov (United States)

    Schmelzeisen-Redeker, Günther; Schoemaker, Michael; Kirchsteiger, Harald; Freckmann, Guido; Heinemann, Lutz; del Re, Luigi

    2015-01-01

    Background: Continuous glucose monitoring (CGM) is a powerful tool to support the optimization of glucose control of patients with diabetes. However, CGM systems measure glucose in interstitial fluid but not in blood. Rapid changes in one compartment are not accompanied by similar changes in the other, but follow with some delay. Such time delays hamper detection of, for example, hypoglycemic events. Our aim is to discuss the causes and extent of time delays and approaches to compensate for these. Methods: CGM data were obtained in a clinical study with 37 patients with a prototype glucose sensor. The study was divided into 5 phases over 2 years. In all, 8 patients participated in 2 phases separated by 8 months. A total number of 108 CGM data sets including raw signals were used for data analysis and were processed by statistical methods to obtain estimates of the time delay. Results: Overall mean (SD) time delay of the raw signals with respect to blood glucose was 9.5 (3.7) min, median was 9 min (interquartile range 4 min). Analysis of time delays observed in the same patients separated by 8 months suggests a patient dependent delay. No significant correlation was observed between delay and anamnestic or anthropometric data. The use of a prediction algorithm reduced the delay by 4 minutes on average. Conclusions: Prediction algorithms should be used to provide real-time CGM readings more consistent with simultaneous measurements by SMBG. Patient specificity may play an important role in improving prediction quality. PMID:26243773

  19. Inhibition of G1-phase arrest induced by ionizing radiation in hematopoietic cells by overexpression of genes involved in the G1/S-phase transition

    International Nuclear Information System (INIS)

    Epperly, M.; Berry, L.; Halloran, A.; Greenberger, J.S.

    1995-01-01

    D-type cyclins and cyclin-dependent kinase (cdk-4) are likely involved in regulating passage of cells through the G 1 phase of the cell cycle. A decrease in the proportion of cells in G 1 , a relatively radiation-sensitive phase of the cell cycle, should result in increased resistance to ionizing radiation; however, the effect of such overexpression on X-ray-induced G 1 -phase arrest is not known. Radiation survival curves were obtained at a dose rate of either 8 cGy/min or 1 Gy/min for subclones of the IL-3-dependent hematopoietic progenitor cell line 32D cl 3 expressing transgenes for either cyclin-D1, D2 or D3 or cdk-4. We compared the results to those with overexpression of the transgene for Bcl-2, whose expression enhances radiation survival and delays apoptosis. Cells overexpressing transgenes for each D-type cyclin or Bcl-2 had an increased number of cells in S phase compared to parent line 32D cl 3; however, overexpression of cdk-4 had no effect on cell cycle distribution. Cell death resulting from withdrawal of IL-3 was not affected by overexpression of D2, cdk-4 or Bcl-2. Flow cytometry 24 h after 5 Gy irradiation demonstrated that overexpression of each G 1 -phase regulatory transgene decreased the proportion of cells at the G 1 /S-phase border. Western analysis revealed induction of cyclin-D protein levels by irradiation, but no change in the D O , but a significant increase in the rvec n for cyclin-D or cdk-4 transgene-overexpressing clones at 1 Gy/min (P 1 /S-phase arrest. 31 refs., 4 figs., 4 tabs

  20. Delayed Auditory Feedback and Movement

    Science.gov (United States)

    Pfordresher, Peter Q.; Dalla Bella, Simone

    2011-01-01

    It is well known that timing of rhythm production is disrupted by delayed auditory feedback (DAF), and that disruption varies with delay length. We tested the hypothesis that disruption depends on the state of the movement trajectory at the onset of DAF. Participants tapped isochronous rhythms at a rate specified by a metronome while hearing DAF…

  1. #FakeNobelDelayReasons

    CERN Multimedia

    2013-01-01

    Tuesday’s hour-long delay of the Nobel Prize in Physics announcement was (and still is) quite the cause for speculation. But on the Twittersphere, it was simply the catalyst for some fantastic puns, so-bad-they're-good physics jokes and other shenanigans. Here are some of our favourite #FakeNobelDelayReasons.    

  2. Picosecond resolution programmable delay line

    International Nuclear Information System (INIS)

    Suchenek, Mariusz

    2009-01-01

    The note presents implementation of a programmable delay line for digital signals. The tested circuit has a subnanosecond delay range programmable with a resolution of picoseconds. Implementation of the circuit was based on low-cost components, easily available on the market. (technical design note)

  3. HER2 amplification, overexpression and score criteria in esophageal adenocarcinoma

    Science.gov (United States)

    Hu, Yingchuan; Bandla, Santhoshi; Godfrey, Tony E.; Tan, Dongfeng; Luketich, James D.; Pennathur, Arjun; Qiu, Xing; Hicks, David G.; Peters, Jeffrey; Zhou, Zhongren

    2011-01-01

    The HER2 oncogene was recently reported to be amplified and overexpressed in esophageal adenocarcinoma. However, the relationship of HER2 amplification in esophageal adenocarcinoma with prognosis has not been well defined. The scoring systems for clinically evaluating HER2 in esophageal adenocarcinoma are not established. The aims of the study were to establish a HER2 scoring system and comprehensively investigate HER2 amplification and overexpression in esophageal adenocarcinoma and its precursor lesion. Using a tissue microarray, containing 116 cases of esophageal adenocarcinoma, 34 cases of BE, 18 cases of low grade dysplasia and 15 cases of high grade dysplasia, HER2 amplification and overexpression were analyzed by HercepTest and CISH methods. The amplification frequency in an independent series of 116 esophageal adenocarcinoma samples was also analyzed using Affymetrix SNP 6.0 microarrays. In our studies, we have found that HER2 amplification does not associate with poor prognosis in total 232 esophageal adenocarcinoma patients by CISH and high density microarrays. We further confirm the similar frequency of HER2 amplification by CISH (18.10%; 21/116) and SNP 6.0 microarrays (16.4%, 19/116) in esophageal adenocarcinoma. HER2 protein overexpression was observed in 12.1 % (14/116) of esophageal adenocarcinoma and 6.67% (1/15) of HGD. No HER2 amplification or overexpression was identified in BE or LGD. All HER2 protein overexpression cases showed HER2 gene amplification. Gene amplification was found to be more frequent by CISH than protein overexpression in esophageal adenocarcinoma (18.10% vs 12.9%). A modified two-step model for esophageal adenocarcinoma HER-2 testing is recommend for clinical esophageal adenocarcinoma HER-2 trial. PMID:21460800

  4. Project delay analysis of HRSG

    Science.gov (United States)

    Silvianita; Novega, A. S.; Rosyid, D. M.; Suntoyo

    2017-08-01

    Completion of HRSG (Heat Recovery Steam Generator) fabrication project sometimes is not sufficient with the targeted time written on the contract. The delay on fabrication process can cause some disadvantages for fabricator, including forfeit payment, delay on HRSG construction process up until HRSG trials delay. In this paper, the author is using semi quantitative on HRSG pressure part fabrication delay with configuration plant 1 GT (Gas Turbine) + 1 HRSG + 1 STG (Steam Turbine Generator) using bow-tie analysis method. Bow-tie analysis method is a combination from FTA (Fault tree analysis) and ETA (Event tree analysis) to develop the risk matrix of HRSG. The result from FTA analysis is use as a threat for preventive measure. The result from ETA analysis is use as impact from fabrication delay.

  5. Delayed radiation neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Nagashima, T.; Miyamoto, K.; Beppu, H.; Hirose, K.; Yamada, K. (Tokyo Metropolitan Neurological Hospital (Japan))

    1981-07-01

    A case of cervical plexus neuropathy was reported in association with chronic radio-dermatitis, myxedema with thyroid adenoma and epiglottic tumor. A 38-year-old man has noticed muscle weakness and wasting of the right shoulder girdle since age 33. A detailed history taking revealed a previous irradiation to the neck because of the cervical lymphadenopathy at age 10 (X-ray 3,000 rads), keroid skin change at age 19, obesity and edema since 26, and hoarseness at 34. Laryngoscopic examination revealed a tumor on the right vocal cord, diagnosed as benign papilloma by histological study. In addition, there were chronic radio-dermatitis around the neck, primary hypothyroidism with a benign functioning adenoma on the right lobe of the thyroid, the right phrenic nerve palsy and the right recurrent nerve palsy. All these lesions were considered to be the late sequellae of radiation to the neck in childhood. Other neurological signs were weakness and amyotrophy of the right shoulder girdle with patchy sensory loss, and areflexia of the right arm. Gross power was fairly well preserved in the right hand. EMG showed neurogenic changes in the tested muscles, suggesting a peripheral nerve lesion. Nerve conduction velocities were normal. No abnormal findings were revealed by myelography and spinal CT. The neurological findings of the patient were compatible with the diagnosis of middle cervical plexus palsy apparently due to late radiation effect. In the literature eight cases of post-radiation neuropathy with a long latency have been reported. The present case with the longest latency after the radiation should be included in the series of the reported cases of ''delayed radiation neuropathy.'' (author).

  6. Delayed radiation neuropathy

    International Nuclear Information System (INIS)

    Nagashima, Toshiko; Miyamoto, Kazuto; Beppu, Hirokuni; Hirose, Kazuhiko; Yamada, Katsuhiro

    1981-01-01

    A case of cervical plexus neuropathy was reported in association with chronic radio-dermatitis, myxedema with thyroid adenoma and epiglottic tumor. A 38-year-old man has noticed muscle weakness and wasting of the right shoulder girdle since age 33. A detailed history taking revealed a previous irradiation to the neck because of the cervical lymphadenopathy at age 10 (X-ray 3,000 rads), keroid skin change at age 19, obesity and edema since 26, and hoarseness at 34. Laryngoscopic examination revealed a tumor on the right vocal cord, diagnosed as benign papilloma by histological study. In addition, there were chronic radio-dermatitis around the neck, primary hypothyroidism with a benign functioning adenoma on the right lobe of the thyroid, the right phrenic nerve palsy and the right recurrent nerve palsy. All these lesions were considered to be the late sequellae of radiation to the neck in childhood. Other neurological signs were weakness and amyotrophy of the right shoulder girdle with patchy sensory loss, and areflexia of the right arm. Gross power was fairly well preserved in the right hand. EMG showed neurogenic changes in the tested muscles, suggesting a peripheral nerve lesion. Nerve conduction velocities were normal. No abnormal findings were revealed by myelography and spinal CT. The neurological findings of the patient were compatible with the diagnosis of middle cervical plexus palsy apparently due to late radiation effect. In the literature eight cases of post-radiation neuropathy with a long latency have been reported. The present case with the longest latency after the radiation should be included in the series of the reported cases of ''delayed radiation neuropathy.'' (author)

  7. Targeted overexpression of amelotin disrupts the microstructure of dental enamel.

    Science.gov (United States)

    Lacruz, Rodrigo S; Nakayama, Yohei; Holcroft, James; Nguyen, Van; Somogyi-Ganss, Eszter; Snead, Malcolm L; White, Shane N; Paine, Michael L; Ganss, Bernhard

    2012-01-01

    We have previously identified amelotin (AMTN) as a novel protein expressed predominantly during the late stages of dental enamel formation, but its role during amelogenesis remains to be determined. In this study we generated transgenic mice that produce AMTN under the amelogenin (Amel) gene promoter to study the effect of AMTN overexpression on enamel formation in vivo. The specific overexpression of AMTN in secretory stage ameloblasts was confirmed by Western blot and immunohistochemistry. The gross histological appearance of ameloblasts or supporting cellular structures as well as the expression of the enamel proteins amelogenin (AMEL) and ameloblastin (AMBN) was not altered by AMTN overexpression, suggesting that protein production, processing and secretion occurred normally in transgenic mice. The expression of Odontogenic, Ameloblast-Associated (ODAM) was slightly increased in secretory stage ameloblasts of transgenic animals. The enamel in AMTN-overexpressing mice was much thinner and displayed a highly irregular surface structure compared to wild type littermates. Teeth of transgenic animals underwent rapid attrition due to the brittleness of the enamel layer. The microstructure of enamel, normally a highly ordered arrangement of hydroxyapatite crystals, was completely disorganized. Tomes' process, the hallmark of secretory stage ameloblasts, did not form in transgenic mice. Collectively our data demonstrate that the overexpression of amelotin has a profound effect on enamel structure by disrupting the formation of Tomes' process and the orderly growth of enamel prisms.

  8. Targeted overexpression of amelotin disrupts the microstructure of dental enamel.

    Directory of Open Access Journals (Sweden)

    Rodrigo S Lacruz

    Full Text Available We have previously identified amelotin (AMTN as a novel protein expressed predominantly during the late stages of dental enamel formation, but its role during amelogenesis remains to be determined. In this study we generated transgenic mice that produce AMTN under the amelogenin (Amel gene promoter to study the effect of AMTN overexpression on enamel formation in vivo. The specific overexpression of AMTN in secretory stage ameloblasts was confirmed by Western blot and immunohistochemistry. The gross histological appearance of ameloblasts or supporting cellular structures as well as the expression of the enamel proteins amelogenin (AMEL and ameloblastin (AMBN was not altered by AMTN overexpression, suggesting that protein production, processing and secretion occurred normally in transgenic mice. The expression of Odontogenic, Ameloblast-Associated (ODAM was slightly increased in secretory stage ameloblasts of transgenic animals. The enamel in AMTN-overexpressing mice was much thinner and displayed a highly irregular surface structure compared to wild type littermates. Teeth of transgenic animals underwent rapid attrition due to the brittleness of the enamel layer. The microstructure of enamel, normally a highly ordered arrangement of hydroxyapatite crystals, was completely disorganized. Tomes' process, the hallmark of secretory stage ameloblasts, did not form in transgenic mice. Collectively our data demonstrate that the overexpression of amelotin has a profound effect on enamel structure by disrupting the formation of Tomes' process and the orderly growth of enamel prisms.

  9. Enhanced tethered-flight duration and locomotor activity by overexpression of the human gene SOD1 in Drosophila motorneurons

    Directory of Open Access Journals (Sweden)

    Agavni Petrosyan

    2015-03-01

    Full Text Available Mutation of the human gene superoxide dismutase (hSOD1 is associated with the fatal neurodegenerative disease familial amyotrophic lateral sclerosis (Lou Gehrig’s disease. Selective overexpression of hSOD1 in Drosophila motorneurons increases lifespan to 140% of normal. The current study was designed to determine resistance to lifespan decline and failure of sensorimotor functions by overexpressing hSOD1 in Drosophila‘s motorneurons. First, we measured the ability to maintain continuous flight and wingbeat frequency (WBF as a function of age (5 to 50 days. Flies overexpressing hSOD1 under the D42-GAL4 activator were able to sustain flight significantly longer than controls, with the largest effect observed in the middle stages of life. The hSOD1-expressed line also had, on average, slower wingbeat frequencies in late, but not early life relative to age-matched controls. Second, we examined locomotor (exploratory walking behavior in late life when flies had lost the ability to fly (age ≥ 60 d. hSOD1-expressed flies showed significantly more robust walking activity relative to controls. Findings show patterns of functional decline dissimilar to those reported for other life-extended lines, and suggest that the hSOD1 gene not only delays death but enhances sensorimotor abilities critical to survival even in late life.

  10. Attosecond Delays in Molecular Photoionization.

    Science.gov (United States)

    Huppert, Martin; Jordan, Inga; Baykusheva, Denitsa; von Conta, Aaron; Wörner, Hans Jakob

    2016-08-26

    We report measurements of energy-dependent photoionization delays between the two outermost valence shells of N_{2}O and H_{2}O. The combination of single-shot signal referencing with the use of different metal foils to filter the attosecond pulse train enables us to extract delays from congested spectra. Remarkably large delays up to 160 as are observed in N_{2}O, whereas the delays in H_{2}O are all smaller than 50 as in the photon-energy range of 20-40 eV. These results are interpreted by developing a theory of molecular photoionization delays. The long delays measured in N_{2}O are shown to reflect the population of molecular shape resonances that trap the photoelectron for a duration of up to ∼110 as. The unstructured continua of H_{2}O result in much smaller delays at the same photon energies. Our experimental and theoretical methods make the study of molecular attosecond photoionization dynamics accessible.

  11. Prognostic implication of NQO1 overexpression in hepatocellular carcinoma.

    Science.gov (United States)

    Lin, Lijuan; Sun, Jie; Tan, Yan; Li, Zhenling; Kong, Fanyong; Shen, Yue; Liu, Chao; Chen, Litian

    2017-11-01

    To explore the role of NQO1 overexpression for prognostic implication in hepatocellular carcinoma (HCC), NQO1 mRNA levels were detected in HCC fresh tissue samples of HCC and nontumor tissues, respectively. One hundred fifty-six cases of HCC meeting strict follow-up criteria were selected for immunohistochemical staining of NQO1 protein. Correlations between NQO1 overexpression and clinicopathological features of HCC were evaluated using χ 2 tests, survival rates were calculated using the Kaplan-Meier method, and the relationship between prognostic factors and patient 5-year survival was analyzed using Cox proportional hazards analysis. In results, the levels of NQO1 mRNA were significantly up-regulated in 14 fresh tissue samples of HCC. Immunohistochemical analysis showed that the NQO1 expression and overexpression rates were significantly higher in HCC samples compared with either adjacent nontumor tissues or normal liver tissues. NQO1 overexpression correlated to tumor size, venous infiltration and late pTNM stage of HCC. NQO1 overexpression was also related to low disease-free survival and 5-year survival rates. In the late-stage group, disease-free and 5-year survival rates of patients with NQO1 overexpression were significantly lower than those of patients without NQO1 expression. Further analysis using a Cox proportional hazards regression model revealed that NQO1 expression emerged as a significant independent hazard factor for the 5-year survival rate of patients with HCC. Therefore, NQO1 plays an important role in the progression of HCC. NQO1 may potentially be used as an independent biomarker for prognostic evaluation of HCC. Copyright © 2017. Published by Elsevier Inc.

  12. DEK protein overexpression predicts poor prognosis in pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Sun, Jie; Bi, Fangfang; Yang, Yang; Zhang, Yuan; Jin, Aihua; Li, Jinzi; Lin, Zhenhua

    2017-02-01

    DEK, a transcription factor, is involved in mRNA splicing, transcriptional control, cell division and differentiation. Recent studies suggest that DEK overexpression can promote tumorigenesis in a wide range of cancer cell types. However, little is known concerning the status of DEK in pancreatic ductal adenocarcinoma (PDAC). Based on the microarray data from Gene Expression Omnibus (GEO), the expression levels of DEK mRNA in PDAC tissues were significantly higher than levels in the adjacent non-tumor tissues. To explore the clinical features of DEK overexpression in PDAC, 87 PDAC and 52 normal pancreas tissues were selected for immunoenzyme staining of the DEK protein. Localization of the DEK protein was detected in PANC-1 pancreatic cancer cells using immunofluorescence (IF) staining. The correlations between DEK overexpression and the clinical features of PDAC were evaluated using the Chi-squared (χ2) and Fisher's exact tests. The survival rates were calculated by the Kaplan-Meier method, and the relationship between prognostic factors and patient survival was also analyzed by the Cox proportional hazard models. The expression levels of DEK mRNA in PDAC tissues were significantly higher than that in the adjacent non‑tumor tissues. The DEK protein showed a primarily nuclear staining pattern in PDAC. The positive rate of the DEK protein was 52.9% (46/87) in PDAC, which was significantly higher than that in the adjacent normal pancreatic tissues (7.7%, 4/52). DEK overexpression in PDAC was correlated with tumor size, histological grade, tumor‑node‑metastasis (TNM) stage and overall survival (OS) rates. In addition, multivariate analysis demonstrated that DEK overexpression was an independent prognostic factor along with histological grade and TNM stage in patients with PDAC. In conclusion, DEK overexpression is associated with PDAC progression and may be a potential biomarker for poor prognostic evaluation in PDAC.

  13. CD147 overexpression promotes tumorigenicity in Chinese hamster ovary cells.

    Science.gov (United States)

    Yong, Yu-Le; Liao, Cheng-Gong; Wei, Ding; Chen, Zhi-Nan; Bian, Huijie

    2016-04-01

    CD147 overexpresses in many epithelium-originated tumors and plays an important role in tumor migration and invasion. Most studies aim at the role of CD147 in tumor progression using tumor cell models. However, the influence of abnormal overexpression of CD147 on neoplastic transformation of normal cells is unknown. Here, the role of CD147 in malignant phenotype transformation in CHO cells was investigated. Three CHO cell lines that stably overexpressed CD147 (CHO-CD147), EGFP-CD147 (CHO-EGFP-CD147), and EGFP (CHO-EGFP) were generated by transfection of plasmids containing human CD147, EGFP-human CD147, and EGFP genes into CHO cells. Cell migration and invasion were detected by wound healing and transwell matrix penetration assay. Trypan blue exclusion, MTT, cell cycle analysis, and BrdU cell proliferation assay were used to detect cell viability and cell proliferation. Annexin V-FITC analysis was performed to detect apoptosis. We found that CD147 overexpression promoted the migration and invasion of CHO cells. CD147 accelerated the G1 to S phase transition and enhanced the CHO cell proliferation. Overexpression of CD147 inhibited both early- and late-stages of apoptosis of CHO-CD147 cells, which is caused by serum deprivation. CHO-EGFP-CD147 cells showed an increased anchorage-independent growth compared with CHO-EGFP cells as detected by soft-agar colony formation assay. The tumors formed by CHO-CD147 cells in nude mice were larger and coupled with higher expression of proliferating cell nuclear antigen and Ki-67 than that of CHO cells. In conclusion, human CD147 overexpression induces malignant phenotype in CHO cells. © 2015 International Federation for Cell Biology.

  14. Delays and networked control systems

    CERN Document Server

    Hetel, Laurentiu; Daafouz, Jamal; Johansson, Karl

    2016-01-01

    This edited monograph includes state-of-the-art contributions on continuous time dynamical networks with delays. The book is divided into four parts. The first part presents tools and methods for the analysis of time-delay systems with a particular attention on control problems of large scale or infinite-dimensional systems with delays. The second part of the book is dedicated to the use of time-delay models for the analysis and design of Networked Control Systems. The third part of the book focuses on the analysis and design of systems with asynchronous sampling intervals which occur in Networked Control Systems. The last part of the book exposes several contributions dealing with the design of cooperative control and observation laws for networked control systems. The target audience primarily comprises researchers and experts in the field of control theory, but the book may also be beneficial for graduate students. .

  15. Linear rotary optical delay lines

    Science.gov (United States)

    Guerboukha, Hichem; Qu, Hang; Skorobogatiy, Maksim

    2016-03-01

    We present a semi-analytical solution for the design of a high-speed rotary optical delay line that use a combination of two rotating curvilinear reflectors. We demonstrate that it is possible to design an infinite variety of the optical delay lines featuring linear dependence of the optical delay on the rotation angle. This is achieved via shape optimization of the rotating reflector surfaces. Moreover, a convenient spatial separation of the incoming and outgoing beams is possible. For the sake of example, we present blades that fit into a circle of 10cm diameter. Finally, a prototype of a rotary delay line is fabricated using CNC machining, and its optical properties are characterized.

  16. Over-expression of Trxo1 increases the viability of tobacco BY-2 cells under H2O2 treatment.

    Science.gov (United States)

    Ortiz-Espín, Ana; Locato, Vittoria; Camejo, Daymi; Schiermeyer, Andreas; De Gara, Laura; Sevilla, Francisca; Jiménez, Ana

    2015-09-01

    Reactive oxygen species (ROS), especially hydrogen peroxide, play a critical role in the regulation of plant development and in the induction of plant defence responses during stress adaptation, as well as in plant cell death. The antioxidant system is responsible for controlling ROS levels in these processes but redox homeostasis is also a key factor in plant cell metabolism under normal and stress situations. Thioredoxins (Trxs) are ubiquitous small proteins found in different cell compartments, including mitochondria and nuclei (Trxo1), and are involved in the regulation of target proteins through reduction of disulphide bonds, although their role under oxidative stress has been less well studied. This study describes over-expression of a Trxo1 for the first time, using a cell-culture model subjected to an oxidative treatment provoked by H2O2. Control and over-expressing PsTrxo1 tobacco (Nicotiana tabacum) BY-2 cells were treated with 35 mm H2O2 and the effects were analysed by studying the growth dynamics of the cultures together with oxidative stress parameters, as well as several components of the antioxidant systems involved in the metabolism of H2O2. Analysis of different hallmarks of programmed cell death was also carried out. Over-expression of PsTrxo1 caused significant differences in the response of TBY-2 cells to high concentrations of H2O2, namely higher and maintained viability in over-expressing cells, whilst the control line presented a severe decrease in viability and marked indications of oxidative stress, with generalized cell death after 3 d of treatment. In over-expressing cells, an increase in catalase activity, decreases in H2O2 and nitric oxide contents and maintenance of the glutathione redox state were observed. A decreased content of endogenous H2O2 may be responsible in part for the delayed cell death found in over-expressing cells, in which changes in oxidative parameters and antioxidants were less extended after the oxidative

  17. Systematics in delayed neutron yields

    Energy Technology Data Exchange (ETDEWEB)

    Ohsawa, Takaaki [Kinki Univ., Higashi-Osaka, Osaka (Japan). Atomic Energy Research Inst.

    1998-03-01

    An attempt was made to reproduce the systematic trend observed in the delayed neutron yields for actinides on the basis of the five-Gaussian representation of the fission yield together with available data sets for delayed neutron emission probability. It was found that systematic decrease in DNY for heavier actinides is mainly due to decrease of fission yields of precursors in the lighter side of the light fragment region. (author)

  18. Analytical applications for delayed neutrons

    International Nuclear Information System (INIS)

    Eccleston, G.W.

    1983-01-01

    Analytical formulations that describe the time dependence of neutron populations in nuclear materials contain delayed-neutron dependent terms. These terms are important because the delayed neutrons, even though their yields in fission are small, permit control of the fission chain reaction process. Analytical applications that use delayed neutrons range from simple problems that can be solved with the point reactor kinetics equations to complex problems that can only be solved with large codes that couple fluid calculations with the neutron dynamics. Reactor safety codes, such as SIMMER, model transients of the entire reactor core using coupled space-time neutronics and comprehensive thermal-fluid dynamics. Nondestructive delayed-neutron assay instruments are designed and modeled using a three-dimensional continuous-energy Monte Carlo code. Calculations on high-burnup spent fuels and other materials that contain a mix of uranium and plutonium isotopes require accurate and complete information on the delayed-neutron periods, yields, and energy spectra. A continuing need exists for delayed-neutron parameters for all the fissioning isotopes

  19. Lung disease phenotypes caused by overexpression of combinations of α-, β-, and γ-subunits of the epithelial sodium channel in mouse airways.

    Science.gov (United States)

    Livraghi-Butrico, Alessandra; Wilkinson, Kristen J; Volmer, Allison S; Gilmore, Rodney C; Rogers, Troy D; Caldwell, Ray A; Burns, Kimberlie A; Esther, Charles R; Mall, Marcus A; Boucher, Richard C; O'Neal, Wanda K; Grubb, Barbara R

    2018-02-01

    The epithelial Na + channel (ENaC) regulates airway surface hydration. In mouse airways, ENaC is composed of three subunits, α, β, and γ, which are differentially expressed (α > β > γ). Airway-targeted overexpression of the β subunit results in Na + hyperabsorption, causing airway surface dehydration, hyperconcentrated mucus with delayed clearance, lung inflammation, and perinatal mortality. Notably, mice overexpressing the α- or γ-subunit do not exhibit airway Na + hyperabsorption or lung pathology. To test whether overexpression of multiple ENaC subunits produced Na + transport and disease severity exceeding that of βENaC-Tg mice, we generated double (αβ, αγ, βγ) and triple (αβγ) transgenic mice and characterized their lung phenotypes. Double αγENaC-Tg mice were indistinguishable from WT littermates. In contrast, double βγENaC-Tg mice exhibited airway Na + absorption greater than that of βENaC-Tg mice, which was paralleled by worse survival, decreased mucociliary clearance, and more severe lung pathology. Double αβENaC-Tg mice exhibited Na + transport rates comparable to those of βENaC-Tg littermates. However, αβENaC-Tg mice had poorer survival and developed severe parenchymal consolidation. In situ hybridization (RNAscope) analysis revealed both alveolar and airway αENaC-Tg overexpression. Triple αβγENaC-Tg mice were born in Mendelian proportions but died within the first day of life, and the small sample size prevented analyses of cause(s) of death. Cumulatively, these results indicate that overexpression of βENaC is rate limiting for generation of pathological airway surface dehydration. Notably, airway co-overexpression of β- and γENaC had additive effects on Na + transport and disease severity, suggesting dose dependency of these two variables.

  20. Overexpression of Adenylyl Cyclase Encoded by the Mycobacterium tuberculosis Rv2212 Gene Confers Improved Fitness, Accelerated Recovery from Dormancy and Enhanced Virulence in Mice

    Directory of Open Access Journals (Sweden)

    Margarita O. Shleeva

    2017-08-01

    Full Text Available Earlier we demonstrated that the adenylyl cyclase (AC encoded by the MSMEG_4279 gene plays a key role in the resuscitation and growth of dormant Mycobacterium smegmatis and that overexpression of this gene leads to an increase in intracellular cAMP concentration and prevents the transition of M. smegmatis from active growth to dormancy in an extended stationary phase accompanied by medium acidification. We surmised that the homologous Rv2212 gene of M. tuberculosis (Mtb, the main cAMP producer, plays similar physiological roles by supporting, under these conditions, the active state and reactivation of dormant bacteria. To test this hypothesis, we established Mtb strain overexpressing Rv2212 and compared its in vitro and in vivo growth characteristics with a control strain. In vitro, the AC-overexpressing pMindRv2212 strain demonstrated faster growth in a liquid medium, prolonged capacity to form CFUs and a significant delay or even prevention of transition toward dormancy. AC-overexpressing cells exhibited easier recovery from dormancy. In vivo, AC-overexpressing bacteria demonstrated significantly higher growth rates (virulence in the lungs and spleens of infected mice compared to the control strain, and, unlike the latter, killed mice in the TB-resistant strain before month 8 of infection. Even in the absence of selecting hygromycin B, all pMindRv2212 CFUs retained the Rv2212 insert during in vivo growth, strongly suggesting that AC overexpression is beneficial for bacteria. Taken together, our results indicate that cAMP supports the maintenance of Mtb cells vitality under unfavorable conditions in vitro and their virulence in vivo.

  1. Control of cellulose biosynthesis by overexpression of a transcription factor

    Energy Technology Data Exchange (ETDEWEB)

    Han, Kyung-Hwan; Ko, Jae-Heung; Kim, Won-Chan; Kim; , Joo-Yeol

    2017-05-16

    The invention relates to the over-expression of a transcription factor selected from the group consisting of MYB46, HAM1, HAM2, MYB112, WRKY11, ERF6, and any combination thereof in a plant, which can modulate and thereby modulating the cellulose content of the plant.

  2. APRIL is overexpressed in cancer: link with tumor progression

    International Nuclear Information System (INIS)

    Moreaux, Jérôme; Veyrune, Jean-Luc; De Vos, John; Klein, Bernard

    2009-01-01

    BAFF and APRIL share two receptors – TACI and BCMA – and BAFF binds to a third receptor, BAFF-R. Increased expression of BAFF and APRIL is noted in hematological malignancies. BAFF and APRIL are essential for the survival of normal and malignant B lymphocytes, and altered expression of BAFF or APRIL or of their receptors (BCMA, TACI, or BAFF-R) have been reported in various B-cell malignancies including B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Hodgkin's lymphoma, multiple myeloma, and Waldenstrom's macroglobulinemia. We compared the expression of BAFF, APRIL, TACI and BAFF-R gene expression in 40 human tumor types – brain, epithelial, lymphoid, germ cells – to that of their normal tissue counterparts using publicly available gene expression data, including the Oncomine Cancer Microarray database. We found significant overexpression of TACI in multiple myeloma and thyroid carcinoma and an association between TACI expression and prognosis in lymphoma. Furthermore, BAFF and APRIL are overexpressed in many cancers and we show that APRIL expression is associated with tumor progression. We also found overexpression of at least one proteoglycan with heparan sulfate chains (HS), which are coreceptors for APRIL and TACI, in tumors where APRIL is either overexpressed or is a prognostic factor. APRIL could induce survival or proliferation directly through HS proteoglycans. Taken together, these data suggest that APRIL is a potential prognostic factor for a large array of malignancies

  3. Matrix metalloproteinase-8 overexpression prevents proper tissue repair

    DEFF Research Database (Denmark)

    Danielsen, Patricia L; Holst, Anders V; Maltesen, Henrik R

    2011-01-01

    The collagenolytic matrix metalloproteinase-8 (MMP-8) is essential for normal tissue repair but is often overexpressed in wounds with disrupted healing. Our aim was to study the impact of a local excess of this neutrophil-derived proteinase on wound healing using recombinant adenovirus...

  4. Improvement of daptomycin yield by overexpression of the ...

    African Journals Online (AJOL)

    The effects of the accessory genes flanking the non-ribosomal peptide synthetase (NRPS) genes on daptomycin production were investigated by overexpression under the control of ermE* promoter via the integrative Escherichia coli–Streptomyces vector pIB139. The yield of daptomycin was promoted significantly when ...

  5. Brain phenotype of transgenic mice overexpressing cystathionine β-synthase.

    Directory of Open Access Journals (Sweden)

    Vinciane Régnier

    Full Text Available The cystathionine β-synthase (CBS gene, located on human chromosome 21q22.3, is a good candidate for playing a role in the Down Syndrome (DS cognitive profile: it is overexpressed in the brain of individuals with DS, and it encodes a key enzyme of sulfur-containing amino acid (SAA metabolism, a pathway important for several brain physiological processes.Here, we have studied the neural consequences of CBS overexpression in a transgenic mouse line (60.4P102D1 expressing the human CBS gene under the control of its endogenous regulatory regions. These mice displayed a ∼2-fold increase in total CBS proteins in different brain areas and a ∼1.3-fold increase in CBS activity in the cerebellum and the hippocampus. No major disturbance of SAA metabolism was observed, and the transgenic mice showed normal behavior in the rotarod and passive avoidance tests. However, we found that hippocampal synaptic plasticity is facilitated in the 60.4P102D1 line.We demonstrate that CBS overexpression has functional consequences on hippocampal neuronal networks. These results shed new light on the function of the CBS gene, and raise the interesting possibility that CBS overexpression might have an advantageous effect on some cognitive functions in DS.

  6. Laboratory and field studies of guayule modified to overexpress HMGR

    Science.gov (United States)

    We report the genetic modification of guayule to overexpress the isoprenoid pathway enzyme HMGR. The rubber content of two-month old in vitro transformed plantlets showed a 65% increase in rubber over the control for one line (HMGR6), and lower resin for another (HMGR2). In field evaluations HMGR6...

  7. Overexpression of CFH gene in pterygiumv patients | Bang | Tropical ...

    African Journals Online (AJOL)

    Overexpression of CFH gene in pterygiumv patients. Man-Seok Bang, Chang Rae Rho, Bong-Hui Kang, Kyong Jin Cho, Chung-Hun Oh. Abstract. Purpose: To investigate the expression of complement factors in pterygium tissues compared to normal conjunctival samples, using next-generation RNA sequencing. Methods: ...

  8. Brain phenotype of transgenic mice overexpressing cystathionine β-synthase.

    Science.gov (United States)

    Régnier, Vinciane; Billard, Jean-Marie; Gupta, Sapna; Potier, Brigitte; Woerner, Stéphanie; Paly, Evelyne; Ledru, Aurélie; David, Sabrina; Luilier, Sabrina; Bizot, Jean-Charles; Vacano, Guido; Kraus, Jan P; Patterson, David; Kruger, Warren D; Delabar, Jean M; London, Jaqueline

    2012-01-01

    The cystathionine β-synthase (CBS) gene, located on human chromosome 21q22.3, is a good candidate for playing a role in the Down Syndrome (DS) cognitive profile: it is overexpressed in the brain of individuals with DS, and it encodes a key enzyme of sulfur-containing amino acid (SAA) metabolism, a pathway important for several brain physiological processes. Here, we have studied the neural consequences of CBS overexpression in a transgenic mouse line (60.4P102D1) expressing the human CBS gene under the control of its endogenous regulatory regions. These mice displayed a ∼2-fold increase in total CBS proteins in different brain areas and a ∼1.3-fold increase in CBS activity in the cerebellum and the hippocampus. No major disturbance of SAA metabolism was observed, and the transgenic mice showed normal behavior in the rotarod and passive avoidance tests. However, we found that hippocampal synaptic plasticity is facilitated in the 60.4P102D1 line. We demonstrate that CBS overexpression has functional consequences on hippocampal neuronal networks. These results shed new light on the function of the CBS gene, and raise the interesting possibility that CBS overexpression might have an advantageous effect on some cognitive functions in DS.

  9. Constitutive overexpression of muscarinic receptors leads to vagal hyperreactivity.

    Directory of Open Access Journals (Sweden)

    Angelo Livolsi

    Full Text Available BACKGROUND: Alterations in muscarinic receptor expression and acetylcholinesterase (AchE activity have been observed in tissues from Sudden Infant Death Syndrome (SIDS. Vagal overactivity has been proposed as a possible cause of SIDS as well as of vasovagal syncopes. The aim of the present study was to seek whether muscarinic receptor overexpression may be the underlying mechanism of vagal hyperreactivity. Rabbits with marked vagal pauses following injection of phenylephrine were selected and crossed to obtain a vagal hyperreactive strain. The density of cardiac muscarinic receptors and acetylcholinesterase (AchE gene expression were assessed. Blood markers of the observed cardiac abnormalities were also sought. METHODOLOGY/PRINCIPAL FINDINGS: Cardiac muscarinic M(2 and M(3 receptors were overexpressed in hyperreactive rabbits compared to control animals (2.3-fold and 2.5-fold, respectively and the severity of the phenylephrine-induced bradycardia was correlated with their densities. A similar overexpression of M(2 receptors was observed in peripheral mononuclear white blood cells, suggesting that cardiac M(2 receptor expression can be inferred with high confidence from measurements in blood cells. Sequencing of the coding fragment of the M(2 receptor gene revealed a single nucleotide mutation in 83% of hyperreactive animals, possibly contributing for the transcript overexpression. Significant increases in AchE expression and activity were also assessed (AchE mRNA amplification ratio of 3.6 versus normal rabbits. This phenomenon might represent a compensatory consequence of muscarinic receptors overexpression. Alterations in M(2 receptor and AchE expression occurred between the 5th and the 7th week of age, a critical period also characterized by a higher mortality rate of hyperreactive rabbits (52% in H rabbits versus 13% in normal rabbits and preceeded the appearance of functional disorders. CONCLUSIONS/SIGNIFICANCE: The results suggest that

  10. Overexpression of the muscle-specific protein, melusin, protects from cardiac ischemia/reperfusion injury.

    Science.gov (United States)

    Penna, Claudia; Brancaccio, Mara; Tullio, Francesca; Rubinetto, Cristina; Perrelli, Maria-Giulia; Angotti, Carmelina; Pagliaro, Pasquale; Tarone, Guido

    2014-07-01

    Melusin is a muscle-specific protein which interacts with β1 integrin cytoplasmic domain and acts as chaperone protein. Its overexpression induces improved resistance to cardiac overload delaying left ventricle dilation and reducing the occurrence of heart failure. Here, we investigated possible protective effect of melusin overexpression against acute ischemia/reperfusion (I/R) injury with or without Postconditioning cardioprotective maneuvers. Melusin transgenic (Mel-TG) mice hearts were subjected to 30-min global ischemia followed by 60-min reperfusion. Interestingly, infarct size was reduced in Mel-TG mice hearts compared to wild-type (WT) hearts (40.3 ± 3.5 % Mel-TG vs. 59.5 ± 3.8 % WT hearts; n = 11 animals/group; P level of AKT, ERK1/2 and GSK3β phosphorylation, and displayed increased phospho-kinases level after I/R compared to WT mice. Post-ischemic Mel-TG hearts displayed also increased levels of the anti-apoptotic factor phospho-BAD. Importantly, pharmacological inhibition of PI3K/AKT (Wortmannin) and ERK1/2 (U0126) pathways abrogated the melusin protective effect. Notably, HSP90, a chaperone known to protect heart from I/R injury, showed high levels of expression in the heart of Mel-TG mice suggesting a possible collaboration of this molecule with AKT/ERK/GSK3β pathways in the melusin-induced protection. Postconditioning, known to activate AKT/ERK/GSK3β pathways, significantly reduced IS and LDH release in WT hearts, but had no additive protective effects in Mel-TG hearts. These findings implicate melusin as an enhancer of AKT and ERK pathways and as a novel player in cardioprotection from I/R injury.

  11. Overexpression of fatty acid amide hydrolase induces early flowering in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Neal D. Teaster

    2012-02-01

    Full Text Available N-Acylethanolamines (NAEs are bioactive lipids derived from the hydrolysis of the membrane phospholipid N-acylphosphatidylethanolamine (NAPE. In animal systems this reaction is part of the endocannabinoid signaling pathway, which regulates a variety of physiological processes. The signaling function of NAE is terminated by fatty acid amide hydrolase (FAAH, which hydrolyzes NAE to ethanolamine and free fatty acid. Our previous work in Arabidopsis thaliana showed that overexpression of AtFAAH (At5g64440 lowered endogenous levels of NAEs in seeds, consistent with its role in NAE signal termination. Reduced NAE levels were accompanied by an accelerated growth phenotype, increased sensitivity to abscisic acid (ABA, enhanced susceptibility to bacterial pathogens, and early flowering. Here we investigated the nature of the early flowering phenotype of AtFAAH overexpression. AtFAAH overexpressors flowered several days earlier than wild type and AtFAAH knockouts under both non-inductive short day (SD and inductive long day (LD conditions. Microarray analysis revealed that the FLOWERING LOCUS T (FT gene, which plays a major role in regulating flowering time, and one target MADS box transcription factor, SEPATALLA3 (SEP3, were elevated in AtFAAH overexpressors. Furthermore, AtFAAH overexpressors, with the early flowering phenotype had lower endogenous NAE levels in leaves compared to wild type prior to flowering. Exogenous application of NAE 12:0, which was reduced by up to 30% in AtFAAH overexpressors, delayed the onset of flowering in wild type plants. We conclude that the early flowering phenotype of AtFAAH overexpressors is, in part, explained by elevated FT gene expression resulting from the enhanced NAE hydrolase activity of AtFAAH, suggesting that NAE metabolism may participate in floral signaling pathways.

  12. UWB delay and multiply receiver

    Energy Technology Data Exchange (ETDEWEB)

    Dallum, Gregory E.; Pratt, Garth C.; Haugen, Peter C.; Romero, Carlos E.

    2013-09-10

    An ultra-wideband (UWB) delay and multiply receiver is formed of a receive antenna; a variable gain attenuator connected to the receive antenna; a signal splitter connected to the variable gain attenuator; a multiplier having one input connected to an undelayed signal from the signal splitter and another input connected to a delayed signal from the signal splitter, the delay between the splitter signals being equal to the spacing between pulses from a transmitter whose pulses are being received by the receive antenna; a peak detection circuit connected to the output of the multiplier and connected to the variable gain attenuator to control the variable gain attenuator to maintain a constant amplitude output from the multiplier; and a digital output circuit connected to the output of the multiplier.

  13. Chaos in the delay logistic equation with discontinuous delays

    International Nuclear Information System (INIS)

    Sen, Ayan; Mukherjee, Debasis

    2009-01-01

    This paper analyzes a delay logistic equation which models a feedback control problem. Interval map associated to the system is derived. By calculating Lyapunov exponent, we indicate stable orbit and chaotic phenomenon respectively. The results are verified through computer simulation. We identify the parameter which controls the dynamics.

  14. Postraumatic delayed loss of vision

    International Nuclear Information System (INIS)

    Partington, C.R.; Graves, V.B.; Ruetenacht, D.A.; Weinstein, J.M.; Strother, C.M.

    1989-01-01

    The imaging studies and clinical findings in 10 patients who suffered delayed vision loss beginning 1 day to 13 years after head trauma have been reviewed. Two different primary lesions could be identified: pseudoaneurysm of the internal carotid artery and carotid cavernous fistula. The pathologic changes associated with pseudoaneurysm included compression of the optic nerves and/or chiasm by arterial aneurysm and intracranial hematoma. Carotid cavernous fistula caused delayed vision loss by compression of the optic nerves and chiasm by saccular dilatation of the cavernous sinus and by abnormal orbital venous drainage with retinal venous stasis, retinal edema, and glaucoma

  15. Time delayed Ensemble Nudging Method

    Science.gov (United States)

    An, Zhe; Abarbanel, Henry

    Optimal nudging method based on time delayed embedding theory has shows potentials on analyzing and data assimilation in previous literatures. To extend the application and promote the practical implementation, new nudging assimilation method based on the time delayed embedding space is presented and the connection with other standard assimilation methods are studied. Results shows the incorporating information from the time series of data can reduce the sufficient observation needed to preserve the quality of numerical prediction, making it a potential alternative in the field of data assimilation of large geophysical models.

  16. 49 CFR 236.563 - Delay time.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Delay time. 236.563 Section 236.563 Transportation... Cab Signal Systems Rules and Instructions; Locomotives § 236.563 Delay time. Delay time of automatic... requirements of § 236.24 shall take into consideration the delay time. ...

  17. High eIF4E Overexpression in Node Negative Breast Cancer as Predictor for Recurrence

    National Research Council Canada - National Science Library

    Li, Benjamin

    2002-01-01

    .... EIF4E overexpression has been found in human malignancies (Li, 1997; Nathan, 1997). Furthermore, there appears to be an association of eIF4E overexpression and clinical outcomes (Li, 1998; Nathan, 1997; Li, 2001...

  18. Nmdmc overexpression extends Drosophila lifespan and reduces levels of mitochondrial reactive oxygen species

    International Nuclear Information System (INIS)

    Yu, Suyeun; Jang, Yeogil; Paik, Donggi; Lee, Eunil; Park, Joong-Jean

    2015-01-01

    NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase (NMDMC) is a bifunctional enzyme involved in folate-dependent metabolism and highly expressed in rapidly proliferating cells. However, Nmdmc physiological roles remain unveiled. We found that ubiquitous Nmdmc overexpression enhanced Drosophila lifespan and stress resistance. Interestingly, Nmdmc overexpression in the fat body was sufficient to increase lifespan and tolerance against oxidative stress. In addition, these conditions coincided with significant decreases in the levels of mitochondrial ROS and Hsp22 as well as with a significant increase in the copy number of mitochondrial DNA. These results suggest that Nmdmc overexpression should be beneficial for mitochondrial homeostasis and increasing lifespan. - Highlights: • Ubiquitous Nmdmc overexpression enhanced lifespan and stress tolerance. • Nmdmc overexpression in the fat body extended longevity. • Fat body-specific Nmdmc overexpression increased oxidative stress resistance. • Nmdmc overexpression decreased Hsp22 transcript levels and ROS. • Nmdmc overexpression increased mitochondrial DNA copy number.

  19. Nmdmc overexpression extends Drosophila lifespan and reduces levels of mitochondrial reactive oxygen species

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Suyeun [Department of Preventive Medicine, College of Medicine, Korea University, 73 Inchon-ro, Seongbuk-gu, Seoul 136-705 (Korea, Republic of); Jang, Yeogil; Paik, Donggi [Department of Physiology, College of Medicine, Korea University, 73 Inchon-ro, Seongbuk-gu, Seoul 136-705 (Korea, Republic of); Lee, Eunil, E-mail: eunil@korea.ac.kr [Department of Preventive Medicine, College of Medicine, Korea University, 73 Inchon-ro, Seongbuk-gu, Seoul 136-705 (Korea, Republic of); Park, Joong-Jean, E-mail: parkjj@korea.ac.kr [Department of Physiology, College of Medicine, Korea University, 73 Inchon-ro, Seongbuk-gu, Seoul 136-705 (Korea, Republic of)

    2015-10-02

    NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase (NMDMC) is a bifunctional enzyme involved in folate-dependent metabolism and highly expressed in rapidly proliferating cells. However, Nmdmc physiological roles remain unveiled. We found that ubiquitous Nmdmc overexpression enhanced Drosophila lifespan and stress resistance. Interestingly, Nmdmc overexpression in the fat body was sufficient to increase lifespan and tolerance against oxidative stress. In addition, these conditions coincided with significant decreases in the levels of mitochondrial ROS and Hsp22 as well as with a significant increase in the copy number of mitochondrial DNA. These results suggest that Nmdmc overexpression should be beneficial for mitochondrial homeostasis and increasing lifespan. - Highlights: • Ubiquitous Nmdmc overexpression enhanced lifespan and stress tolerance. • Nmdmc overexpression in the fat body extended longevity. • Fat body-specific Nmdmc overexpression increased oxidative stress resistance. • Nmdmc overexpression decreased Hsp22 transcript levels and ROS. • Nmdmc overexpression increased mitochondrial DNA copy number.

  20. Role of overexpressed CFA/I fimbriae in bacterial swimming.

    Science.gov (United States)

    Cao, Ling; Suo, Zhiyong; Lim, Timothy; Jun, Sangmu; Deliorman, Muhammedin; Riccardi, Carol; Kellerman, Laura; Avci, Recep; Yang, Xinghong

    2012-06-01

    Enterotoxigenic Escherichia coli CFA/I is a protective antigen and has been overexpressed in bacterial vectors, such as Salmonella Typhimurium H683, to generate vaccines. Effects that overexpressed CFA/I may engender on the bacterial host remain largely unexplored. To investigate, we constructed a high CFA/I expression strain, H683-pC2, and compared it to a low CFA/I expression strain, H683-pC, and to a non-CFA/I expression strain, H683-pY. The results showed that H683-pC2 was less able to migrate into semisolid agar (0.35%) than either H683-pC or H683-pY. Bacteria that migrated showed motility halo sizes of H683-pC2 CFA/I fimbriae on bacterial swimming motility.

  1. Overexpression of esterase D in kidney from trisomy 13 fetuses

    Energy Technology Data Exchange (ETDEWEB)

    Loughna, S.; Moore, G. (Institute of Obstetrics and Gynaecology, London (United Kingdom)); Gau, G.; Blunt, S. (Cytogenetics Lab., London (United Kingdom)); Nicolaides, K. (King' s College School of Medicine and Dentistry, London (United Kingdom))

    1993-10-01

    Human trisomy 13 (Patau syndrome) occurs in approximately 1 in 5,000 live births. It is compatible with life, but prolonged survival is rare. Anomalies often involve the urogenital, cardiac, craniofacial, and central nervous systems. It is possible that these abnormalities may be due to the overexpression of developmentally important genes on chromosome 13. The expression of esterase D (localized to chromosome 13q14.11) has been investigated in both muscle and kidney from trisomy 13 fetuses and has been compared with normal age- and sex-matched fetal tissues, by using northern analysis. More than a twofold increase in expression of esterase D was found in the kidney of two trisomy 13 fetuses, with normal levels in a third. Overexpression was not seen in the muscle tissues from these fetuses. 34 refs., 3 figs., 2 tabs.

  2. Transgenic overexpression of p23 induces spontaneous hydronephrosis in mice

    Science.gov (United States)

    Lee, Jaehoon; Kim, Hye Jin; Moon, Jung Ah; Sung, Young Hoon; Baek, In-Jeoung; Roh, Jae-il; Ha, Na Young; Kim, Seung-Yeon; Bahk, Young Yil; Lee, Jong Eun; Yoo, Tae Hyun; Lee, Han-Woong

    2011-01-01

    p23 is a cochaperone of heat shock protein 90 and also interacts functionally with numerous steroid receptors and kinases. However, the in vivo roles of p23 remain unclear. To explore its in vivo function, we generated the transgenic (TG) mice ubiquitously overexpressing p23. The p23 TG mice spontaneously developed kidney abnormalities closely resembling human hydronephrosis. Consistently, kidney functions deteriorate significantly in the p23 TG mice compared to their wild-type (WT) littermates. Furthermore, the expression of target genes for aryl hydrocarbon receptor (AhR), such as cytochrome P450, family 1, subfamily A, polypeptide 1 (Cyp1A1) and cytochrome P450, family 1, subfamily B, polypeptide 1 (Cyp1B1), were induced in the kidneys of the p23 TG mice. These results indicate that the overexpression of p23 contributes to the development of hydronephrosis through the upregulation of the AhR pathway in vivo. PMID:21323770

  3. Early-delayed radiation rhombencephalopathy

    International Nuclear Information System (INIS)

    Nightingale, S.; Dawes, P.J.D.K.; Cartlidge, N.E.F.; Newcastle upon Tyne Univ.

    1982-01-01

    A 37-year-old woman developed an early-delayed rhombencephalopathy 7 weeks after completing a course of radiotherapy to a glomus jugulare tumour. The clinical features, comprising nystagmus, skew strabismus, unilateral facial weakness, dysarthria and ataxia, are compared with four previously reported patients with this syndrome. (author)

  4. Another definition for time delay

    International Nuclear Information System (INIS)

    Narnhofer, H.

    1980-01-01

    Time delay is defined by geometrical considerations which work in classical as well as in quantum mechanics, and its connection with the S-matrix and the virial is proven for potentials with V(x vector) and x vector V(x vector) vanishing as rsup(-1-epsilon) for r -> infinity. (Author)

  5. Weather delay costs to trucking.

    Science.gov (United States)

    2012-11-01

    Estimates of the nations freight sector of transportation range to upwards of $600 billion of total gross domestic product with 70 percent of total value and 60 percent of total weight moving by truck. Weather-related delays can add significantly ...

  6. Diagnostic Delay in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Mølbaek, Karen; Hørslev-Petersen, Kim; Primdahl, Jette

    2016-01-01

    BACKGROUND: To prevent joint damage among patients with rheumatoid arthritis (RA), there is a need to minimize delays from the onset of symptoms until the initiation of appropriate therapy. The present study explored the factors that have an impact on the time it takes for Danish patients with RA...

  7. Design flaw could delay collider

    CERN Multimedia

    Cho, Adrian

    2007-01-01

    "A magnet for the Large Hadron Collider (LHC) failed during a key test at the European particle physics laboratory CERN last week. Physicists and engineers will have to repair the damaged magnet and retrofit others to correct the underlynig design flaw, which could delay the start-up of the mammouth subterranean machine." (1,5 page)

  8. Concurrent Delay in Construction Disputes

    DEFF Research Database (Denmark)

    Cavaleri, Sylvie Cécile

    the delay is contractually defined as a contractor's risk, the contractor is liable to pay liquidated damages to the employer; if it is not, the contractor can under certain circumstances claim an extension of time and in some cases also economic compensation from the employer. The situation where a given...

  9. Deconstructing delayed posttraumatic stress disorder

    NARCIS (Netherlands)

    Smid, G

    2011-01-01

    According to the Diagnostic and Statistical Manual of Mental Disorders, delayed posttraumatic stress disorder (PTSD) must be diagnosed in individuals fulfilling criteria for PTSD if the onset of symptoms is at least six months after the trauma. The purpose of this thesis was to establish the

  10. Livermore blasted for project delay

    CERN Multimedia

    1999-01-01

    In a 12 page report issued last week, a review committee set up by the University of California has concluded that mismanagement and poor planning are to blame for significant cost overruns and delays in the construction of NIF, the worlds largest laser (1 page).

  11. Providing delay guarantees in Bluetooth

    NARCIS (Netherlands)

    Ait Yaiz, R.; Heijenk, Geert; Titsworth, F.

    2003-01-01

    Bluetooth polling, also referred to as Bluetooth MAC scheduling or intra-piconet scheduling, is the mechanism that schedules the traffic between the participants in a Bluetooth network. Hence, this mechanism is highly determining with respect to the delay packets experience in a Bluetooth network.

  12. Overexpression of the riboflavin biosynthetic pathway in Pichia pastoris

    Directory of Open Access Journals (Sweden)

    Mattanovich Diethard

    2008-07-01

    Full Text Available Abstract Background High cell density cultures of Pichia pastoris grown on methanol tend to develop yellow colored supernatants, attributed to the release of free flavins. The potential of P. pastoris for flavin overproduction is therefore given, but not pronounced when the yeast is grown on glucose. The aim of this study is to characterize the relative regulatory impact of each riboflavin synthesis gene. Deeper insight into pathway control and the potential of deregulation is established by overexpression of the single genes as well as a combined deregulation of up to all six riboflavin synthesis genes. Results Overexpression of the first gene of the riboflavin biosynthetic pathway (RIB1 is already sufficient to obtain yellow colonies and the accumulation of riboflavin in the supernatant of shake flask cultures growing on glucose. Sequential deregulation of all the genes, by exchange of their native promoter with the strong and constitutive glyceraldehyde-3-phosphate dehydrogenase promoter (PGAP increases the riboflavin accumulation significantly. Conclusion The regulation of the pathway is distributed over more than one gene. High cell density cultivations of a P. pastoris strain overexpressing all six RIB genes allow the accumulation of 175 mg/L riboflavin in the supernatant. The basis for rational engineering of riboflavin production in P. pastoris has thus been established.

  13. Role of overexpressed CFA/I fimbriae in bacterial swimming

    International Nuclear Information System (INIS)

    Cao, Ling; Lim, Timothy; Jun, SangMu; Riccardi, Carol; Yang, Xinghong; Suo, Zhiyong; Deliorman, Muhammedin; Kellerman, Laura; Avci, Recep

    2012-01-01

    Enterotoxigenic Escherichia coli CFA/I is a protective antigen and has been overexpressed in bacterial vectors, such as Salmonella Typhimurium H683, to generate vaccines. Effects that overexpressed CFA/I may engender on the bacterial host remain largely unexplored. To investigate, we constructed a high CFA/I expression strain, H683-pC2, and compared it to a low CFA/I expression strain, H683-pC, and to a non-CFA/I expression strain, H683-pY. The results showed that H683-pC2 was less able to migrate into semisolid agar (0.35%) than either H683-pC or H683-pY. Bacteria that migrated showed motility halo sizes of H683-pC2 < H683-pC < H683-pY. In the liquid culture media, H683-pC2 cells precipitated to the bottom of the tube, while those of H683-pY did not. In situ imaging revealed that H683-pC2 bacilli tended to auto-agglutinate within the semisolid agar, while H683-pY bacilli did not. When the cfaBE fimbrial fiber encoding genes were deleted from pC2, the new plasmid, pC2(-), significantly recovered bacterial swimming capability. Our study highlights the negative impact of overexpressed CFA/I fimbriae on bacterial swimming motility. (paper)

  14. Overexpression of NPR1 in Brassica juncea Confers Broad Spectrum Resistance to Fungal Pathogens

    Directory of Open Access Journals (Sweden)

    Sajad Ali

    2017-10-01

    Full Text Available Brassica juncea (Indian mustard is a commercially important oil seed crop, which is highly affected by many biotic stresses. Among them, Alternaria leaf blight and powdery mildew are the most devastating diseases leading to huge yield losses in B. juncea around the world. In this regard, genetic engineering is a promising tool that may possibly allow us to enhance the B. juncea disease resistance against these pathogens. NPR1 (non-expressor of pathogen-related gene 1 is a bonafide receptor of salicylic acid (SA which modulates multiple immune responses in plants especially activation of induced and systemic acquired resistance (SAR. Here, we report the isolation and characterization of new NPR1 homolog (BjNPR1 from B. juncea. The phylogenetic tree constructed based on the deduced sequence of BjNPR1 with homologs from other species revealed that BjNPR1 grouped together with other known NPR1 proteins of Cruciferae family, and was nearest to B. napus. Furthermore, expression analysis showed that BjNPR1 was upregulated after SA treatment and fungal infection but not by jasmonic acid or abscisic acid. To understand the defensive role of this gene, we generated B. juncea transgenic lines overexpressing BjNPR1, and further confirmed by PCR and Southern blotting. The transgenic lines showed no phenotypic abnormalities, and constitutive expression of BjNPR1 activates defense signaling pathways by priming the expression of antifungal PR genes. Moreover, BjNPR1 transgenic lines showed enhanced resistance to Alternaria brassicae and Erysiphe cruciferarum as there was delay in symptoms and reduced disease severity than non-transgenic plants. In addition, the rate of disease spreading to uninfected or distal parts was also delayed in transgenic plants thus suggesting the activation of SAR. Altogether, the present study suggests that BjNPR1 is involved in broad spectrum of disease resistance against fungal pathogens.

  15. Analysis of a first-order delay differential-delay equation containing two delays

    Science.gov (United States)

    Marriott, C.; Vallée, R.; Delisle, C.

    1989-09-01

    An experimental and numerical analysis of the behavior of a two-delay differential equation is presented. It is shown that much of the system's behavior can be related to the stability behavior of the underlying linearized modes. A new phenomenon, mode crossing, is explored.

  16. Modulation of ethylene responses by OsRTH1 overexpression reveals the biological significance of ethylene in rice seedling growth and development

    Science.gov (United States)

    Zhang, Wei; Zhou, Xin; Wen, Chi-Kuang

    2012-01-01

    Overexpression of Arabidopsis Reversion-To-ethylene Sensitivity1 (RTE1) results in whole-plant ethylene insensitivity dependent on the ethylene receptor gene Ethylene Response1 (ETR1). However, overexpression of the tomato RTE1 homologue Green Ripe (GR) delays fruit ripening but does not confer whole-plant ethylene insensitivity. It was decided to investigate whether aspects of ethylene-induced growth and development of the monocotyledonous model plant rice could be modulated by rice RTE1 homologues (OsRTH genes). Results from a cross-species complementation test in Arabidopsis showed that OsRTH1 overexpression complemented the rte1-2 loss-of-function mutation and conferred whole-plant ethylene insensitivity in an ETR1-dependent manner. In contrast, OsRTH2 and OsRTH3 overexpression did not complement rte1-2 or confer ethylene insensitivity. In rice, OsRTH1 overexpression substantially prevented ethylene-induced alterations in growth and development, including leaf senescence, seedling leaf elongation and development, coleoptile elongation or curvature, and adventitious root development. Results of subcellular localizations of OsRTHs, each fused with the green fluorescent protein, in onion epidermal cells suggested that the three OsRTHs were predominantly localized to the Golgi. OsRTH1 may be an RTE1 orthologue of rice and modulate rice ethylene responses. The possible roles of auxins and gibberellins in the ethylene-induced alterations in growth were evaluated and the biological significance of ethylene in the early stage of rice seedling growth is discussed. PMID:22451723

  17. Overexpressed CacyBP/SIP leads to the suppression of growth in renal cell carcinoma

    International Nuclear Information System (INIS)

    Sun, Shiren; Ning, Xiaoxuan; Liu, Jie; Liu, Lili; Chen, Yu; Han, Shuang; Zhang, Yanqi; Liang, Jie; Wu, Kaichun; Fan, Daiming

    2007-01-01

    Calcyclin-binding protein/Siah-1-interacting protein (CacyBP/SIP), a target protein of S100, has been identified as a component of a novel ubiquitinylation complex leading to β-catenin degradation, which was found to be related to the malignant phenotypes of gastric cancer. However, the roles of CacyBP/SIP in renal cell carcinoma still remain unclear. In the present study, we had analyzed the expression of the CacyBP/SIP protein in human renal cancer cells and clinical tissue samples. The possible roles of CacyBP/SIP in regulating the malignant phenotype of renal cancer cells were also investigated. The results demonstrated that the expression of CacyBP/SIP was markedly down-regulated in renal cell carcinoma tissues and cell lines. Ectopic overexpression of CacyBP/SIP in A498 cells inhibited the proliferation of this cell and delayed cell cycle progression significantly, which might be related to the down-regulation of Cyclin D1 through reducing β-catenin protein. CacyBP/SIP also suppressed colony formation in soft agar and its tumorigenicity in nude mice. Taken together, our work showed that CacyBP/SIP, as a novel down-regulated gene in renal cell carcinoma, suppressed proliferation and tumorigenesis of renal cancer cells

  18. Altered Fruit and Seed Development of Transgenic Rapeseed (Brassica napus Over-Expressing MicroRNA394.

    Directory of Open Access Journals (Sweden)

    Jian Bo Song

    Full Text Available Fruit and seed development in plants is a complex biological process mainly involved in input and biosynthesis of many storage compounds such as proteins and oils. Although the basic biochemical pathways for production of the storage metabolites in plants are well characterized, their regulatory mechanisms are not fully understood. In this study, we functionally identified rapeseed (Brassica napus miR394 with its target gene Brassica napus leaf curling responsiveness (BnLCR to dissect a role of miR394 during the fruit and seed development. Transgenic rapeseed plants over-expressing miR394 under the control of the cauliflower mosaic virus 35S promoter were generated. miR394 over-expression plants exhibited a delayed flowering time and enlarged size of plants, leaf blade, pods and seed body, but developed seeds with higher contents of protein and glucosinolates (GLS and lower levels of oil accumulation as compared to wild-type. Over-expression of miR394 altered the fatty acid (FA composition by increasing several FA species such as C16:0 and C18:0 and unsaturated species of C20:1 and C22:1 but lowering C18:3. This change was accompanied by induction of genes coding for transcription factors of FA synthesis including leafy cotyledon1 (BnLEC1, BnLEC2, and FUSCA3 (FUS3. Because the phytohormone auxin plays a crucial role in fruit development and seed patterning, the DR5-GUS reporter was used for monitoring the auxin response in Arabidopsis siliques and demonstrated that the DR5 gene was strongly expressed. These results suggest that BnmiR394 is involved in rapeseed fruit and seed development.

  19. Minimum Delay Moving Object Detection

    KAUST Repository

    Lao, Dong

    2017-11-09

    We present a general framework and method for detection of an object in a video based on apparent motion. The object moves relative to background motion at some unknown time in the video, and the goal is to detect and segment the object as soon it moves in an online manner. Due to unreliability of motion between frames, more than two frames are needed to reliably detect the object. Our method is designed to detect the object(s) with minimum delay, i.e., frames after the object moves, constraining the false alarms. Experiments on a new extensive dataset for moving object detection show that our method achieves less delay for all false alarm constraints than existing state-of-the-art.

  20. Depressive illness delayed Hamlet's revenge.

    Science.gov (United States)

    Shaw, A B; Pickering, Neil

    2002-12-01

    If Hamlet had not delayed his revenge there would have been no play. Many explanations of the delay have been offered in the last four centuries. None is convincing. The interpretation which best fits the evidence best is that Hamlet was suffering from an acute depressive illness, with some obsessional features. He could not make a firm resolve to act. In Shakespeare's time there was no concept of acute depressive illness, although melancholy was well known. Melancholy, however, would have been seen as a character defect. In the tragic model the hero brings himself and others to ruin because of a character defect. Thus, at the time, the play conformed to the tragic model. With today's knowledge, it does not. This analysis adds to, but does not replace, other insights into the play.

  1. Air congestion delay: a review

    Directory of Open Access Journals (Sweden)

    Daniel Alberto Pamplona

    2016-04-01

    Full Text Available This article is a literature review of the air congestion delay and its costs. Air congestion is a worldwide problem. Its existence brings costs for airlines and discomfort for passengers. With the increasing demand for air transport, the study of air congestion has attracted the attention of many researchers around the world. The cause for the delays is erroneously attributed only to the lack of infrastructure investments. The literature review shows that other factors such as population growth, increasing standards of living, lack of operational planning and environmental issues exercise decisive influence. Several studies have been conducted in order to analyze and propose solutions to this problem that affects society as a whole.

  2. Minimum Delay Moving Object Detection

    KAUST Repository

    Lao, Dong

    2017-01-08

    We present a general framework and method for detection of an object in a video based on apparent motion. The object moves relative to background motion at some unknown time in the video, and the goal is to detect and segment the object as soon it moves in an online manner. Due to unreliability of motion between frames, more than two frames are needed to reliably detect the object. Our method is designed to detect the object(s) with minimum delay, i.e., frames after the object moves, constraining the false alarms. Experiments on a new extensive dataset for moving object detection show that our method achieves less delay for all false alarm constraints than existing state-of-the-art.

  3. Minimum Delay Moving Object Detection

    KAUST Repository

    Lao, Dong; Sundaramoorthi, Ganesh

    2017-01-01

    We present a general framework and method for detection of an object in a video based on apparent motion. The object moves relative to background motion at some unknown time in the video, and the goal is to detect and segment the object as soon it moves in an online manner. Due to unreliability of motion between frames, more than two frames are needed to reliably detect the object. Our method is designed to detect the object(s) with minimum delay, i.e., frames after the object moves, constraining the false alarms. Experiments on a new extensive dataset for moving object detection show that our method achieves less delay for all false alarm constraints than existing state-of-the-art.

  4. Overexpression of Indian hedgehog partially rescues short stature homeobox 2-overexpression-associated congenital dysplasia of the temporomandibular joint in mice

    Science.gov (United States)

    LI, XIHAI; LIANG, WENNA; YE, HONGZHI; WENG, XIAPING; LIU, FAYUAN; LIN, PINGDONG; LIU, XIANXIANG

    2015-01-01

    The role of short stature homeobox 2 (shox2) in the development and homeostasis of the temporomandibular joint (TMJ) has been well documented. Shox2 is known to be expressed in the progenitor cells and perichondrium of the developing condyle. A previous study by our group reported that overexpression of shox2 leads to congenital dysplasia of the TMJ via downregulation of the Indian hedgehog (Ihh) signaling pathway, which is essential for embryonic disc primordium formation and mandibular condylar growth. To determine whether overexpression of Ihh may rescue the overexpression of shox2 leading to congenital dysplasia of the TMJ, a mouse model in which Ihh and shox2 were overexpressed (Wnt1-Cre; pMes-stop shox2; pMes-stop Ihh mice) was utilized to assess the consequences of this overexpression on TMJ development during post-natal life. The results showed that the developmental process and expression levels of runt-related transcription factor 2 and sex determining region Y-box 9 in the TMJ of the Wnt1-Cre; pMes-stop shox2; pMes-stop Ihh mice were similar to those in wild-type mice. Overexpression of Ihh rescued shox2 overexpression-associated reduction of extracellular matrix components. However, overexpression of Ihh did not inhibit the shox2 overexpression-associated increase of matrix metalloproteinases (MMPs) MMP9, MMP13 and apoptosis in the TMJ. These combinatory cellular and molecular defects appeared to account for the observed congenital dysplasia of TMJ, suggesting that overexpression of Ihh partially rescued shox2 overexpression-associated congenital dysplasia of the TMJ in mice. PMID:26096903

  5. Teriparatide Induced Delayed Persistent Hypercalcemia

    Directory of Open Access Journals (Sweden)

    Nirosshan Thiruchelvam

    2014-01-01

    Full Text Available Teriparatide, a recombinant PTH, is an anabolic treatment for osteoporosis that increases bone density. Transient hypercalcemia is a reported side effect of teriparatide that is seen few hours following administration of teriparatide and resolves usually within 16 hours of drug administration. Persistent hypercalcemia, although not observed in clinical trials, is rarely reported. The current case describes a rare complication of teriparatide induced delayed persistent hypercalcemia.

  6. Assembly delay line pulse generators

    CERN Multimedia

    CERN PhotoLab

    1971-01-01

    Assembly of six of the ten delay line pulse generators that will power the ten kicker magnet modules. One modulator part contains two pulse generators. Capacitors, inductances, and voltage dividers are in the oil tank on the left. Triggered high-pressure spark gap switches are on the platforms on the right. High voltage pulse cables to the kicker magnet emerge under the spark gaps. In the centre background are the assembled master gaps.

  7. Ectopic expression of Capsicum-specific cell wall protein Capsicum annuum senescence-delaying 1 (CaSD1) delays senescence and induces trichome formation in Nicotiana benthamiana.

    Science.gov (United States)

    Seo, Eunyoung; Yeom, Seon-In; Jo, Sunghwan; Jeong, Heejin; Kang, Byoung-Cheorl; Choi, Doil

    2012-04-01

    Secreted proteins are known to have multiple roles in plant development, metabolism, and stress response. In a previous study to understand the roles of secreted proteins, Capsicum annuum secreted proteins (CaS) were isolated by yeast secretion trap. Among the secreted proteins, we further characterized Capsicum annuum senescence-delaying 1 (CaSD1), a gene encoding a novel secreted protein that is present only in the genus Capsicum. The deduced CaSD1 contains multiple repeats of the amino acid sequence KPPIHNHKPTDYDRS. Interestingly, the number of repeats varied among cultivars and species in the Capsicum genus. CaSD1 is constitutively expressed in roots, and Agrobacterium-mediated transient overexpression of CaSD1 in Nicotiana benthamiana leaves resulted in delayed senescence with a dramatically increased number of trichomes and enlarged epidermal cells. Furthermore, senescence- and cell division-related genes were differentially regulated by CaSD1-overexpressing plants. These observations imply that the pepper-specific cell wall protein CaSD1 plays roles in plant growth and development by regulating cell division and differentiation.

  8. Minimum Delay Moving Object Detection

    KAUST Repository

    Lao, Dong

    2017-05-14

    This thesis presents a general framework and method for detection of an object in a video based on apparent motion. The object moves, at some unknown time, differently than the “background” motion, which can be induced from camera motion. The goal of proposed method is to detect and segment the object as soon it moves in an online manner. Since motion estimation can be unreliable between frames, more than two frames are needed to reliably detect the object. Observing more frames before declaring a detection may lead to a more accurate detection and segmentation, since more motion may be observed leading to a stronger motion cue. However, this leads to greater delay. The proposed method is designed to detect the object(s) with minimum delay, i.e., frames after the object moves, constraining the false alarms, defined as declarations of detection before the object moves or incorrect or inaccurate segmentation at the detection time. Experiments on a new extensive dataset for moving object detection show that our method achieves less delay for all false alarm constraints than existing state-of-the-art.

  9. Development of delayed radiation necrosis

    International Nuclear Information System (INIS)

    Ohara, ShigFeki; Takagi, Terumasa; Shibata, Taichiro; Nagai, Hajime.

    1983-01-01

    The authors discussed the developing process of delayed radiation necrosis of the brain from the case of a 42-year-old female who developed intracranial hypertension and left hemiparesis 5 and a half years after radiotherapy for pituitary adenoma. The initial sign of radiation necrosis was from a CT scan taken 3 and a half years after radiotherapy showing an irregular low density lesion in the right temporal lobe. CT scan 2 years later demonstrated displacement of the midline structures to the left and a larger low density lesion with partially high density in the right MCA territory that was enhanced with intravenous contrast medium. Recovery after a right temporal lobectomy and administration of steroid hormone were uneventful. Eight months later there were no signs of raised intracranial pressure nor of neurological deficits. Tissues obtained from the right temporal lobe at lobectomy revealed the characteristic changes of delayed radiation necrosis; a mixture of fresh, recent, and old vascular lesions in the same specimen. From these findings, it was speculated that delayed radiation necrosis might initially occur within several years after radiotherapy and might gradually take a progressive and extended course, even in cases whose clinical symptoms develop much later. (author)

  10. Differences in radiosensitivity between three HER2 overexpressing cell lines

    International Nuclear Information System (INIS)

    Steffen, Ann-Charlott; Tolmachev, Vladimir; Stenerloew, Bo; Goestring, Lovisa; Palm, Stig; Carlsson, Joergen

    2008-01-01

    HER2 is a potential target for radionuclide therapy, especially when HER2 overexpressing breast cancer cells are resistant to Herceptin registered treatment. Therefore, it is of interest to analyse whether HER2 overexpressing tumour cells have different inherent radiosensitivity. The radiosensitivity of three often used HER2 overexpressing cell lines, SKOV-3, SKBR-3 and BT-474, was analysed. The cells were exposed to conventional photon irradiation, low linear energy transfer (LET), to characterise their inherent radiosensitivity. The analysis was made with clonogenic survival and growth extrapolation assays. The cells were also exposed to alpha particles, high LET, from 211 At decays using the HER2-binding affibody molecule 211 At-(Z HER2:4 ) 2 as targeting agent. Assays for studies of internalisation of the affibody molecule were applied. SKOV-3 cells were most radioresistant, SKBR-3 cells were intermediate and BT-474 cells were most sensitive as measured with the clonogenic and growth extrapolation assays after photon irradiation. The HER2 dependent cellular uptake of 211 At was qualitatively similar for all three cell lines. However, the sensitivity to the alpha particles from 211 At differed; SKOV-3 was most resistant, SKBR-3 intermediate and BT-474 most sensitive. These differences were unexpected because it is assumed that all types of cells should have similar sensitivity to high-LET radiation. The sensitivity to alpha particle exposure correlated with internalisation of the affibody molecule and with size of the cell nucleus. There can be differences in radiosensitivity, which, if they also exist between patient breast cancer cells, are important to consider for both conventional radiotherapy and for HER2-targeted radionuclide therapy. (orig.)

  11. Synchronization in networks with heterogeneous coupling delays

    Science.gov (United States)

    Otto, Andreas; Radons, Günter; Bachrathy, Dániel; Orosz, Gábor

    2018-01-01

    Synchronization in networks of identical oscillators with heterogeneous coupling delays is studied. A decomposition of the network dynamics is obtained by block diagonalizing a newly introduced adjacency lag operator which contains the topology of the network as well as the corresponding coupling delays. This generalizes the master stability function approach, which was developed for homogenous delays. As a result the network dynamics can be analyzed by delay differential equations with distributed delay, where different delay distributions emerge for different network modes. Frequency domain methods are used for the stability analysis of synchronized equilibria and synchronized periodic orbits. As an example, the synchronization behavior in a system of delay-coupled Hodgkin-Huxley neurons is investigated. It is shown that the parameter regions where synchronized periodic spiking is unstable expand when increasing the delay heterogeneity.

  12. CREB Overexpression Ameliorates Age-related Behavioral and Biophysical Deficits

    Science.gov (United States)

    Yu, Xiao-Wen

    Age-related cognitive deficits are observed in both humans and animals. Yet, the molecular mechanisms underlying these deficits are not yet fully elucidated. In aged animals, a decrease in intrinsic excitability of pyramidal neurons from the CA1 sub-region of hippocampus is believed to contribute to age-related cognitive impairments, but the molecular mechanism(s) that modulate both these factors has yet to be identified. Increasing activity of the transcription factor cAMP response element-binding protein (CREB) in young adult rodents has been shown to facilitate cognition, and increase intrinsic excitability of their neurons. However, how CREB changes with age, and how that impacts cognition in aged animals, is not clear. Therefore, we first systematically characterized age- and training-related changes in CREB levels in dorsal hippocampus. At a remote time point after undergoing behavioral training, levels of total CREB and activated CREB (phosphorylated at S133, pCREB) were measured in both young and aged rats. We found that pCREB, but not total CREB was significantly reduced in dorsal CA1 of aged rats. Importantly, levels of pCREB were found to be positively correlated with short-term spatial memory in both young and aged rats i.e. higher pCREB in dorsal CA1 was associated with better spatial memory. These findings indicate that an age-related deficit in CREB activity may contribute to the development of age-related cognitive deficits. However, it was still unclear if increasing CREB activity would be sufficient to ameliorate age-related cognitive, and biophysical deficits. To address this question, we virally overexpressed CREB in CA1, where we found the age-related deficit. Young and aged rats received control or CREB virus, and underwent water maze training. While control aged animals exhibited deficits in long-term spatial memory, aged animals with CREB overexpression performed at levels comparable to young animals. Concurrently, aged neurons

  13. MMP20 Overexpression Disrupts Molar Ameloblast Polarity and Migration.

    Science.gov (United States)

    Shin, M; Chavez, M B; Ikeda, A; Foster, B L; Bartlett, J D

    2018-02-01

    Ameloblasts responsible for enamel formation express matrix metalloproteinase 20 (MMP20), an enzyme that cleaves enamel matrix proteins, including amelogenin (AMELX) and ameloblastin (AMBN). Previously, we showed that continuously erupting incisors from transgenic mice overexpressing active MMP20 had a massive cell infiltrate present within their enamel space, leading to enamel mineralization defects. However, effects of MMP20 overexpression on mouse molars were not analyzed, although these teeth more accurately represent human odontogenesis. Therefore, MMP20-overexpressing mice ( Mmp20 +/+ Tg + ) were assessed by multiscale analyses, combining several approaches from high-resolution micro-computed tomography to enamel organ immunoblots. During the secretory stage at postnatal day 6 (P6), Mmp20 +/+ Tg + mice had a discontinuous ameloblast layer and, unlike incisors, molar P12 maturation stage ameloblasts abnormally migrated away from the enamel layer into the stratum intermedium/stellate reticulum. TOPflash assays performed in vitro demonstrated that MMP20 expression promoted β-catenin nuclear localization and that MMP20 expression promoted invasion through Matrigel-coated filters. However, for both assays, significant differences were eliminated in the presence of the β-catenin inhibitor ICG-001. This suggests that MMP20 activity promotes cell migration via the Wnt pathway. In vivo, the unique molar migration of amelogenin-expressing ameloblasts was associated with abnormal deposition of ectopic calcified nodules surrounding the adherent enamel layer. Enamel content was assessed just prior to eruption at P15. Compared to wild-type, Mmp20 +/+ Tg + molars exhibited significant reductions in enamel thickness (70%), volume (60%), and mineral density (40%), and MMP20 overexpression resulted in premature cleavage of AMBN, which likely contributed to the severe defects in enamel mineralization. In addition, Mmp20 +/+ Tg + mouse molar enamel organs had increased levels

  14. Upregulation of triglyceride synthesis in skeletal muscle overexpressing DGAT1

    OpenAIRE

    Yang, Feifei; Wei, Zhuying; Ding, Xiangbin; Liu, Xinfeng; Ge, Xiuguo; Song, Guimin; Li, Guangpeng; Guo, Hong

    2013-01-01

    The gene encoding diacylglycerol acyltransferase (DGAT1) is a functional and positional candidate gene for milk and intramuscular fat content. A bovine DGAT1 overexpression vector was constructed containing mouse MCK promoter and bovine DGAT1 cDNA. MCK-DGAT1 transgene in FVB mice was researched in present study. The transgene DGAT1 had a high level of expression in contrast to the endogenous DGAT1 in posterior tibial muscle of the transgenic mice, but a low expression level in the cardiac mus...

  15. Targeting GPR110 in HER2-Overexpressing Breast Cancers

    Science.gov (United States)

    2015-10-01

    34assay"using"the"transwell" inserts"with" (A)"or"without" (B)"matrigel" for"SKBR3" cells "transfected"with"nonAtarge1ng"( NT1 )"orŗ"independent"GPR110"siRNAs...HER2 drug resistant cells and in tumorigenic population using a broad panel of cell line models. We have successfully generated inducible lentiviral...plasmids with GPR110 cDNA and cell lines that inducibly overexpress GPR110. Generation of cell lines with lentiviral plasmids containing GPR110

  16. BRCA1-IRIS Overexpression Promotes Formation of Aggressive Breast Cancers

    Science.gov (United States)

    Shimizu, Yoshiko; Luk, Hugh; Horio, David; Miron, Penelope; Griswold, Michael; Iglehart, Dirk; Hernandez, Brenda; Killeen, Jeffrey; ElShamy, Wael M.

    2012-01-01

    Introduction Women with HER2+ or triple negative/basal-like (TN/BL) breast cancers succumb to their cancer rapidly due, in part to acquired Herceptin resistance and lack of TN/BL-targeted therapies. BRCA1-IRIS is a recently discovered, 1399 residue, BRCA1 locus alternative product, which while sharing 1365 residues with the full-length product of this tumor suppressor gene, BRCA1/p220, it has oncoprotein-like properties. Here, we examine whether BRCA1-IRIS is a valuable treatment target for HER2+ and/or TN/BL tumors. Methodology/Principal Findings Immunohistochemical staining of large cohort of human breast tumor samples using new monoclonal anti-BRCA1-IRIS antibody, followed by correlation of BRCA1-IRIS expression with that of AKT1, AKT2, p-AKT, survivin and BRCA1/p220, tumor status and age at diagnosis. Generation of subcutaneous tumors in SCID mice using human mammary epithelial (HME) cells overexpressing TERT/LT/BRCA1-IRIS, followed by comparing AKT, survivin, and BRCA1/p220 expression, tumor status and aggressiveness in these tumors to that in tumors developed using TERT/LT/RasV12-overexpressing HME cells. Induction of primary and invasive rat mammary tumors using the carcinogen N-methyl-N-nitrosourea (NMU), followed by analysis of rat BRCA1-IRIS and ERα mRNA levels in these tumors. High BRCA1-IRIS expression was detected in the majority of human breast tumors analyzed, which was positively correlated with that of AKT1-, AKT2-, p-AKT-, survivin, but negatively with BRCA1/p220 expression. BRCA1-IRIS-positivity induced high-grade, early onset and metastatic HER2+ or TN/BL tumors. TERT/LT/BRCA1-IRIS overexpressing HME cells formed invasive subcutaneous tumors that express high AKT1, AKT2, p-AKT and vimentin, but no CK19, p63 or BRCA1/p220. NMU-induced primary and invasive rat breast cancers expressed high levels of rat BRCA1-IRIS mRNA but low levels of rat ERα mRNA. Conclusion/Significance BRCA1-IRIS overexpression triggers aggressive breast tumor formation

  17. Hepatic steatosis in transgenic mice overexpressing human histone deacetylase 1

    International Nuclear Information System (INIS)

    Wang, Ai-Guo; Seo, Sang-Beom; Moon, Hyung-Bae; Shin, Hye-Jun; Kim, Dong Hoon; Kim, Jin-Man; Lee, Tae-Hoon; Kwon, Ho Jeong; Yu, Dae-Yeul; Lee, Dong-Seok

    2005-01-01

    It is generally thought that histone deacetylases (HDACs) play important roles in the transcriptional regulation of genes. However, little information is available concerning the specific functions of individual HDACs in disease states. In this study, two transgenic mice lines were established which harbored the human HDAC1 gene. Overexpressed HDAC1 was detected in the nuclei of transgenic liver cells, and HDAC1 enzymatic activity was significantly higher in the transgenic mice than in control littermates. The HDAC1 transgenic mice exhibited a high incidence of hepatic steatosis and nuclear pleomorphism. Molecular studies showed that HDAC1 may contribute to nuclear pleomorphism through the p53/p21 signaling pathway

  18. Synchronization analysis of coloured delayed networks under ...

    Indian Academy of Sciences (India)

    This paper investigates synchronization of coloured delayed networks under decentralized pinning intermittent control. To begin with, the time delays are taken into account in the coloured networks. In addition, we propose a decentralized pinning intermittent control for coloured delayed networks, which is different from that ...

  19. Overexpression of Indian hedgehog partially rescues short stature homeobox 2-overexpression-associated congenital dysplasia of the temporomandibular joint in mice.

    Science.gov (United States)

    Li, Xihai; Liang, Wenna; Ye, Hongzhi; Weng, Xiaping; Liu, Fayuan; Lin, Pingdong; Liu, Xianxiang

    2015-09-01

    The role of short stature homeobox 2 (shox2) in the development and homeostasis of the temporomandibular joint (TMJ) has been well documented. Shox2 is known to be expressed in the progenitor cells and perichondrium of the developing condyle. A previous study by our group reported that overexpression of shox2 leads to congenital dysplasia of the TMJ via downregulation of the Indian hedgehog (Ihh) signaling pathway, which is essential for embryonic disc primordium formation and mandibular condylar growth. To determine whether overexpression of Ihh may rescue the overexpression of shox2 leading to congenital dysplasia of the TMJ, a mouse model in which Ihh and shox2 were overexpressed (Wnt1-Cre; pMes-stop shox2; pMes-stop Ihh mice) was utilized to assess the consequences of this overexpression on TMJ development during post-natal life. The results showed that the developmental process and expression levels of runt-related transcription factor 2 and sex determining region Y-box 9 in the TMJ of the Wnt1-Cre; pMes-stop shox2; pMes-stop Ihh mice were similar to those in wild‑type mice. Overexpression of Ihh rescued shox2 overexpression-associated reduction of extracellular matrix components. However, overexpression of Ihh did not inhibit the shox2 overexpression-associated increase of matrix metalloproteinases (MMPs) MMP9, MMP13 and apoptosis in the TMJ. These combinatory cellular and molecular defects appeared to account for the observed congenital dysplasia of TMJ, suggesting that overexpression of Ihh partially rescued shox2 overexpression‑associated congenital dysplasia of the TMJ in mice.

  20. Prothymosin α overexpression contributes to the development of pulmonary emphysema

    Science.gov (United States)

    Su, Bing-Hua; Tseng, Yau-Lin; Shieh, Gia-Shing; Chen, Yi-Cheng; Shiang, Ya-Chieh; Wu, Pensee; Li, Kuo-Jung; Yen, Te-Hsin; Shiau, Ai-Li; Wu, Chao-Liang

    2013-01-01

    Emphysema is one of the disease conditions that comprise chronic obstructive pulmonary disease. Prothymosin α transgenic mice exhibit an emphysema phenotype, but the pathophysiological role of prothymosin α in emphysema remains unclear. Here we show that prothymosin α contributes to the pathogenesis of emphysema by increasing acetylation of histones and nuclear factor-kappaB, particularly upon cigarette smoke exposure. We find a positive correlation between prothymosin α levels and the severity of emphysema in prothymosin α transgenic mice and emphysema patients. Prothymosin α overexpression increases susceptibility to cigarette smoke-induced emphysema, and cigarette smoke exposure further enhances prothymosin α expression. We show that prothymosin α inhibits the association of histone deacetylases with histones and nuclear factor-kappaB, and that prothymosin α overexpression increases expression of nuclear factor-kappaB-dependent matrix metalloproteinase 2 and matrix metalloproteinase 9, which are found in the lungs of patients with chronic obstructive pulmonary disease. These results demonstrate the clinical relevance of prothymosin α in regulating acetylation events during the pathogenesis of emphysema. PMID:23695700

  1. Overexpression of host plant urease in transgenic silkworms.

    Science.gov (United States)

    Jiang, Liang; Huang, Chunlin; Sun, Qiang; Guo, Huizhen; Peng, Zhengwen; Dang, Yinghui; Liu, Weiqiang; Xing, Dongxu; Xu, Guowen; Zhao, Ping; Xia, Qingyou

    2015-06-01

    Bombyx mori and mulberry constitute a model of insect-host plant interactions. Urease hydrolyzes urea to ammonia and is important for the nitrogen metabolism of silkworms because ammonia is assimilated into silk protein. Silkworms do not synthesize urease and acquire it from mulberry leaves. We synthesized the artificial DNA sequence ureas using the codon bias of B. mori to encode the signal peptide and mulberry urease protein. A transgenic vector that overexpresses ure-as under control of the silkworm midgut-specific P2 promoter was constructed. Transgenic silkworms were created via embryo microinjection. RT-PCR results showed that urease was expressed during the larval stage and qPCR revealed the expression only in the midgut of transgenic lines. Urea concentration in the midgut and hemolymph of transgenic silkworms was significantly lower than in a nontransgenic line when silkworms were fed an artificial diet. Analysis of the daily body weight and food conversion efficiency of the fourth and fifth instar larvae and economic characteristics indicated no differences between transgenic silkworms and the nontransgenic line. These results suggested that overexpression of host plant urease promoted nitrogen metabolism in silkworms.

  2. c-myc overexpression causes anaplasia in medulloblastoma.

    Science.gov (United States)

    Stearns, Duncan; Chaudhry, Aneeka; Abel, Ty W; Burger, Peter C; Dang, Chi V; Eberhart, Charles G

    2006-01-15

    Both anaplasia and increased c-myc gene expression have been shown to be negative prognostic indicators for survival in medulloblastoma patients. myc gene amplification has been identified in many large cell/anaplastic medulloblastoma, but no causative link between c-myc and anaplastic changes has been established. To address this, we stably overexpressed c-myc in two medulloblastoma cell lines, DAOY and UW228, and examined the changes in growth characteristics. When analyzed in vitro, cell lines with increased levels of c-myc had higher rates of growth and apoptosis as well as significantly improved ability to form colonies in soft agar compared with control. When injected s.c. into nu/nu mice, flank xenograft tumors with high levels of c-myc in DAOY cell line background were 75% larger than those derived from control. Overexpression of c-myc was required for tumor formation by UW228 cells. Most remarkably, the histopathology of the Myc tumors was severely anaplastic, with large areas of necrosis/apoptosis, increased nuclear size, and macronucleoli. Indices of proliferation and apoptosis were also significantly higher in Myc xenografts. Thus, c-myc seems to play a causal role in inducing anaplasia in medulloblastoma. Because anaplastic changes are often observed in recurrent medulloblastoma, we propose that c-myc dysregulation is involved in the progression of these malignant embryonal neoplasms.

  3. Overexpression of neurofilament H disrupts normal cell structure and function

    Science.gov (United States)

    Szebenyi, Gyorgyi; Smith, George M.; Li, Ping; Brady, Scott T.

    2002-01-01

    Studying exogenously expressed tagged proteins in live cells has become a standard technique for evaluating protein distribution and function. Typically, expression levels of experimentally introduced proteins are not regulated, and high levels are often preferred to facilitate detection. However, overexpression of many proteins leads to mislocalization and pathologies. Therefore, for normative studies, moderate levels of expression may be more suitable. To understand better the dynamics of intermediate filament formation, transport, and stability in a healthy, living cell, we inserted neurofilament heavy chain (NFH)-green fluorescent protein (GFP) fusion constructs in adenoviral vectors with tetracycline (tet)-regulated promoters. This system allows for turning on or off the synthesis of NFH-GFP at a selected time, for a defined period, in a dose-dependent manner. We used this inducible system for live cell imaging of changes in filament structure and cell shape, motility, and transport associated with increasing NFH-GFP expression. Cells with low to intermediate levels of NFH-GFP were structurally and functionally similar to neighboring, nonexpressing cells. In contrast, overexpression led to pathological alterations in both filament organization and cell function. Copyright 2002 Wiley-Liss, Inc.

  4. SNEV overexpression extends the life span of human endothelial cells

    International Nuclear Information System (INIS)

    Voglauer, Regina; Chang, Martina Wei-Fen; Dampier, Brigitta; Wieser, Matthias; Baumann, Kristin; Sterovsky, Thomas; Schreiber, Martin; Katinger, Hermann; Grillari, Johannes

    2006-01-01

    In a recent screening for genes downregulated in replicatively senescent human umbilical vein endothelial cells (HUVECs), we have isolated the novel protein SNEV. Since then SNEV has proven as a multifaceted protein playing a role in pre-mRNA splicing, DNA repair, and the ubiquitin/proteosome system. Here, we report that SNEV mRNA decreases in various cell types during replicative senescence, and that it is increased in various immortalized cell lines, as well as in breast tumors, where SNEV transcript levels also correlate with the survival of breast cancer patients. Since these mRNA profiles suggested a role of SNEV in the regulation of cell proliferation, the effect of its overexpression was tested. Thereby, a significant extension of the cellular life span was observed, which was not caused by altered telomerase activity or telomere dynamics but rather by enhanced stress resistance. When SNEV overexpressing cells were treated with bleomycin or bleomycin combined with BSO, inducing DNA damage as well as reactive oxygen species, a significantly lower fraction of apoptotic cells was found in comparison to vector control cells. These data suggest that high levels of SNEV might extend the cellular life span by increasing the resistance to stress or by improving the DNA repair capacity of the cells

  5. A Polynomial Estimate of Railway Line Delay

    DEFF Research Database (Denmark)

    Cerreto, Fabrizio; Harrod, Steven; Nielsen, Otto Anker

    2017-01-01

    Railway service may be measured by the aggregate delay over a time horizon or due to an event. Timetables for railway service may dampen aggregate delay by addition of additional process time, either supplement time or buffer time. The evaluation of these variables has previously been performed...... by numerical analysis with simulation. This paper proposes an analytical estimate of aggregate delay with a polynomial form. The function returns the aggregate delay of a railway line resulting from an initial, primary, delay. Analysis of the function demonstrates that there should be a balance between the two...

  6. Delay Variation Model with Two Service Queues

    Directory of Open Access Journals (Sweden)

    Filip Rezac

    2010-01-01

    Full Text Available Delay in VoIP technology is very unpleasant issue and therefore a voice packets prioritization must be ensured. To maintain the high call quality a maximum information delivery time from the sender to the recipient is set to 150 ms. This paper focuses on the design of a mathematical model of end-to-end delay of a VoIP connection, in particular on a delay variation. It describes all partial delay components and mechanisms, their generation, facilities and mathematical formulations. A new approach to the delay variation model is presented and its validation has been done by experimention.

  7. Fuzzy delay model based fault simulator for crosstalk delay fault test ...

    Indian Academy of Sciences (India)

    In this paper, a fuzzy delay model based crosstalk delay fault simulator is proposed. As design trends move towards nanometer technologies, more number of new parameters affects the delay of the component. Fuzzy delay models are ideal for modelling the uncertainty found in the design and manufacturing steps.

  8. Transgenic overexpression of BAFF regulates the expression of ...

    Indian Academy of Sciences (India)

    LI ZHANG

    animal models could effectively remove B cells, delay the. Keywords. .... sues were crushed in a mortar filled with liquid nitrogen ... The whole body of zebrafish was collected and homoge- ... (Yang et al. ... ating a soluble protein fragment with a molecular weight of ... showed traits of prematurity with a distinct tail and a yolk.

  9. Bcl-2 over-expression fails to prevent age-related loss of calretinin positive neurons in the mouse dentate gyrus

    Directory of Open Access Journals (Sweden)

    Han Mingbo

    2006-08-01

    Full Text Available Abstract Background Cognitive performance declines with increasing age. Possible cellular mechanisms underlying this age-related functional decline remain incompletely understood. Early studies attributed this functional decline to age-related neuronal loss. Subsequent studies using unbiased stereological techniques found little or no neuronal loss during aging. However, studies using specific cellular markers found age-related loss of specific neuronal types. To test whether there is age-related loss of specific neuronal populations in the hippocampus, and subsequently, whether over-expression of the B-cell lymphoma protein-2 (Bcl-2 in these neurons could delay possible age-related neuronal loss, we examined calretinin (CR positive neurons in the mouse dentate gyrus during aging. Result In normal mice, there was an age-related loss of CR positive cells in the dentate gyrus. At the same region, there was no significant decrease of total numbers of neurons, which suggested that age-related loss of CR positive cells was due to the decrease of CR expression in these cells instead of cell death. In the transgenic mouse line over-expressing Bcl-2 in neurons, there was an age-related loss of CR positive cells. Interestingly, there was also an age-related neuronal loss in this transgenic mouse line. Conclusion These data suggest an age-related loss of CR positive neurons but not total neuronal loss in normal mice and this age-related neuronal change is not prevented by Bcl-2 over-expression.

  10. Precise delay measurement through combinatorial logic

    Science.gov (United States)

    Burke, Gary R. (Inventor); Chen, Yuan (Inventor); Sheldon, Douglas J. (Inventor)

    2010-01-01

    A high resolution circuit and method for facilitating precise measurement of on-chip delays for FPGAs for reliability studies. The circuit embeds a pulse generator on an FPGA chip having one or more groups of LUTS (the "LUT delay chain"), also on-chip. The circuit also embeds a pulse width measurement circuit on-chip, and measures the duration of the generated pulse through the delay chain. The pulse width of the output pulse represents the delay through the delay chain without any I/O delay. The pulse width measurement circuit uses an additional asynchronous clock autonomous from the main clock and the FPGA propagation delay can be displayed on a hex display continuously for testing purposes.

  11. Reasons for diagnostic delay in gynecological malignancies

    DEFF Research Database (Denmark)

    Vandborg, Mai Partridge; Christensen, René dePont Christensen; Kragstrup, Jakob

    2011-01-01

    (≤ or > 60 years), performance of gynecological examination by the GP and notification of cancer suspicion on first referral from GP’s on the diagnostic delay (short delay ≤90 days and long delay >90 days). Results Across cancer type a median total delay of 101 days was observed. The 10% of women......Aim The primary aim of this study was to identify and describe different delay types in women with gynecologic cancer, and to analyze the relationship between diagnostic delay and a number of characteristics for patients, cancers and the health care system. Setting A cohort study of women newly......) and The Danish Gynecological Cancer Database (DGCD). 161 women were included; ovarian cancer: 63, endometrial cancer: 50, cervical cancer: 34 and vulvar cancer: 14. Outcome measures were different delay types counted in days and the influence of four clinical important variables: Presence of alarm symptoms, age...

  12. Temperature Dependent Wire Delay Estimation in Floorplanning

    DEFF Research Database (Denmark)

    Winther, Andreas Thor; Liu, Wei; Nannarelli, Alberto

    2011-01-01

    Due to large variations in temperature in VLSI circuits and the linear relationship between metal resistance and temperature, the delay through wires of the same length can be different. Traditional thermal aware floorplanning algorithms use wirelength to estimate delay and routability. In this w......Due to large variations in temperature in VLSI circuits and the linear relationship between metal resistance and temperature, the delay through wires of the same length can be different. Traditional thermal aware floorplanning algorithms use wirelength to estimate delay and routability....... In this work, we show that using wirelength as the evaluation metric does not always produce a floorplan with the shortest delay. We propose a temperature dependent wire delay estimation method for thermal aware floorplanning algorithms, which takes into account the thermal effect on wire delay. The experiment...

  13. Elite athletes and pubertal delay.

    Science.gov (United States)

    Kapczuk, Karina

    2017-10-01

    Intensive physical training and participation in competitive sports during childhood and early adolescence may affect athletes' pubertal development. On the other hand, pubertal timing, early or late, may impact on an athlete selection for a particular sport. Genetic predisposition, training load, nutritional status and psychological stress determine athletes' pubertal timing. Athletes that practice esthetic sports, especially gymnasts, are predisposed to a delay in pubertal development. The growing evidence indicates that energy deficiency, not a systemic training per se, plays a crucial role in the pathogenesis of functional hypothalamic hypogonadism in female athletes. Metabolic and psychologic stress activate hypothalamic-pituitary-adrenal axis and suppress hypothalamic-pituitary-ovarian axis. Female athletes who do not begin secondary sexual development by the age of 14 or menstruation by the age of 16 warrant a comprehensive evaluation and a targeted treatment. Somatic growth and sexual maturation of elite female athletes are largely sport-specific since each sport favors a particular somatotype and requires a specific training. Chronic negative energy balance resulting from a systemic physical training and inadequate energy intake may delay pubertal development in elite athletes. Youth athletes, especially those engaged in competitive sports that emphasize prepubertal or lean appearance, are at risk of developing relative energy deficiency in sport associated with disordered eating or eating disorders. Management strategies should address the complex conditions underlying functional hypothalamic hypogonadism.

  14. Delayed recombination and cosmic parameters

    International Nuclear Information System (INIS)

    Galli, Silvia; Melchiorri, Alessandro; Bean, Rachel; Silk, Joseph

    2008-01-01

    Current cosmological constraints from cosmic microwave background anisotropies are typically derived assuming a standard recombination scheme, however additional resonance and ionizing radiation sources can delay recombination, altering the cosmic ionization history and the cosmological inferences drawn from the cosmic microwave background data. We show that for recent observations of the cosmic microwave background anisotropy, from the Wilkinson microwave anisotropy probe satellite mission (WMAP) 5-year survey and from the arcminute cosmology bolometer array receiver experiment, additional resonance radiation is nearly degenerate with variations in the spectral index, n s , and has a marked effect on uncertainties in constraints on the Hubble constant, age of the universe, curvature and the upper bound on the neutrino mass. When a modified recombination scheme is considered, the redshift of recombination is constrained to z * =1078±11, with uncertainties in the measurement weaker by 1 order of magnitude than those obtained under the assumption of standard recombination while constraints on the shift parameter are shifted by 1σ to R=1.734±0.028. From the WMAP5 data we obtain the following constraints on the resonance and ionization sources parameters: ε α i <0.058 at 95% c.l.. Although delayed recombination limits the precision of parameter estimation from the WMAP satellite, we demonstrate that this should not be the case for future, smaller angular scales measurements, such as those by the Planck satellite mission.

  15. Asymptotic Delay Analysis for Cross-Layer Delay-Based Routing in Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    Philippe Jacquet

    2007-01-01

    Full Text Available This paper addresses the problem of the evaluation of the delay distribution via analytical means in IEEE 802.11 wireless ad hoc networks. We show that the asymptotic delay distribution can be expressed as a power law. Based on the latter result, we present a cross-layer delay estimation protocol and we derive new delay-distribution-based routing algorithms, which are well adapted to the QoS requirements of real-time multimedia applications. In fact, multimedia services are not sensitive to average delays, but rather to the asymptotic delay distributions. Indeed, video streaming applications drop frames when they are received beyond a delay threshold, determined by the buffer size. Although delay-distribution-based routing is an NP-hard problem, we show that it can be solved in polynomial time when the delay threshold is large, because of the asymptotic power law distribution of the link delays.

  16. Electrical remodeling of cardiac myocytes from mice with heart failure due to the overexpression of tumor necrosis factor-alpha.

    Science.gov (United States)

    Petkova-Kirova, Polina S; Gursoy, Erdal; Mehdi, Haider; McTiernan, Charles F; London, Barry; Salama, Guy

    2006-05-01

    Mice that overexpress the inflammatory cytokine tumor necrosis factor-alpha in the heart (TNF mice) develop heart failure characterized by atrial and ventricular dilatation, decreased ejection fraction, atrial and ventricular arrhythmias, and increased mortality (males > females). Abnormalities in Ca2+ handling, prolonged action potential duration (APD), calcium alternans, and reentrant atrial and ventricular arrhythmias were previously observed with the use of optical mapping of perfused hearts from TNF mice. We therefore tested whether altered voltage-gated outward K+ and/or inward Ca2+ currents contribute to the altered action potential characteristics and the increased vulnerability to arrhythmias. Whole cell voltage-clamp recordings of K+ currents from left ventricular myocytes of TNF mice revealed an approximately 50% decrease in the rapidly activating, rapidly inactivating transient outward K+ current Ito and in the rapidly activating, slowly inactivating delayed rectifier current IK,slow1, an approximately 25% decrease in the rapidly activating, slowly inactivating delayed rectifier current IK,slow2, and no significant change in the steady-state current Iss compared with controls. Peak amplitudes and inactivation kinetics of the L-type Ca2+ current ICa,L were not altered. Western blot analyses revealed a reduction in the proteins underlying Kv4.2, Kv4.3, and Kv1.5. Thus decreased K+ channel expression is largely responsible for the prolonged APD in the TNF mice and may, along with abnormalities in Ca2+ handling, contribute to arrhythmias.

  17. Del-1 overexpression potentiates lung cancer cell proliferation and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung-Hwan; Kim, Dong-Young; Jing, Feifeng; Kim, Hyesoon [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Yun, Chae-Ok [Department of Bioengineering, College of Engineering, Hanyang University, Seoul (Korea, Republic of); Han, Deok-Jong [Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Choi, Eun Young, E-mail: choieun@ulsan.ac.kr [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2015-12-04

    Developmental endothelial locus-1 (Del-1) is an endogenous anti-inflammatory molecule that is highly expressed in the lung and the brain and limits leukocyte migration to these tissues. We previously reported that the expression of Del-1 is positively regulated by p53 in lung endothelial cells. Although several reports have implicated the altered expression of Del-1 gene in cancer patients, little is known about its role in tumor cells. We here investigated the effect of Del-1 on the features of human lung carcinoma cells. Del-1 mRNA was found to be significantly decreased in the human lung adenocarcinoma cell lines A549 (containing wild type of p53), H1299 (null for p53) and EKVX (mutant p53), compared to in human normal lung epithelial BEAS-2B cells and MRC-5 fibroblasts. The decrease of Del-1 expression was dependent on the p53 activity in the cell lines, but not on the expression of p53. Neither treatment with recombinant human Del-1 protein nor the introduction of adenovirus expressing Del-1 altered the expression of the apoptosis regulators BAX, PUMA and Bcl-2. Unexpectedly, the adenovirus-mediated overexpression of Del-1 gene into the lung carcinoma cell lines promoted proliferation and invasion of the lung carcinoma cells, as revealed by BrdU incorporation and transwell invasion assays, respectively. In addition, overexpression of the Del-1 gene enhanced features of epithelial–mesenchymal transition (EMT), such as increasing vimentin while decreasing E-cadherin in A549 cells, and increases in the level of Slug, an EMT-associated transcription regulator. Our findings demonstrated for the first time that there are deleterious effects of high levels of Del-1 in lung carcinoma cells, and suggest that Del-1 may be used as a diagnostic or prognostic marker for cancer progression, and as a novel therapeutic target for lung carcinoma. - Highlights: • Developmental Endothelial Locus-1 (Del-1) expression is downregulated in human lung cancer cells.

  18. Del-1 overexpression potentiates lung cancer cell proliferation and invasion

    International Nuclear Information System (INIS)

    Lee, Seung-Hwan; Kim, Dong-Young; Jing, Feifeng; Kim, Hyesoon; Yun, Chae-Ok; Han, Deok-Jong; Choi, Eun Young

    2015-01-01

    Developmental endothelial locus-1 (Del-1) is an endogenous anti-inflammatory molecule that is highly expressed in the lung and the brain and limits leukocyte migration to these tissues. We previously reported that the expression of Del-1 is positively regulated by p53 in lung endothelial cells. Although several reports have implicated the altered expression of Del-1 gene in cancer patients, little is known about its role in tumor cells. We here investigated the effect of Del-1 on the features of human lung carcinoma cells. Del-1 mRNA was found to be significantly decreased in the human lung adenocarcinoma cell lines A549 (containing wild type of p53), H1299 (null for p53) and EKVX (mutant p53), compared to in human normal lung epithelial BEAS-2B cells and MRC-5 fibroblasts. The decrease of Del-1 expression was dependent on the p53 activity in the cell lines, but not on the expression of p53. Neither treatment with recombinant human Del-1 protein nor the introduction of adenovirus expressing Del-1 altered the expression of the apoptosis regulators BAX, PUMA and Bcl-2. Unexpectedly, the adenovirus-mediated overexpression of Del-1 gene into the lung carcinoma cell lines promoted proliferation and invasion of the lung carcinoma cells, as revealed by BrdU incorporation and transwell invasion assays, respectively. In addition, overexpression of the Del-1 gene enhanced features of epithelial–mesenchymal transition (EMT), such as increasing vimentin while decreasing E-cadherin in A549 cells, and increases in the level of Slug, an EMT-associated transcription regulator. Our findings demonstrated for the first time that there are deleterious effects of high levels of Del-1 in lung carcinoma cells, and suggest that Del-1 may be used as a diagnostic or prognostic marker for cancer progression, and as a novel therapeutic target for lung carcinoma. - Highlights: • Developmental Endothelial Locus-1 (Del-1) expression is downregulated in human lung cancer cells.

  19. Effect of Rad 51 overexpression on chromosomal stability and radiation sensitivity in tumour cells

    International Nuclear Information System (INIS)

    Jend, C.; Stuerzbecher, H.W.; Dikomey, E.; Borgmann, K.

    2004-01-01

    The present study was dedicated to examining the effects of Rad51 overexpression on genomic instability, expressed in terms of chromosomal aberrations in G1 and G2 phases following X-ray irradiation. For this purpose an osteosarcoma cell line (Ui-OS) which shows inducing Rad51 overexpression (UiRad5-2) after stable transfection was compared with an isogenetic line (UiLacZ) which overexpresses beta-galactosidase instead of Rad51 [de

  20. Absence of Nrf2 or its selective overexpression in neurons and muscle does not affect survival in ALS-linked mutant hSOD1 mouse models.

    Directory of Open Access Journals (Sweden)

    Marcelo R Vargas

    Full Text Available The nuclear factor erythroid 2-related factor 2 (Nrf2 governs the expression of antioxidant and phase II detoxifying enzymes. Nrf2 activation can prevent or reduce cellular damage associated with several types of injury in many different tissues and organs. Dominant mutations in Cu/Zn-superoxide dismutase (SOD1 cause familial forms of amyotrophic lateral sclerosis (ALS, a fatal disorder characterized by the progressive loss of motor neurons and subsequent muscular atrophy. We have previously shown that Nrf2 activation in astrocytes delays neurodegeneration in ALS mouse models. To further investigate the role of Nrf2 in ALS we determined the effect of absence of Nrf2 or its restricted overexpression in neurons or type II skeletal muscle fibers on symptoms onset and survival in mutant hSOD1 expressing mice. We did not observe any detrimental effect associated with the lack of Nrf2 in two different mutant hSOD1 animal models of ALS. However, restricted Nrf2 overexpression in neurons or type II skeletal muscle fibers delayed disease onset but failed to extend survival in hSOD1(G93A mice. These results highlight the concept that not only the pharmacological target but also the cell type targeted may be relevant when considering a Nrf2-mediated therapeutic approach for ALS.

  1. The novel triterpenoid RTA 408 protects human retinal pigment epithelial cells against H2O2-induced cell injury via NF-E2-related factor 2 (Nrf2 activation

    Directory of Open Access Journals (Sweden)

    Xiaobin Liu

    2016-08-01

    Full Text Available Oxidative stress-induced retinal pigment epithelial (RPE cell damage is an important factor in the pathogenesis of age-related macular degeneration (AMD. Previous studies have shown that RTA 408, a synthetic triterpenoid compound, potently activates Nrf2. This study aimed to investigate the protective effects of RTA 408 in cultured RPE cells during oxidative stress and to determine the effects of RTA 408 on Nrf2 and its downstream target genes. Primary human RPE cells were pretreated with RTA 408 and then incubated in 200 μM H2O2 for 6 h. Cell viability was measured with the WST-8 assay. Apoptosis was quantitatively measured by annexin V/propidium iodide (PI double staining and Hoechst 33342 fluorescent staining. Reduced (GSH and oxidized glutathione (GSSG were measured using colorimetric assays. Nrf2 activation and its downstream effects on phase II enzymes were examined by Western blot. Treatment of RPE cells with nanomolar ranges (10 and 100 nM of RTA 408 markedly attenuated H2O2-induced viability loss and apoptosis. RTA 408 pretreatment significantly protected cells from oxidative stress-induced GSH loss, GSSG formation and decreased ROS production. RTA 408 activated Nrf2 and increased the expression of its downstream genes, such as HO-1, NQO1, SOD2, catalase, Grx1, and Trx1. Consequently, the enzyme activities of NQO1, Grx1, and Trx1 were fully protected by RTA 408 pretreatment under oxidative stress. Moreover, knockdown of Nrf2 by siRNA significantly reduced the cytoprotective effects of RTA 408. In conclusion, our data suggest that RTA 408 protect primary human RPE cells from oxidative stress-induced damage by activating Nrf2 and its downstream genes.

  2. ADAM12 overexpression does not improve outcome in mice with laminin alpha2-deficient muscular dystrophy

    DEFF Research Database (Denmark)

    Guo, Ling T; Shelton, G Diane; Wewer, Ulla M

    2005-01-01

    We have recently shown that overexpression of ADAM12 results in increased muscle regeneration and significantly reduced pathology in mdx, dystrophin deficient mice. In the present study, we tested the effect of overexpressing ADAM12 in dy(W) laminin-deficient mice. dy mice have a very severe...... clinical phenotype and would be expected to benefit greatly from enhanced regeneration. We found that dy(W) mice overexpressing ADAM12 indeed have increased muscle regeneration, as evidenced by increased numbers of muscle fibers expressing fetal myosin. However, overexpression of ADAM12 had no significant...

  3. Mammary gland tumor formation in transgenic mice overexpressing stromelysin-1

    Energy Technology Data Exchange (ETDEWEB)

    Sympson, Carolyn J; Bissell, Mina J; Werb, Zena

    1995-06-01

    An intact basement membrane (BM) is essential for the proper function, differentiation and morphology of many epithelial cells. The disruption or loss of this BM occurs during normal development as well as in the disease state. To examine the importance of BM during mammary gland development in vivo, we generated transgenic mice that inappropriately express autoactivating isoforms of the matrix metalloproteinase stromelysin-1. The mammary glands from these mice are both functionally and morphologically altered throughout development. We have now documented a dramatic incidence of breast tumors in several independent lines of these mice. These data suggest that overexpression of stromelysin-1 and disruption of the BM may be a key step in the multi-step process of breast cancer.

  4. Nicotinamide phosphoribosyltransferase delays cellular senescence by upregulating SIRT1 activity and antioxidant gene expression in mouse cells.

    Science.gov (United States)

    Khaidizar, Fiqri D; Nakahata, Yasukazu; Kume, Akira; Sumizawa, Kyosuke; Kohno, Kenji; Matsui, Takaaki; Bessho, Yasumasa

    2017-12-01

    Senescent cells accumulate in tissues of aged animals and deteriorate tissue functions. The elimination of senescent cells from aged mice not only attenuates progression of already established age-related disorders, but also extends median lifespan. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in mammalian NAD + salvage pathway, has shown a protective effect on cellular senescence of human primary cells. However, it still remains unclear how NAMPT has a protective impact on aging in vitro and in vivo. In this study, we found that primary mouse embryonic fibroblast (MEF) cells undergo progressive decline of NAMPT and NAD + contents during serial passaging before becoming senescent. Furthermore, we showed that constitutive Nampt over-expression increases cellular NAD + content and delays cellular senescence of MEF cells in vitro. We further found that constitutive Nampt over-expression increases SIRT1 activity, increases the expression of antioxidant genes, superoxide dismutase 2 and catalase and promotes resistance against oxidative stress. These findings suggest that Nampt over-expression in MEF cells delays cellular senescence by the mitigation of oxidative stress via the upregulation of superoxide dismutase 2 and catalase gene expressions by SIRT1 activation. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  5. Fascin overexpression promotes neoplastic progression in oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Alam Hunain

    2012-01-01

    Full Text Available Abstract Background Fascin is a globular actin cross-linking protein, which plays a major role in forming parallel actin bundles in cell protrusions and is found to be associated with tumor cell invasion and metastasis in various type of cancers including oral squamous cell carcinoma (OSCC. Previously, we have demonstrated that fascin regulates actin polymerization and thereby promotes cell motility in K8-depleted OSCC cells. In the present study we have investigated the role of fascin in tumor progression of OSCC. Methods To understand the role of fascin in OSCC development and/or progression, fascin was overexpressed along with vector control in OSCC derived cells AW13516. The phenotype was studied using wound healing, Boyden chamber, cell adhesion, Hanging drop, soft agar and tumorigenicity assays. Further, fascin expression was examined in human OSCC samples (N = 131 using immunohistochemistry and level of its expression was correlated with clinico-pathological parameters of the patients. Results Fascin overexpression in OSCC derived cells led to significant increase in cell migration, cell invasion and MMP-2 activity. In addition these cells demonstrated increased levels of phosphorylated AKT, ERK1/2 and JNK1/2. Our in vitro results were consistent with correlative studies of fascin expression with the clinico-pathological parameters of the OSCC patients. Fascin expression in OSCC showed statistically significant correlation with increased tumor stage (P = 0.041, increased lymph node metastasis (P = 0.001, less differentiation (P = 0.005, increased recurrence (P = 0.038 and shorter survival (P = 0.004 of the patients. Conclusion In conclusion, our results indicate that fascin promotes tumor progression and activates AKT and MAPK pathways in OSCC-derived cells. Further, our correlative studies of fascin expression in OSCC with clinico-pathological parameters of the patients indicate that fascin may prove to be useful in prognostication and

  6. Tubular overexpression of gremlin induces renal damage susceptibility in mice.

    Directory of Open Access Journals (Sweden)

    Alejandra Droguett

    Full Text Available A growing number of patients are recognized worldwide to have chronic kidney disease. Glomerular and interstitial fibrosis are hallmarks of renal progression. However, fibrosis of the kidney remains an unresolved challenge, and its molecular mechanisms are still not fully understood. Gremlin is an embryogenic gene that has been shown to play a key role in nephrogenesis, and its expression is generally low in the normal adult kidney. However, gremlin expression is elevated in many human renal diseases, including diabetic nephropathy, pauci-immune glomerulonephritis and chronic allograft nephropathy. Several studies have proposed that gremlin may be involved in renal damage by acting as a downstream mediator of TGF-β. To examine the in vivo role of gremlin in kidney pathophysiology, we generated seven viable transgenic mouse lines expressing human gremlin (GREM1 specifically in renal proximal tubular epithelial cells under the control of an androgen-regulated promoter. These lines demonstrated 1.2- to 200-fold increased GREM1 expression. GREM1 transgenic mice presented a normal phenotype and were without proteinuria and renal function involvement. In response to the acute renal damage cause by folic acid nephrotoxicity, tubule-specific GREM1 transgenic mice developed increased proteinuria after 7 and 14 days compared with wild-type treated mice. At 14 days tubular lesions, such as dilatation, epithelium flattening and hyaline casts, with interstitial cell infiltration and mild fibrosis were significantly more prominent in transgenic mice than wild-type mice. Tubular GREM1 overexpression was correlated with the renal upregulation of profibrotic factors, such as TGF-β and αSMA, and with increased numbers of monocytes/macrophages and lymphocytes compared to wild-type mice. Taken together, our results suggest that GREM1-overexpressing mice have an increased susceptibility to renal damage, supporting the involvement of gremlin in renal damage

  7. Fascin overexpression promotes neoplastic progression in oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Alam, Hunain; Kannanl, Sadhna; Gude, Rajiv; Kane, Shubhada; Dalal, Sorab N; Vaidya, Milind M; Bhate, Amruta V; Gangadaran, Prakash; Sawant, Sharda S; Salot, Shimul; Sehgal, Lalit; Dange, Prerana P; Chaukar, Devendra A; D'cruz, Anil K

    2012-01-01

    Fascin is a globular actin cross-linking protein, which plays a major role in forming parallel actin bundles in cell protrusions and is found to be associated with tumor cell invasion and metastasis in various type of cancers including oral squamous cell carcinoma (OSCC). Previously, we have demonstrated that fascin regulates actin polymerization and thereby promotes cell motility in K8-depleted OSCC cells. In the present study we have investigated the role of fascin in tumor progression of OSCC. To understand the role of fascin in OSCC development and/or progression, fascin was overexpressed along with vector control in OSCC derived cells AW13516. The phenotype was studied using wound healing, Boyden chamber, cell adhesion, Hanging drop, soft agar and tumorigenicity assays. Further, fascin expression was examined in human OSCC samples (N = 131) using immunohistochemistry and level of its expression was correlated with clinico-pathological parameters of the patients. Fascin overexpression in OSCC derived cells led to significant increase in cell migration, cell invasion and MMP-2 activity. In addition these cells demonstrated increased levels of phosphorylated AKT, ERK1/2 and JNK1/2. Our in vitro results were consistent with correlative studies of fascin expression with the clinico-pathological parameters of the OSCC patients. Fascin expression in OSCC showed statistically significant correlation with increased tumor stage (P = 0.041), increased lymph node metastasis (P = 0.001), less differentiation (P = 0.005), increased recurrence (P = 0.038) and shorter survival (P = 0.004) of the patients. In conclusion, our results indicate that fascin promotes tumor progression and activates AKT and MAPK pathways in OSCC-derived cells. Further, our correlative studies of fascin expression in OSCC with clinico-pathological parameters of the patients indicate that fascin may prove to be useful in prognostication and treatment of OSCC

  8. Dynamics of Nonlinear Time-Delay Systems

    CERN Document Server

    Lakshmanan, Muthusamy

    2010-01-01

    Synchronization of chaotic systems, a patently nonlinear phenomenon, has emerged as a highly active interdisciplinary research topic at the interface of physics, biology, applied mathematics and engineering sciences. In this connection, time-delay systems described by delay differential equations have developed as particularly suitable tools for modeling specific dynamical systems. Indeed, time-delay is ubiquitous in many physical systems, for example due to finite switching speeds of amplifiers in electronic circuits, finite lengths of vehicles in traffic flows, finite signal propagation times in biological networks and circuits, and quite generally whenever memory effects are relevant. This monograph presents the basics of chaotic time-delay systems and their synchronization with an emphasis on the effects of time-delay feedback which give rise to new collective dynamics. Special attention is devoted to scalar chaotic/hyperchaotic time-delay systems, and some higher order models, occurring in different bran...

  9. Group Delay of High Q Antennas

    DEFF Research Database (Denmark)

    Bahramzy, Pevand; Pedersen, Gert Frølund

    2013-01-01

    Group Delay variations versus frequency is an essential factor which can cause distortion and degradation in the signals. Usually this is an issue in wideband communication systems, such as satellite communication systems, which are used for transmitting wideband data. However, group delay can also...... become an issue, when working with high Q antennas, because of the steep phase shift over the frequency. In this paper, it is measured how large group delay variations can become, when going from a low Q antenna to a high Q antenna. The group delay of a low Q antenna is shown to be around 1.3 ns, whereas...... a high Q antenna has group delay of around 22 ns. It is due to this huge group delay variation characteristics of high Q antennas, that signal distortion might occur in the radio system with high Q antennas....

  10. Permutation entropy with vector embedding delays

    Science.gov (United States)

    Little, Douglas J.; Kane, Deb M.

    2017-12-01

    Permutation entropy (PE) is a statistic used widely for the detection of structure within a time series. Embedding delay times at which the PE is reduced are characteristic timescales for which such structure exists. Here, a generalized scheme is investigated where embedding delays are represented by vectors rather than scalars, permitting PE to be calculated over a (D -1 ) -dimensional space, where D is the embedding dimension. This scheme is applied to numerically generated noise, sine wave and logistic map series, and experimental data sets taken from a vertical-cavity surface emitting laser exhibiting temporally localized pulse structures within the round-trip time of the laser cavity. Results are visualized as PE maps as a function of embedding delay, with low PE values indicating combinations of embedding delays where correlation structure is present. It is demonstrated that vector embedding delays enable identification of structure that is ambiguous or masked, when the embedding delay is constrained to scalar form.

  11. Delays in the management of retroperitoneal sarcomas

    DEFF Research Database (Denmark)

    Seinen, Jojanneke; Almquist, Martin; Styring, Emelie

    2010-01-01

    Retroperitoneal sarcomas are rare and treatment should optimally be centralized. Despite successful centralization with 90% of the patients referred prior to surgery, delays occur, which led us to assess lead times in a population-based series. Method. Patients diagnosed with retroperitoneal...... sarcoma in the southern Sweden health care region 2003-2009 were eligible for the study. Data on referrals and diagnostic investigations were collected from clinical files from primary health care, local hospitals, and from the sarcoma centre. Lead times were divided into patient delays and health care...... delays caused by primary health care, local hospitals, or procedures at the sarcoma centre. Results. Complete data were available from 33 patients and demonstrated a median patient delay of 23¿days (0-17¿months) and median health care delay of 94¿days (1-40¿months) with delays of median 15¿days...

  12. Time Delay Estimation Algoritms for Echo Cancellation

    Directory of Open Access Journals (Sweden)

    Kirill Sakhnov

    2011-01-01

    Full Text Available The following case study describes how to eliminate echo in a VoIP network using delay estimation algorithms. It is known that echo with long transmission delays becomes more noticeable to users. Thus, time delay estimation, as a part of echo cancellation, is an important topic during transmission of voice signals over packetswitching telecommunication systems. An echo delay problem associated with IP-based transport networks is discussed in the following text. The paper introduces the comparative study of time delay estimation algorithm, used for estimation of the true time delay between two speech signals. Experimental results of MATLab simulations that describe the performance of several methods based on cross-correlation, normalized crosscorrelation and generalized cross-correlation are also presented in the paper.

  13. CGI delay compensation. [Computer Generated Image

    Science.gov (United States)

    Mcfarland, R. E.

    1986-01-01

    Computer-generated graphics in real-time helicopter simulation produces objectionable scene-presentation time delays. In the flight simulation laboratory at Ames Research Center, it has been determined that these delays have an adverse influence on pilot performance during agressive tasks such as nap of the earth (NOE) maneuvers. Using contemporary equipment, computer generated image (CGI) time delays are an unavoidable consequence of the operations required for scene generation. However, providing that magnitude distortions at higher frequencies are tolerable, delay compensation is possible over a restricted frequency range. This range, assumed to have an upper limit of perhaps 10 or 15 rad/sec, conforms approximately to the bandwidth associated with helicopter handling qualities research. A compensation algorithm is introduced here and evaluated in terms of tradeoffs in frequency responses. The algorithm has a discrete basis and accommodates both a large, constant transport delay interval and a periodic delay interval, as associated with asynchronous operations.

  14. Memorized discrete systems and time-delay

    CERN Document Server

    Luo, Albert C J

    2017-01-01

    This book examines discrete dynamical systems with memory—nonlinear systems that exist extensively in biological organisms and financial and economic organizations, and time-delay systems that can be discretized into the memorized, discrete dynamical systems. It book further discusses stability and bifurcations of time-delay dynamical systems that can be investigated through memorized dynamical systems as well as bifurcations of memorized nonlinear dynamical systems, discretization methods of time-delay systems, and periodic motions to chaos in nonlinear time-delay systems. The book helps readers find analytical solutions of MDS, change traditional perturbation analysis in time-delay systems, detect motion complexity and singularity in MDS; and determine stability, bifurcation, and chaos in any time-delay system.

  15. Magnetic pulse sharpener and delay-line

    International Nuclear Information System (INIS)

    Li Jin; Dai Guangsen; Xia Liansheng

    2002-01-01

    This paper describes a method to achieve short rise time pulse which has been delayed with a delay-line and magnetic pulse sharpener. A delay-line and two shock-lines are designed to carry pulsed signal with a maximum voltage magnitude up to 80 kV. A pulse of High voltage with arise time of 48 ns at a level of 0.1%-0.9% were achieved, and the attenuation in the line is very small

  16. Does Bilingualism Delay the Development of Dementia?

    OpenAIRE

    Amy L Atkinson

    2016-01-01

    It has been suggested that bilingualism (where individuals speak two languages) may delay the development of dementia. However, much of the research is inconclusive. Some researchers have reported that bilingualism delays the onset and diagnosis of dementia, whilst other studies have found weak or even detrimental effects. This paper reviews a series of nine empirical studies, published up until March 2016, which investigated whether bilingualism significantly delays the onset of dementia. Th...

  17. Delayed enhanced MRI in intraparenchymal tumors

    International Nuclear Information System (INIS)

    Eguchi, Takahiko; Morimoto, Tetsuya; Takeshima, Toshikazu

    1991-01-01

    Delayed enhanced MRI was performed on 20 intraparenchymal tumors, and these findings were compared with those of early enhanced MRI. Using the spin-echo technique (SE: 400-500/20 msec), early scans were obtained 5 minutes, and delayed scans were obtained 60 minutes, after the intravenous injection of 0.1 nmol of gadolinium-DTPA/Kg. We discussed the changes in the delayed scan with regard to the change in the pattern of enhancement and the boundary of enhancement. In these twenty intraparenchymal tumors, there were three low-grade astrocytomas, two anaplastic astrocytomas, seven glioblastomas, and eight metastatic tumors. The changes in the enhanced pattern showed three types as follows: Type I: heterogeneous enhancement in both early and delayed scans; Type II: heterogeneous enhancement in early scan and homogeneous enhancement in delayed scan; Type III: homogeneous enhancement in both early and delayed scans. Most malignant tumors, such as glioblastomas (6/8), anaplastic astrocytomas (2/2), and metastatic tumors (7/8), revealed Type I, although low-grade astrocytomas showed Type II (3/2) and Type III (1/3). The heterogeneous enhancement in delayed scan was found in malignant tumors and in low-grade astrocytoma; even if the early scan revealed heterogeneous enhancement, the delayed scan showed homogeneous enhancement. In the delayed scan, most enhanced boundaries spread out of the boundaries in the early scan. Glioblastomas spread markedly in the delayed scan, although none of the low-grade astrocytomas, anaplastic astrocytomas, or metastases revealed marked spreading. We called these marked increases in the delayed scan a 'spreading sign' and thought that this sign was specific to glioblastomas. Recently some authors have emphasized the usefulness of serial scans. Delayed enhanced MRI 60 minutes after the administration of a contrast medium was here found also to be useful for the accurate diagnosis for brain tumors. (author)

  18. Overexpression of prostate tumor overexpressed 1 correlates with tumor progression and predicts poor prognosis in breast cancer

    International Nuclear Information System (INIS)

    Lei, Fangyong; Zhang, Longjuan; Li, Xinghua; Lin, Xi; Wu, Shu; Li, Fengyan; Liu, Junling

    2014-01-01

    Prostate tumor overexpressed 1 (PTOV1) was demonstrated to play an important role in cancer progression and was correlated with unfavorable clinical outcome. However, the clinical role of PTOV1 in cancer remains largely unknown. This study aimed to investigate the expression and clinicopathological significance of PTOV1 in breast cancer. The mRNA and protein expression levels of PTOV1 were analyzed in 12 breast cancer cell lines and eight paired breast cancer tumors by semi-quantitative real time-PCR and western blotting, respectively. Immunohistochemistry was performed to assess PTOV1 protein expression in 169 paraffin-embedded, archived breast cancer samples. Survival analysis and Cox regression analysis were performed to investigate the clinicopathological significance of PTOV1 expression. Our data revealed that PTOV1 was frequently overexpressed in breast cancer cell lines compared to normal human breast epithelial cells and in primary breast cancer samples compared to adjacent noncancerous breast tissues, at both the mRNA and protein levels. Moreover, high expression of PTOV1 in breast cancer is strongly associated with clinicopathological characteristics and estrogen receptor expression status (P = 0.003). Breast cancer patients with higher PTOV1 expression had substantially shorter survival times than patients with lower PTOV1 expression (P < 0.001). Univariate and multivariate analysis revealed that PTOV1 might be an independent prognostic factor for breast cancer patients (P = 0.005). Our study showed that PTOV1 is upregulated in breast cancer cell lines and clinical samples, and its expression was positively associated with progression and aggressiveness of breast cancer, suggesting that PTOV1 could serve as an independent prognostic marker

  19. Neutron stochastic transport theory with delayed neutrons

    International Nuclear Information System (INIS)

    Munoz-Cobo, J.L.; Verdu, G.

    1987-01-01

    From the stochastic transport theory with delayed neutrons, the Boltzmann transport equation with delayed neutrons for the average flux emerges in a natural way without recourse to any approximation. From this theory a general expression is obtained for the Feynman Y-function when delayed neutrons are included. The single mode approximation for the particular case of a subcritical assembly is developed, and it is shown that Y-function reduces to the familiar expression quoted in many books, when delayed neutrons are not considered, and spatial and source effects are not included. (author)

  20. Clinicopathological correlation and prognostic significance of sonic hedgehog protein overexpression in human gastric cancer.

    Science.gov (United States)

    Niu, Yanyang; Li, Fang; Tang, Bo; Shi, Yan; Hao, Yingxue; Yu, Peiwu

    2014-01-01

    This study investigated the expression of Sonic Hedgehog (Shh) protein in gastric cancer, and correlated it with clinicopathological parameters. The prognostic significance of Shh protein was analyzed. Shh protein expression was evaluated in 113 cases of gastric cancer and 60 cases of normal gastric mucosa. The immunoreactivity was scored semi quantitatively as: 0 = absent; 1 = weak; 2 = moderate; and 3 = strong. All cases were further classified into two groups, namely non-overexpression group with score 0 or 1, and overexpression group with score 2 or 3. The overexpression of Shh protein was correlated with clinicopathological parameters. Survival analysis was then performed to determine the Shh protein prognostic significance in gastric cancer. In immunohistochemistry study, nineteen (31.7%) normal gastric mucosa revealed Shh protein overexpression, while eighty-one (71.7%) gastric cancer revealed overexpression. The expression of Shh protein were significantly higher in gastric cancer tissues than in normal gastric mucosa (P overexpression and non-expression groups P = 0.168 and 0.071). However, Shh overexpression emerged as a significant independent prognostic factor in multivariate Cox regression analysis (hazard ratio 1.187, P = 0.041). Shh protein expression is upregulated and is statistically correlated with age, tumor differentiation, depth of invasion, pathologic staging, and nodal metastasis. The Shh protein overexpression is a significant independent prognostic factor in multivariate Cox regression analysis in gastric cancer.

  1. Transcription factors and molecular epigenetic marks underlying EpCAM overexpression in ovarian cancer

    NARCIS (Netherlands)

    van der Gun, B. T. F.; de Groote, M. L.; Kazemier, H. G.; Arendzen, A. J.; Terpstra, P.; Ruiters, M. H. J.; McLaughlin, P. M. J.; Rots, M. G.

    2011-01-01

    BACKGROUND: The epithelial cell adhesion molecule (EpCAM) is overexpressed on carcinomas, and its downregulation inhibits the oncogenic potential of multiple tumour types. Here, we investigated underlying mechanisms of epcam overexpression in ovarian carcinoma. METHODS: Expression of EpCAM and DNA

  2. Over-expression of HER-2 is associated with the stage in ...

    African Journals Online (AJOL)

    Background: The frequency of over-expression of human epidermal growth factor receptor-2 (HER-2) in bladder cancer is one of the highest among all human malignancies. This over-expression is thought to play a role in aberrant proliferation of cancer cells. Studies on HER-2 expression in bladder carcinoma have shown ...

  3. Bone turnover is altered in transgenic rats overexpressing the P2Y2 purinergic receptor

    DEFF Research Database (Denmark)

    Ellegaard, Maria; Agca, Cansu; Petersen, Solveig

    2017-01-01

    overexpression on bone status and bone cell function using a transgenic rat. Three-month-old female transgenic Sprague Dawley rats overexpressing P2Y2R (P2Y2R-Tg) showed higher bone strength of the femoral neck. Histomorphometry showed increase in resorptive surfaces and reduction in mineralizing surfaces. Both...

  4. Correlation between human papillomavirus and p16 overexpression in oropharyngeal tumours

    DEFF Research Database (Denmark)

    Grønhøj Larsen, C; Gyldenløve, M; Jensen, D H

    2014-01-01

    A significant proportion of squamous cell carcinomas of the oropharynx (OP-SCC) are related to human papillomavirus (HPV) infection and p16 overexpression. This subgroup proves better prognosis and survival but no evidence exists on the correlation between HPV and p16 overexpression based on diag...

  5. Long-term polarization of microglia upon alpha-synuclein overexpression in nonhuman primates

    DEFF Research Database (Denmark)

    Barkholt, Pernille; Sanchez-Guajardo, Vanesa Maria; Kirik, Denis

    2012-01-01

    We have previously shown that persistent ﰇ-sy- nuclein overexpression in ventral midbrain of marmoset leads to a distinctive neurodegenerative process and motor defects. The neurodegeneration was confined to caudate putamen dopaminergic fibers in animals overexpressing wild-type (wt) ﰇ-synuclein....

  6. Combined gene overexpression of neuropeptide Y and its receptor Y5 in the hippocampus suppresses seizures

    DEFF Research Database (Denmark)

    Gøtzsche, Casper René; Nikitidou, Litsa; Sørensen, Andreas Toft

    2012-01-01

    We recently demonstrated that recombinant adeno-associated viral vector-induced hippocampal overexpression of neuropeptide Y receptor, Y2, exerts a seizure-suppressant effect in kindling and kainate-induced models of epilepsy in rats. Interestingly, additional overexpression of neuropeptide Y...

  7. Delayed habituation in Behcet's disease.

    Science.gov (United States)

    Gulturk, Sefa; Akyol, Melih; Kececi, Hulusi; Ozcelik, Sedat; Cinar, Ziynet; Demirkazik, Ayse

    2008-01-01

    The autonomic nervous system in Behcet's patients may be affected due to various reasons. This entity may be detected with the measurement of the electrodermal activities, heart rate variability and pupillometric methods. Habituation is one of the implicit forms of learning and memory and the loss of habituation can reveal pathological changes in the synaptic regions. To determine whether there is a functional decrease in the synaptic effectiveness (habituation) of the pathways to sympathetic neurons that had been repeatedly activated in Behcet's. Twelve patients with Behcet's disease and 12 healthy controls were included in the study. Sympathetic skin potential (SSP) records were taken at normal room temperature in a quiet place within a Faraday cage. Sixteen square wave single shock impulses (duration: 1200 ms, strength: 5 mA) were applied on each case. After the 1st stimulus, the SSP amplitudes were lower in the patients compared to the controls (P0.05). Whereas there was no significant differences among the SSP amplitudes after the 9th impulse in the controls (P>0.05). The habituation rate of the SSP after consecutive impulses was slowest in the patients compared to controls (P<0.001, t value=12.39). There is a delayed habituation in Behcet's disease and that may due to pathologic changes with vasculitis through their peripheral nerves.

  8. MAL Overexpression Leads to Disturbed Expression of Genes That Influence Cytoskeletal Organization and Differentiation of Schwann Cells

    Directory of Open Access Journals (Sweden)

    Daniela Schmid

    2014-09-01

    Full Text Available In the developing peripheral nervous system, a coordinated reciprocal signaling between Schwann cells and axons is crucial for accurate myelination. The myelin and lymphocyte protein MAL is a component of lipid rafts that is important for targeting proteins and lipids to distinct domains. MAL overexpression impedes peripheral myelinogenesis, which is evident by a delayed onset of myelination and reduced expression of the myelin protein zero (Mpz/P0 and the low-affinity neurotrophin receptor p75NTR . This study shows that MAL overexpression leads to a significant reduction of Mpz and p75NTR expression in primary mouse Schwann cell cultures, which was already evident before differentiation, implicating an effect of MAL in early Schwann cell development. Their transcription was robustly reduced, despite normal expression of essential transcription factors and receptors. Further, the cAMP response element-binding protein (CREB and phosphoinositide 3-kinase signaling pathways important for Schwann cell differentiation were correctly induced, highlighting that other so far unknown rate limiting factors do exist. We identified novel genes expressed by Schwann cells in a MAL-dependent manner in vivo and in vitro. A number of those, including S100a4, RhoU and Krt23, are implicated in cytoskeletal organization and plasma membrane dynamics. We showed that S100a4 is predominantly expressed by nonmyelinating Schwann cells, whereas RhoU was localized within myelin membranes, and Krt23 was detected in nonmyelinating as well as in myelinating Schwann cells. Their differential expression during early peripheral nerve development further underlines their possible role in influencing Schwann cell differentiation and myelination.

  9. Oncoprotein MDM2 Overexpression is Associated with Poor Prognosis in Distinct Non-Hodgkin's Lymphoma Entities

    DEFF Research Database (Denmark)

    Møller, Michael Boe; Nielsen, O; Pedersen, Niels Tinggaard

    1999-01-01

    MDM2 is an oncoprotein involved in the regulation of p53. MDM2 exerts its tumorigenic potential through p53-dependent and -independent mechanisms. It is frequently overexpressed in various malignancies. Little is known about the prognostic value of MDM2 expression in non-Hodgkin's lymphomas (NHL...... overexpression was present in 42 (22%) of 188 cases. The frequency was highest in aggressive/very aggressive NHL (P lymphomas, MDM2 overexpression was associated with higher-grade disease (P = .008). MDM2 overexpression was not related to a phenotype indicating...... altered p53. In univariate analysis MDM2 overexpression associated with short survival in follicle center lymphomas (P = .0256), extranodal marginal zone lymphomas (P lymphomas (P = .0047). The relation to poor prognosis was maintained in a Cox regression analysis including known...

  10. WDR62 overexpression is associated with a poor prognosis in patients with lung adenocarcinoma.

    Science.gov (United States)

    Shinmura, Kazuya; Kato, Hisami; Kawanishi, Yuichi; Igarashi, Hisaki; Inoue, Yusuke; Yoshimura, Katsuhiro; Nakamura, Satoki; Fujita, Hidehiko; Funai, Kazuhito; Tanahashi, Masayuki; Niwa, Hiroshi; Ogawa, Hiroshi; Sugimura, Haruhiko

    2017-08-01

    Human WDR62, which is localized in the cytoplasm including the centrosome, is known to be responsible for primary microcephaly; however, the role of WDR62 abnormality in cancers remains largely unknown. In this study, we aimed to reveal the pathological role of WDR62 abnormality in lung adenocarcinoma (LAC). We first examined the WDR62 mRNA expression level of LAC (n = 64) using a QRT-PCR analysis and found that WDR62 mRNA transcripts were significantly overexpressed in LAC (P = 0.0432, Wilcoxon matched pairs test). An immunohistochemical analysis for LAC (n = 237) showed that WDR62 proteins were also significantly overexpressed in LAC (P overexpression have a short overall survival (P = 0.0378, log-rank test), and a multivariate analysis revealed that WDR62 overexpression was an independent predictor of a poor survival outcome among LAC patients (hazard ratio, 2.032; 95% confidence interval, 1.071-3.777; P = 0.0305). Next, we examined the functional effect of WDR62 overexpression on the lung cancer cell line H1299. WDR62-overexpressing lung cancer cells exhibited an increase in cell growth. Moreover, the concurrent overexpression of WDR62 and TPX2, a WDR62-interacting protein that is also overexpressed in LAC, induced centrosome amplification in the lung cells. Finally, we disclosed that the concurrent overexpression of WDR62 and TPX2 is common in diverse human cancers, using data from the Cancer Genome Atlas. These results suggested that WDR62 overexpression is associated with a poor prognosis in patients with LAC and leads to an increase in the malignant potential of lung cells. © 2017 Wiley Periodicals, Inc.

  11. Time delays, population, and economic development

    Science.gov (United States)

    Gori, Luca; Guerrini, Luca; Sodini, Mauro

    2018-05-01

    This research develops an augmented Solow model with population dynamics and time delays. The model produces either a single stationary state or multiple stationary states (able to characterise different development regimes). The existence of time delays may cause persistent fluctuations in both economic and demographic variables. In addition, the work identifies in a simple way the reasons why economics affects demographics and vice versa.

  12. On Delay and Security in Network Coding

    Science.gov (United States)

    Dikaliotis, Theodoros K.

    2013-01-01

    In this thesis, delay and security issues in network coding are considered. First, we study the delay incurred in the transmission of a fixed number of packets through acyclic networks comprised of erasure links. The two transmission schemes studied are routing with hop-by-hop retransmissions, where every node in the network simply stores and…

  13. Delaying Developmental Mathematics: The Characteristics and Costs

    Science.gov (United States)

    Johnson, Marianne; Kuennen, Eric

    2004-01-01

    This paper investigates which students delay taking a required developmental mathematics course and the impact of delay on student performance in introductory microeconomics. Analysis of a sample of 1462 students at a large Midwestern university revealed that, although developmental-level mathematics students did not reach the same level of…

  14. ANALYSING SURFACE MOVEMENT DELAYS IN AN AIRPORT

    Directory of Open Access Journals (Sweden)

    Volodymyr Kharchenko

    2014-07-01

    Full Text Available Queuing effect can be in the different components of ground operations. Causes of surface – movement delays are long taxi – in and taxi – out operations during departure and arrival of aircraft. Surface movement delays in an airport are analyzed

  15. Analyzing delay causes in Egyptian construction projects

    Directory of Open Access Journals (Sweden)

    Mohamed M. Marzouk

    2014-01-01

    Full Text Available Construction delays are common problems in civil engineering projects in Egypt. These problems occur frequently during project life-time leading to disputes and litigation. Therefore, it is essential to study and analyze causes of construction delays. This research presents a list of construction delay causes retrieved from literature. The feedback of construction experts was obtained through interviews. Subsequently, a questionnaire survey was prepared. The questionnaire survey was distributed to thirty-three construction experts who represent owners, consultants, and contractor’s organizations. Frequency Index, Severity Index, and Importance Index are calculated and according to the highest values of them the top ten delay causes of construction projects in Egypt are determined. A case study is analyzed and compared to the most important delay causes in the research. Statistical analysis is carried out using analysis of variance ANOVA method to test delay causes, obtained from the survey. The test results reveal good correlation between groups while there is significant difference between them for some delay causes and finally roadmap for prioritizing delay causes groups is presented.

  16. Algebraic entropy for differential-delay equations

    OpenAIRE

    Viallet, Claude M.

    2014-01-01

    We extend the definition of algebraic entropy to a class of differential-delay equations. The vanishing of the entropy, as a structural property of an equation, signals its integrability. We suggest a simple way to produce differential-delay equations with vanishing entropy from known integrable differential-difference equations.

  17. A Polynomial Estimate of Railway Line Delay

    DEFF Research Database (Denmark)

    Cerreto, Fabrizio; Harrod, Steven; Nielsen, Otto Anker

    2017-01-01

    Railway service may be measured by the aggregate delay over a time horizon or due to an event. Timetables for railway service may dampen aggregate delay by addition of additional process time, either supplement time or buffer time. The evaluation of these variables has previously been performed...

  18. Test Anxiety and Academic Delay of Gratification

    Science.gov (United States)

    Bembenutty, Hefer

    2009-01-01

    The present study examined the relationship between college students' willingness to delay gratification, motivation, self-regulation of learning, and their level of test anxiety (N = 364). Academic delay of gratification refers to students' postponement of immediately available opportunities to satisfy impulses in favor of pursuing academic…

  19. Delaying gratification depends on social trust

    Science.gov (United States)

    Michaelson, Laura; de la Vega, Alejandro; Chatham, Christopher H.; Munakata, Yuko

    2013-01-01

    Delaying gratification is hard, yet predictive of important life outcomes, such as academic achievement and physical health. Prominent theories focus on the role of self-control, hypersensitivity to immediate rewards, and the cost of time spent waiting. However, delaying gratification may also require trust in people delivering future rewards as promised. To test the role of social trust, participants were presented with character vignettes and faces that varied in trustworthiness, and then choose between hypothetical smaller immediate or larger delayed rewards from those characters. Across two experiments, participants were less willing to wait for delayed rewards from less trustworthy characters, and perceived trustworthiness predicted willingness to delay gratification. These findings provide the first demonstration of a causal role for social trust in willingness to delay gratification, independent of other relevant factors, such as self-control or reward history. Thus, delaying gratification requires choosing not only a later reward, but a reward that is potentially less likely to be delivered, when there is doubt about the person promising it. Implications of this work include the need to revise prominent theories of delay of gratification, and new directions for interventions with populations characterized by impulsivity. PMID:23801977

  20. Delaying gratification depends on social trust

    Directory of Open Access Journals (Sweden)

    Laura eMichaelson

    2013-06-01

    Full Text Available Delaying gratification is hard, yet predictive of important life outcomes, such as academic achievement and physical health. Prominent theories focus on the role of self-control, hypersensitivity to immediate rewards, and the cost of time spent waiting. However, delaying gratification may also require trust in people delivering future rewards as promised. To test the role of social trust, participants were presented with character vignettes and faces that varied in trustworthiness, and then chose between hypothetical smaller immediate or larger delayed rewards from those characters. Across two experiments, participants were less willing to wait for delayed rewards from less trustworthy characters, and perceived trustworthiness predicted willingness to delay gratification. These findings provide the first demonstration of a causal role for social trust in willingness to delay gratification, independent of other relevant factors, such as self-control or reward history. Thus, delaying gratification requires choosing not only a later reward, but a reward that is potentially less likely to be delivered, when there is doubt about the person promising it. Implications of this work include the need to revise prominent theories of delay of gratification, and new directions for interventions with populations characterized by impulsivity.

  1. Beta delayed particle emission in light nuclei

    International Nuclear Information System (INIS)

    Riisager, K.; Gabelmann, H.

    1991-01-01

    A short discussion of theoretical treatments of beta delayed particle emission is followed by a presentation of data on the newly found beta delayed deuteron decay of 6 He. This decay cannot be described properly with existing theories. (author) 8 refs.; 3 figs

  2. Allee effects on population dynamics with delay

    International Nuclear Information System (INIS)

    Celik, C.; Merdan, H.; Duman, O.; Akin, O.

    2008-01-01

    In this paper, we study the stability analysis of equilibrium points of population dynamics with delay when the Allee effect occurs at low population density. Mainly, our mathematical results and numerical simulations point to the stabilizing effect of the Allee effects on population dynamics with delay

  3. Nonlinear delay monopoly with bounded rationality

    International Nuclear Information System (INIS)

    Matsumoto, Akio; Szidarovszky, Ferenc

    2012-01-01

    The purpose of this paper is to study the dynamics of a monopolistic firm in a continuous-time framework. The firm is assumed to be boundedly rational and to experience time delays in obtaining and implementing information on output. The dynamic adjustment process is based on the gradient of the expected profit. The paper is divided into three parts: we examine delay effects on dynamics caused by one-time delay and two-time delays in the first two parts. Global dynamics and analytical results on local dynamics are numerically confirmed in the third part. Four main results are demonstrated. First, the stability switch from stability to instability occurs only once in the case of a single delay. Second, the alternation of stability and instability can continue if two time delays are involved. Third, the occurence of Hopf bifurcation is analytically shown if stability is lost. Finally, in a bifurcation process, there are a period-doubling cascade to chaos and a period-halving cascade to the equilibrium point in the case of two time delays if the difference between the two delays is large.

  4. Striatal pre-enkephalin overexpression improves Huntington's disease symptoms in the R6/2 mouse model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Stéphanie Bissonnette

    Full Text Available The reduction of pre-enkephalin (pENK mRNA expression might be an early sign of striatal neuronal dysfunction in Huntington's disease (HD, due to mutated huntingtin protein. Indeed, striatopallidal (pENK-containing neurodegeneration occurs at earlier stage of the disease, compare to the loss of striatonigral neurons. However, no data are available about the functional role of striatal pENK in HD. According to the neuroprotective properties of opioids that have been recognized recently, the objective of this study was to investigate whether striatal overexpression of pENK at early stage of HD can improve motor dysfunction, and/or reduce striatal neuronal loss in the R6/2 transgenic mouse model of HD. To achieve this goal recombinant adeno-associated-virus (rAAV2-containing green fluorescence protein (GFP-pENK was injected bilaterally in the striatum of R6/2 mice at 5 weeks old to overexpress opioid peptide pENK. Striatal injection of rAAV2-GFP was used as a control. Different behavioral tests were carried out before and/or after striatal injections of rAAV2. The animals were euthanized at 10 weeks old. Our results demonstrate that striatal overexpression of pENK had beneficial effects on behavioral symptoms of HD in R6/2 by: delaying the onset of decline in muscular force; reduction of clasping; improvement of fast motor activity, short-term memory and recognition; as well as normalization of anxiety-like behavior. The improvement of behavioral dysfunction in R6/2 mice having received rAAV2-GFP-pENK associated with upregulation of striatal pENK mRNA; the increased level of enkephalin peptide in the striatum, globus pallidus and substantia nigra; as well as the slight increase in the number of striatal neurons compared with other groups of R6/2. Accordingly, we suggest that at early stage of HD upregulation of striatal enkephalin might play a key role at attenuating illness symptoms.

  5. Fuzzy delay model based fault simulator for crosstalk delay fault test ...

    Indian Academy of Sciences (India)

    In this paper, a fuzzy delay model based crosstalk delay fault simulator is proposed. As design .... To find the quality of non-robust tests, a fuzzy delay ..... Dubois D and Prade H 1989 Processing Fuzzy temporal knowledge. IEEE Transactions ...

  6. Delay-dependent exponential stability of cellular neural networks with time-varying delays

    International Nuclear Information System (INIS)

    Zhang Qiang; Wei Xiaopeng; Xu Jin

    2005-01-01

    The global exponential stability of cellular neural networks (CNNs) with time-varying delays is analyzed. Two new sufficient conditions ensuring global exponential stability for delayed CNNs are obtained. The conditions presented here are related to the size of delay. The stability results improve the earlier publications. Two examples are given to demonstrate the effectiveness of the obtained results

  7. Synchronization of delayed systems in the presence of delay time modulation

    International Nuclear Information System (INIS)

    Kye, Won-Ho; Choi, Muhan; Kim, Myung-Woon; Lee, Soo-Young; Rim, Sunghwan; Kim, Chil-Min; Park, Young-Jai

    2004-01-01

    We investigate synchronization in the presence of delay time modulation for application to communication. We have observed that the robust synchronization is established by a common delay signal and its threshold is presented using Lyapunov exponents analysis. The influence of the delay time modulation in chaotic oscillators is also discussed

  8. Overexpression of mouse TTF-2 gene causes cleft palate

    Science.gov (United States)

    Meng, Tian; Shi, Jia-Yu; Wu, Min; Wang, Yan; Li, Ling; Liu, Yan; Zheng, Qian; Huang, Lei; Shi, Bing

    2012-01-01

    In humans, mutations of the gene encoding for thyroid transcription factor-2 (TTF-2 or FOXE1) result in Bamforth syndrome. Bamforth syndrome is characterized by agenesis, cleft palate, spiky hair and choanal atresia. TTF-2 null mice (TTF-2−/−) also exhibit cleft palate, suggesting its involvement in the palatogenesis. However, the molecular pathology and genetic regulation by TTF2 remain largely unknown. In the present study, the recombinant expression vector pBROAD3-TTF-2 containing the promoter of the mouse ROSA26 gene was created to form the structural gene of mouse TTF-2 and was microinjected into the male pronuclei of fertilized ova. Sequence analysis confirmed that the TTF-2 transgenic mouse model was established successfully. The transgenic mice displayed a phenotype of cleft palate. In addition, we found that TTF-2 was highly expressed in the medial edge epithelium (MEE) from the embryonic day 12.5 (E12.5) to E14.5 in TTF-2 transgenic mice. These observations suggest that overexpression of TTF-2 during palatogenesis may contribute to formation of cleft palate. PMID:22304410

  9. Cardiac muscarinic receptor overexpression in sudden infant death syndrome.

    Directory of Open Access Journals (Sweden)

    Angelo Livolsi

    Full Text Available BACKGROUND: Sudden infant death syndrome (SIDS remains the leading cause of death among infants less than 1 year of age. Disturbed expression of some neurotransmitters and their receptors has been shown in the central nervous system of SIDS victims but no biological abnormality of the peripheral vago-cardiac system has been demonstrated to date. The present study aimed to seek vago-cardiac abnormalities in SIDS victims. The cardiac level of expression of muscarinic receptors, as well as acetylcholinesterase enzyme activity were investigated. METHODOLOGY/PRINCIPAL FINDINGS: Left ventricular samples and blood samples were obtained from autopsies of SIDS and children deceased from non cardiac causes. Binding experiments performed with [(3H]NMS, a selective muscarinic ligand, in cardiac membrane preparations showed that the density of cardiac muscarinic receptors was increased as shown by a more than doubled B(max value in SIDS (n = 9 SIDS versus 8 controls. On average, the erythrocyte acetylcholinesterase enzyme activity was also significantly increased (n = 9 SIDS versus 11 controls. CONCLUSIONS: In the present study, it has been shown for the first time that cardiac muscarinic receptor overexpression is associated with SIDS. The increase of acetylcholinesterase enzyme activity appears as a possible regulatory mechanism.

  10. GNB3 overexpression causes obesity and metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Alev Cagla Ozdemir

    Full Text Available The G-protein beta subunit 3 (GNB3 gene has been implicated in obesity risk; however, the molecular mechanism of GNB3-related disease is unknown. GNB3 duplication is responsible for a syndromic form of childhood obesity, and an activating DNA sequence variant (C825T in GNB3 is also associated with obesity. To test the hypothesis that GNB3 overexpression causes obesity, we created bacterial artificial chromosome (BAC transgenic mice that carry an extra copy of the human GNB3 risk allele. Here we show that GNB3-T/+ mice have increased adiposity, but not greater food intake or a defect in satiety. GNB3-T/+ mice have elevated fasting plasma glucose, insulin, and C-peptide, as well as glucose intolerance, indicating type 2 diabetes. Fasting plasma leptin, triglycerides, cholesterol and phospholipids are elevated, suggesting metabolic syndrome. Based on a battery of behavioral tests, GNB3-T/+ mice did not exhibit anxiety- or depressive-like phenotypes. GNB3-T/+ and wild-type animals have similar activity levels and heat production; however, GNB3-T/+ mice exhibit dysregulation of acute thermogenesis. Finally, Ucp1 expression is significantly lower in white adipose tissue (WAT in GNB3-T/+ mice, suggestive of WAT remodeling that could lead to impaired cellular thermogenesis. Taken together, our study provides the first functional link between GNB3 and obesity, and presents insight into novel pathways that could be applied to combat obesity and type 2 diabetes.

  11. GNB3 overexpression causes obesity and metabolic syndrome.

    Science.gov (United States)

    Ozdemir, Alev Cagla; Wynn, Grace M; Vester, Aimee; Weitzmann, M Neale; Neigh, Gretchen N; Srinivasan, Shanthi; Rudd, M Katharine

    2017-01-01

    The G-protein beta subunit 3 (GNB3) gene has been implicated in obesity risk; however, the molecular mechanism of GNB3-related disease is unknown. GNB3 duplication is responsible for a syndromic form of childhood obesity, and an activating DNA sequence variant (C825T) in GNB3 is also associated with obesity. To test the hypothesis that GNB3 overexpression causes obesity, we created bacterial artificial chromosome (BAC) transgenic mice that carry an extra copy of the human GNB3 risk allele. Here we show that GNB3-T/+ mice have increased adiposity, but not greater food intake or a defect in satiety. GNB3-T/+ mice have elevated fasting plasma glucose, insulin, and C-peptide, as well as glucose intolerance, indicating type 2 diabetes. Fasting plasma leptin, triglycerides, cholesterol and phospholipids are elevated, suggesting metabolic syndrome. Based on a battery of behavioral tests, GNB3-T/+ mice did not exhibit anxiety- or depressive-like phenotypes. GNB3-T/+ and wild-type animals have similar activity levels and heat production; however, GNB3-T/+ mice exhibit dysregulation of acute thermogenesis. Finally, Ucp1 expression is significantly lower in white adipose tissue (WAT) in GNB3-T/+ mice, suggestive of WAT remodeling that could lead to impaired cellular thermogenesis. Taken together, our study provides the first functional link between GNB3 and obesity, and presents insight into novel pathways that could be applied to combat obesity and type 2 diabetes.

  12. Overexpression of SOS genes in ciprofloxacin resistant Escherichia coli mutants.

    Science.gov (United States)

    Pourahmad Jaktaji, Razieh; Pasand, Shirin

    2016-01-15

    Fluoroquinolones are important antibiotics for the treatment of urinary tract infections caused by Escherichia coli. Mutational studies have shown that ciprofloxacin, a member of fluoroquinolones induces SOS response and mutagenesis in pathogenic bacteria which in turn develop antibiotic resistance. However, inhibition of SOS response can increase recombination activity which in turn leads to genetic variation. The aim of this study was to measure 5 SOS genes expressions in nine E. coli mutants with different MICs for ciprofloxacin following exposure to ciprofloxacin. Gene expression was assessed by quantitative real time PCR. Gene alteration assessment was conducted by PCR amplification and DNA sequencing. Results showed that the expression of recA was increased in 5 mutants. This overexpression is not related to gene alteration, and enhances the expression of polB and umuCD genes encoding nonmutagenic and mutagenic polymerases, respectively. The direct relationship between the level of SOS expression and the level of resistance to ciprofloxacin was also indicated. It was concluded that novel therapeutic strategy that inhibits RecA activity would enhance the efficiency of common antibiotics against pathogenic bacteria. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Overexpression of Human Bone Alkaline Phosphatase in Pichia Pastoris

    Science.gov (United States)

    Karr, Laurel; Malone, Christine, C.; Rose, M. Franklin (Technical Monitor)

    2000-01-01

    The Pichiapastoris expression system was utilized to produce functionally active human bone alkaline phosphatase in gram quantities. Bone alkaline phosphatase is a key enzyme in bone formation and biomineralization, yet important questions about its structural chemistry and interactions with other cellular enzymes in mineralizing tissues remain unanswered. A soluble form of human bone alkaline phosphatase was constructed by deletion of the 25 amino acid hydrophobic C-terminal region of the encoding cDNA and inserted into the X-33 Pichiapastoris strain. An overexpression system was developed in shake flasks and converted to large-scale fermentation. Alkaline phosphatase was secreted into the medium to a level of 32mgAL when cultured in shake flasks. Enzyme activity was 12U/mg measured by a spectrophotometric assay. Fermentation yielded 880mgAL with enzymatic activity of 968U/mg. Gel electrophoresis analysis indicates that greater than 50% of the total protein in the fermentation is alkaline phosphatase. A purification scheme has been developed using ammonium sulfate precipitation followed by hydrophobic interaction chromatography. We are currently screening crystallization conditions of the purified recombinant protein for subsequent X-ray diffraction analyses. Structural data should provide additional information on the role of alkaline phosphatase in normal bone mineralization and in certain bone mineralization anomalies.

  14. Overexpression of chitinase like protein YKL-40 in leukemia patients

    Directory of Open Access Journals (Sweden)

    Anil K. Hurmale

    2013-01-01

    Full Text Available YKL-40 is a member of mammalian chitanase (CHI3L1, expressed and secreted by several types of solid tumor cells, inflammatory cells and stem cells. The precise physiological role of YKL-40 in cancer is still not clear and it is suggested that it play a role in cancer cell proliferation, differentiation, metastatic potential, cell attachment and migration, reorganization and tissue remodeling.The aim of the study was to check the appearance of YKL-40 in leukemic cells and over-expression of YKL-40 in the plasma of leukemia patients in comparison to healthy controls, and find whether YKL-40 could serve as a peripheral biomarker for leukemia. The study was conducted between July 2012 and March 2013 and included 67 volunteers, 55 having leukemia at the stage of diagnosis ofthe disease and 12 normal healthy volunteers. YKL-40 levels were determined in all plasma samples using the YKL-40 enzyme-linked immunosorbent assay (ELISA kit and expression of YKL-40 was observed by using immunocytochemical (ICC analysis. YKL-40 plasma levels differed significantly between patients with leukemia and the normal healthy volunteers (P=<0.001 and YKL-40 was positively expressed in all four types of leukemia (AML, ALL, CLL and CML specimens.

  15. Caveolin-1 overexpression in benign and malignant salivary gland tumors.

    Science.gov (United States)

    Jaafari-Ashkavandi, Zohreh; Ashraf, Mohammad Javad; Nazhvani, Ali Dehghani; Azizi, Zahra

    2016-02-01

    Caveolin-1, a tyrosine-phosphorylated protein, is supposed to have different regulatory roles as promoter or suppressor in many human cancers. However, no published study concerned its expression in benign and malignant salivary gland tumors. The aim of this study was to evaluate and compare the expression of Cav-1 in the most common benign and malignant salivary gland tumors and evaluate its correlation with proliferation activity. In this cross-sectional retrospective study, immunohistochemical expression of caveolin-1 and Ki67 were evaluated in 49 samples, including 11 normal salivary glands, 15 cases of pleomorphic adenoma (PA), 13 adenoid cystic carcinomas (AdCC), and 10 mucoepidermoid carcinomas (MEC). The expression of Cav-1 was seen in 18 % of normal salivary glands and 85 % of tumors. The immunoreaction in the tumors was significantly higher than normal tissues (P = 0.001), but the difference between benign and malignant tumors was not significant (P = 0.07). Expression of Cav-1 was correlated with Ki67 labeling index in PAs, but not in malignant tumors. Cav-1 expression was not in association with tumor size and stage. Overexpression of Cav-1 was found in salivary gland tumors in comparison with normal tissues, but no significant difference was observed between benign and malignant tumors. Cav-1 was inversely correlated with proliferation in PA. Therefore, this marker may participate in tumorigenesis of salivary gland tumors and may be a potential biomarker for cancer treatments.

  16. Clinical significance of Phosphatidyl Inositol Synthase overexpression in oral cancer

    International Nuclear Information System (INIS)

    Kaur, Jatinder; Sawhney, Meenakshi; DattaGupta, Siddartha; Shukla, Nootan K; Srivastava, Anurag; Ralhan, Ranju

    2010-01-01

    We reported increased levels of Phosphatidyl Inositol synthase (PI synthase), (enzyme that catalyses phosphatidyl inositol (PI) synthesis-implicated in intracellular signaling and regulation of cell growth) in smokeless tobacco (ST) exposed oral cell cultures by differential display. This study determined the clinical significance of PI synthase overexpression in oral squamous cell carcinoma (OSCC) and premalignant lesions (leukoplakia), and identified the downstream signaling proteins in PI synthase pathway that are perturbed by smokeless tobacco (ST) exposure. Tissue microarray (TMA) Immunohistochemistry, Western blotting, Confocal laser scan microscopy, RT-PCR were performed to define the expression of PI synthase in clinical samples and in oral cell culture systems. Significant increase in PI synthase immunoreactivity was observed in premalignant lesions and OSCCs as compared to oral normal tissues (p = 0.000). Further, PI synthase expression was significantly associated with de-differentiation of OSCCs, (p = 0.005) and tobacco consumption (p = 0.03, OR = 9.0). Exposure of oral cell systems to smokeless tobacco (ST) in vitro confirmed increase in PI synthase, Phosphatidylinositol 3-kinase (PI3K) and cyclin D1 levels. Collectively, increased PI synthase expression was found to be an early event in oral cancer and a target for smokeless tobacco

  17. Impaired baroreflex function in mice overexpressing alpha-synuclein

    Directory of Open Access Journals (Sweden)

    Sheila eFleming

    2013-07-01

    Full Text Available Cardiovascular autonomic dysfunction, such as orthostatic hypotension consequent to baroreflex failure and cardiac sympathetic denervation, is frequently observed in the synucleinopathy Parkinson’s disease (PD. In the present study, the baroreceptor reflex was assessed in mice overexpressing human wildtype alpha-synuclein (Thy1-aSyn, a genetic mouse model of synucleinopathy. The beat-to-beat change in heart rate, computed from R-R interval, in relation to blood pressure was measured in anesthetized and conscious mice equipped with arterial blood pressure telemetry transducers during transient bouts of hypertension and hypotension. Compared to wildtype, tachycardia following nitroprusside-induced hypotension was significantly reduced in Thy1-aSyn mice. Thy1-aSyn mice also showed an abnormal cardiovascular response (i.e., diminished tachycardia to muscarinic blockade with atropine. We conclude that Thy1-aSyn mice have impaired basal and dynamic range of sympathetic and parasympathetic-mediated changes in heart rate and will be a useful model for long-term study of cardiovascular autonomic dysfunction associated with PD.

  18. Gravitational Lens Time Delays Using Polarization Monitoring

    Directory of Open Access Journals (Sweden)

    Andrew Biggs

    2017-11-01

    Full Text Available Gravitational lens time delays provide a means of measuring the expansion of the Universe at high redshift (and therefore in the ‘Hubble flow’ that is independent of local calibrations. It was hoped that many of the radio lenses found in the JVAS/CLASS survey would yield time delays as these were selected to have flat spectra and are dominated by multiple compact components. However, despite extensive monitoring with the Very Large Array (VLA, time delays have only been measured for three of these systems (out of 22. We have begun a programme to reanalyse the existing VLA monitoring data with the goal of producing light curves in polarized flux and polarization position angle, either to improve delay measurements or to find delays for new sources. Here, we present preliminary results on the lens system B1600+434 which demonstrate the presence of correlated and substantial polarization variability in each image.

  19. Controllability of nonlinear delay oscillating systems

    Directory of Open Access Journals (Sweden)

    Chengbin Liang

    2017-05-01

    Full Text Available In this paper, we study the controllability of a system governed by second order delay differential equations. We introduce a delay Gramian matrix involving the delayed matrix sine, which is used to establish sufficient and necessary conditions of controllability for the linear problem. In addition, we also construct a specific control function for controllability. For the nonlinear problem, we construct a control function and transfer the controllability problem to a fixed point problem for a suitable operator. We give a sufficient condition to guarantee the nonlinear delay system is controllable. Two examples are given to illustrate our theoretical results by calculating a specific control function and inverse of a delay Gramian matrix.

  20. Dynamics of microbubble oscillators with delay coupling

    Science.gov (United States)

    Heckman, C. R.; Sah, S. M.; Rand, R. H.

    2010-10-01

    We investigate the stability of the in-phase mode in a system of two delay-coupled bubble oscillators. The bubble oscillator model is based on a 1956 paper by Keller and Kolodner. Delay coupling is due to the time it takes for a signal to travel from one bubble to another through the liquid medium that surrounds them. Using techniques from the theory of differential-delay equations as well as perturbation theory, we show that the equilibrium of the in-phase mode can be made unstable if the delay is long enough and if the coupling strength is large enough, resulting in a Hopf bifurcation. We then employ Lindstedt's method to compute the amplitude of the limit cycle as a function of the time delay. This work is motivated by medical applications involving noninvasive localized drug delivery via microbubbles.

  1. Overexpression of pucC improves the heterologous protein expression level in a Rhodobacter sphaeroides expression system.

    Science.gov (United States)

    Cheng, L; Chen, G; Ding, G; Zhao, Z; Dong, T; Hu, Z

    2015-04-27

    The Rhodobacter sphaeroides system has been used to express membrane proteins. However, its low yield has substantially limited its application. In order to promote the protein expression capability of this system, the pucC gene, which plays a crucial role in assembling the R. sphaeroides light-harvesting 2 complex (LH2), was overexpressed. To build a pucC overexpression strain, a pucC overexpression vector was constructed and transformed into R. sphaeroides CQU68. The overexpression efficiency was evaluated by quantitative real-time polymerase chain reaction. A well-used reporter β-glucuronidase (GUS) was fusion-expressed with LH2 to evaluate the heterologous protein expression level. As a result, the cell culture and protein in the pucC overexpression strain showed much higher typical spectral absorption peaks at 800 and 850 nm compared with the non-overexpression strain, suggesting a higher expression level of LH2-GUS fusion protein in the pucC overexpression strain. This result was further confirmed by Western blot, which also showed a much higher level of heterologous protein expression in the pucC overexpression strain. We further compared GUS activity in pucC overexpression and non-overexpression strains, the results of which showed that GUS activity in the pucC overexpression strain was approximately ten-fold that in the non-overexpression strain. These results demonstrate that overexpressed pucC can promote heterologous protein expression levels in R. sphaeroides.

  2. Microscopic Control Delay Modeling at Signalized Arterials Using Bluetooth Technology

    OpenAIRE

    Rajasekhar, Lakshmi

    2011-01-01

    Real-time control delay estimation is an important performance measure for any intersection to improve the signal timing plans dynamically in real-time and hence improve the overall system performance. Control delay estimates helps to determine the level-of-service (LOS) characteristics of various approaches at an intersection and takes into account deceleration delay, stopped delay and acceleration delay. All kinds of traffic delay calculation especially control delay calculation has always ...

  3. On the cost/delay tradeoff of wireless delay tolerant geographic routing

    OpenAIRE

    Tasiopoulos, Argyrios; Tsiaras, Christos; Toumpis, Stavros

    2012-01-01

    In Delay Tolerant Networks (DTNs), there is a fundamental tradeoff between the aggregate transport cost of a packet and the delay in its delivery. We study this tradeoff in the context of geographical routing in wireless DTNs.We ?rst specify the optimal cost/delay tradeoff, i.e., the tradeoff under optimal network operation, using a dynamic network construction termed the Cost/Delay Evolving Graph (C/DEG) and the Optimal Cost/Delay Curve (OC/DC), a function that gives the minimum possible agg...

  4. Reward acts as a signal to control delay-period activity in delayed-response tasks.

    Science.gov (United States)

    Ichihara-Takeda, Satoe; Takeda, Kazuyoshi; Funahashi, Shintaro

    2010-03-31

    Prefrontal delay-period activity represents a neural mechanism for the active maintenance of information and needs to be controlled by some signal to appropriately operate working memory. To examine whether reward-delivery acts as this signal, the effects of delay-period activity in response to unexpected reward-delivery were examined by analyzing single-neuron activity recorded in the primate dorsolateral prefrontal cortex. Among neurons that showed delay-period activity, 34% showed inhibition of this activity in response to unexpected reward-delivery. The delay-period activity of these neurons was affected by the expectation of reward-delivery. The strength of the reward signal in controlling the delay-period activity is related to the strength of the effect of reward information on the delay-period activity. These results indicate that reward-delivery acts as a signal to control delay-period activity.

  5. Chaos synchronization in time-delayed systems with parameter mismatches and variable delay times

    International Nuclear Information System (INIS)

    Shahverdiev, E.M.; Nuriev, R.A.; Hashimov, R.H.; Shore, K.A.

    2004-06-01

    We investigate synchronization between two undirectionally linearly coupled chaotic nonidentical time-delayed systems and show that parameter mismatches are of crucial importance to achieve synchronization. We establish that independent of the relation between the delay time in the coupled systems and the coupling delay time, only retarded synchronization with the coupling delay time is obtained. We show that with parameter mismatch or without it neither complete nor anticipating synchronization occurs. We derive existence and stability conditions for the retarded synchronization manifold. We demonstrate our approach using examples of the Ikeda and Mackey Glass models. Also for the first time we investigate chaos synchronization in time-delayed systems with variable delay time and find both existence and sufficient stability conditions for the retarded synchronization manifold with the coupling-delay lag time. (author)

  6. Overexpression of Insulin-like Growth Factor-1 Receptor Is Associated With Penile Cancer Progression.

    Science.gov (United States)

    Ball, Mark W; Bezerra, Stephania M; Chaux, Alcides; Faraj, Sheila F; Gonzalez-Roibon, Nilda; Munari, Enrico; Sharma, Rajni; Bivalacqua, Trinity J; Netto, George J; Burnett, Arthur L

    2016-06-01

    To evaluate insulin-like growth factor-1 receptor (IGF1R) expression in penile cancer and its association with oncologic outcomes. Tissue microarrays were constructed from 53 patients treated at our institution. Expression of IGF1R was evaluated using a Her2-like scoring system. Overexpression was defined as 1+ or greater membranous staining. Association of IGF1R expression with pathologic features was assessed with comparative statistics, and association with local recurrence, progression to nodal or distance metastases, or death was assessed with Kaplan-Meier survival analysis and Cox proportional hazard regression models. Overall, IGF1R overexpression was seen in 33 (62%) cases. With a median follow-up of 27.8 months, IGF1R overexpression was associated with inferior progression-free survival (PFS) (P  =  .003). In a multivariable model controlling for grade, T stage, perineural invasion, and lymphovascular invasion, IGF1R expression was independently associated with disease progression (hazard ratio 2.3, 95% confidence interval 1.1-5.1, P  =  .03. Comparing patients without IGF1R overexpression to those with overexpression, 5-year PFS was 94.1% vs 45.8%. IGF1R overexpression was associated with inferior PFS in penile cancer. Drugs that target IGF1R and downstream messengers may have a therapeutic benefit in patients that exhibit IGF1R overexpression. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. MET overexpression, gene amplification and relevant clinicopathological features in gastric adenocarcinoma.

    Science.gov (United States)

    Zhang, Jing; Guo, Lei; Liu, Xiuyun; Li, Wenbin; Ying, Jianming

    2017-02-07

    This study was conducted to investigate the expression of MET in Chinese gastric adenocarcinoma cohort, the correlation between MET overexpression and clinical pathological features, HER2 expression and MET gene amplification. A total of 816 gastric adenocarcinoma patients were included and MET and HER2 immunohistochemical (IHC) staining were performed. IHC and dual-color silver in situ hybridization analysis were performed in the tissue microarrays, constructed from the 240 patients who were randomly selected. MET overexpression (IHC 3+) was observed in 6.0% (49/816) of the cohort. MET overexpression rate was higher in patients with poor prognostic factors, such as clinical stages III/IV (p =0.012) and pathologic stages T3/T4 (p =0.027). The HER2 overexpression (IHC 3+) rate was 8.8% (72/816) and MET overexpression rate was higher in HER2 positive patients (9.7%, 7/72). A high concordance rate (94.6%) between MET overexpression and gene amplification was demonstrated. Therefore, MET overexpression could serve as a prognostic biomarker and a potential therapeutic target for gastric cancer.

  8. General applicability of synthetic gene-overexpression for cell-type ratio control via reprogramming.

    Science.gov (United States)

    Ishimatsu, Kana; Hata, Takashi; Mochizuki, Atsushi; Sekine, Ryoji; Yamamura, Masayuki; Kiga, Daisuke

    2014-09-19

    Control of the cell-type ratio in multistable systems requires wide-range control of the initial states of cells. Here, using a synthetic circuit in E. coli, we describe the use of a simple gene-overexpression system combined with a bistable toggle switch, for the purposes of enabling the wide-range control of cellular states and thus generating arbitrary cell-type ratios. Theoretically, overexpression induction temporarily alters the bistable system to a monostable system, in which the location of the single steady state of cells can be manipulated over a wide range by regulating the overexpression levels. This induced cellular state becomes the initial state of the basal bistable system upon overexpression cessation, which restores the original bistable system. We experimentally demonstrated that the overexpression induced a monomodal cell distribution, and subsequent overexpression withdrawal generated a bimodal distribution. Furthermore, as designed theoretically, regulating the overexpression levels by adjusting the concentrations of small molecules generated arbitrary cell-type ratios.

  9. Overexpression of decorin promoted angiogenesis in diabetic cardiomyopathy via IGF1R-AKT-VEGF signaling.

    Science.gov (United States)

    Lai, Jinsheng; Chen, Fuqiong; Chen, Jing; Ruan, Guoran; He, Mengying; Chen, Chen; Tang, Jiarong; Wang, Dao Wen

    2017-03-14

    Microcirculatory dysfunction is believed to play an important role in diabetic cardiomyopathy. The small leucine-rich proteoglycan decorin is generally considered a pro-angiogenic factor. Here, we investigate whether overexpression of decorin ameliorates diabetic cardiomyopathy and its effects on angiogenesis in vivo and in vitro. Diabetes was induced through intraperitoneal injection with streptozotocin combined with a high-fat diet, and decorin was overexpressed via recombinant adeno-associated virus in Wistar rats. Six months later, cardiac function was determined using an echocardiography and cardiac catheter system. The results showed that cardiac function was decreased in diabetic rats and restored by overexpression of decorin. In addition, overexpression of decorin upregulated the expression of VEGF and attenuated the reduction in the cardiac capillary density. In the in vitro study, high glucose induced apoptosis and inhibited the capabilities of tube formation, migration and proliferation, which were all ameliorated by decorin overexpression. Meanwhile, decorin overexpression increased the expression of VEGF and IGF1R, as well as the phosphorylation level of AKT and AP-1. Nonetheless, all of these effects were abolished by pretreatment with the IGF1R antibody or AKT inhibitor. In conclusion, overexpression of decorin ameliorated diabetic cardiomyopathy and promoted angiogenesis through the IGF1R-AKT-VEGF signaling pathway in vivo and in vitro.

  10. Overexpression of protein O-fucosyltransferase 1 accelerates hepatocellular carcinoma progression via the Notch signaling pathway

    International Nuclear Information System (INIS)

    Ma, Lijie; Dong, Pingping; Liu, Longzi; Gao, Qiang; Duan, Meng; Zhang, Si; Chen, She; Xue, Ruyi; Wang, Xiaoying

    2016-01-01

    Aberrant activation of Notch signaling frequently occurs in liver cancer, and is associated with liver malignancies. However, the mechanisms regulating pathologic Notch activation in hepatocellular carcinoma (HCC) remain unclear. Protein O-fucosyltransferase 1 (Pofut1) catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch. In the present study, we detected the expression of Pofut1 in 8 HCC cell lines and 253 human HCC tissues. We reported that Pofut1 was overexpressed in HCC cell lines and clinical HCC tissues, and Pofut1 overexpression clinically correlated with the unfavorable survival and high disease recurrence in HCC. The in vitro assay demonstrated that Pofut1 overexpression accelerated the cell proliferation and migration in HCC cells. Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofut1 overexpression could be a reason for the aberrant activation of Notch signaling in HCC. Taken together, our findings indicated that an aberrant activated Pofut1-Notch pathway was involved in HCC progression, and blockage of this pathway could be a promising strategy for the therapy of HCC. - Highlights: • Pofut1 overexpression in HCC was correlated with aggressive tumor behaviors. • Pofut1 overexpression in HCC was associated with poor prognosis. • Pofut1 promoted cell proliferation, migration and invasion in hepatoma cells. • Pofut1 activated Notch signaling pathway in hepatoma cells.

  11. Overexpression of protein O-fucosyltransferase 1 accelerates hepatocellular carcinoma progression via the Notch signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Lijie [Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai (China); Dong, Pingping [Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai (China); Liu, Longzi; Gao, Qiang; Duan, Meng [Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai (China); Zhang, Si; Chen, She [Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai (China); Xue, Ruyi, E-mail: xue.ruyi@zs-hospital.sh.cn [Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai (China); Wang, Xiaoying, E-mail: xiaoyingwang@fudan.edu.cn [Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai (China)

    2016-04-29

    Aberrant activation of Notch signaling frequently occurs in liver cancer, and is associated with liver malignancies. However, the mechanisms regulating pathologic Notch activation in hepatocellular carcinoma (HCC) remain unclear. Protein O-fucosyltransferase 1 (Pofut1) catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch. In the present study, we detected the expression of Pofut1 in 8 HCC cell lines and 253 human HCC tissues. We reported that Pofut1 was overexpressed in HCC cell lines and clinical HCC tissues, and Pofut1 overexpression clinically correlated with the unfavorable survival and high disease recurrence in HCC. The in vitro assay demonstrated that Pofut1 overexpression accelerated the cell proliferation and migration in HCC cells. Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofut1 overexpression could be a reason for the aberrant activation of Notch signaling in HCC. Taken together, our findings indicated that an aberrant activated Pofut1-Notch pathway was involved in HCC progression, and blockage of this pathway could be a promising strategy for the therapy of HCC. - Highlights: • Pofut1 overexpression in HCC was correlated with aggressive tumor behaviors. • Pofut1 overexpression in HCC was associated with poor prognosis. • Pofut1 promoted cell proliferation, migration and invasion in hepatoma cells. • Pofut1 activated Notch signaling pathway in hepatoma cells.

  12. Delays in Building Construction Projects in Ghana

    Directory of Open Access Journals (Sweden)

    Adwoa B Agyakwah-Baah

    2010-07-01

    Full Text Available This study investigates the causes of delay of building construction projects in Ghana to determine the most important according to the key project participants; clients, consultants, and contractors. Thirty-two possible causes of delay were identified from the literature and semi-structured interviews of 15 key players in the implementation process. These delay factors were further categorised into nine major groups. The list of delay causes was subjected to a questionnaire survey for the identification of the most important causes of delay. The field survey included 130 respondents made up of 39 contractors, 37 clients and 54 consultants. The relative importance of the individual causes and the groups were calculated and ranked by their relative importance index. The overall results of the study indicate that the respondents generally agree that financial group factors ranked highest among the major factors causing delay in construction projects in Ghana. The financial group factors were delay in honouring payment certificates, difficulty in accessing credit and fluctuation in prices. Materials group factors are second followed by scheduling and controlling factors.

  13. Behavioral effects of delayed timeouts from reinforcement.

    Science.gov (United States)

    Byrne, Tom; Poling, Alan

    2017-03-01

    Timeouts are sometimes used in applied settings to reduce target responses, and in some circumstances delays are unavoidably imposed between the onset of a timeout and the offset of the response that produces it. The present study examined the effects of signaled and unsignaled timeouts in rats exposed to concurrent fixed-ratio 1 fixed-ratio 1 schedules of food delivery, where each response on one lever, the location of which changed across conditions, produced both food and a delayed 10-s timeout. Delays of 0 to 38 s were examined. Delayed timeouts often, but not always, substantially reduced the number of responses emitted on the lever that produced timeouts relative to the number emitted on the lever that did not produce timeouts. In general, greater sensitivity was observed to delayed timeouts when they were signaled. These results demonstrate that delayed timeouts, like other delayed consequences, can affect behavior, albeit less strongly than immediate consequences. © 2017 Society for the Experimental Analysis of Behavior.

  14. ERBB-2 overexpression as a risk factor for malignant phaeochromocytomas and paraganglinomas.

    Science.gov (United States)

    Wang, Weiqing; Zhong, Xu; Ye, Lei; Qi, Yan; Su, TingWei; Wei, Qing; Xie, Jing; Jiang, Lei; Jiang, Yiran; Zhou, Weiwei; Cui, Bin; Ning, Guang

    2016-06-01

    There are currently no good histological or molecular markers to differentiate benign from malignant phaeochromocytomas and paraganglinomas (PPGLs). Our previous cross-sectional study observed that ERBB-2 overexpression was associated with malignant PPGLs. This study aimed to evaluate the predictive value of ERBB-2 overexpression for metastasis in PPGLs in a large population. A total of 262 patients diagnosed as PPGLs in our institution between 2002 and 2012 were included. We analysed ERBB-2 protein expression in the primary PPGL tumours by immunohistochemistry (IHC) and ERBB-2 amplification by fluorescence in situ hybridization (FISH). Direct Sanger sequencing was performed to examine ERBB-2 exon 20 mutations. The occurrence of malignant PPGLs was documented in the follow-up period. Kaplan-Meier analysis and Cox proportional hazard models were used to evaluate the association between ERBB-2 overexpression and metastasis of PPGLs. Twenty-six (9·9%) patients had ERBB-2 overexpression in their primary PPGL tumours, which was significantly associated with ERBB-2 amplification (17/25, 68%). No ERBB-2 mutation was found. At a median follow-up of 4·5 years, a total of 23 malignant PPGLs were documented, including eight (30·8%) patients in the ERBB-2 overexpression group and 15 (6·4%) patients in the ERBB-2-negative group. The incidence rate of metastasis was 5·3 per 100 person-years vs 1·4 per 100 person-years in the ERBB-2 overexpression and ERBB-2-negative groups (P overexpression was associated with decreased metastasis-free survival (P = 0·001, log-rank test). After adjusting for primary tumour size and location, Cox regression analysis revealed that ERBB-2 overexpression was independently associated with risk of malignant PPGLs (HR = 2·78; 95% CI, 1·12-6·90; P = 0·028). Patients harbouring tumours with ERBB-2 overexpression have a significantly higher risk of developing malignant PPGLs. © 2016 John Wiley & Sons Ltd.

  15. Overexpression of Oct4 suppresses the metastatic potential of breast cancer cells via Rnd1 downregulation.

    Science.gov (United States)

    Shen, Long; Qin, Kunhua; Wang, Dekun; Zhang, Yan; Bai, Nan; Yang, Shengyong; Luo, Yunping; Xiang, Rong; Tan, Xiaoyue

    2014-11-01

    Although Oct4 is known as a critical transcription factor involved in maintaining "stemness", its role in tumor metastasis is still controversial. Herein, we overexpressed and silenced Oct4 expression in two breast cancer cell lines, MDA-MB-231 and 4T1, separately. Our data showed that ectopic overexpression of Oct4 suppressed cell migration and invasion in vitro and the formation of metastatic lung nodules in vivo. Conversely, Oct4 downregulation increased the metastatic potential of breast cancer cells both in vitro and in vivo. Furthermore, we identified Rnd1 as the downstream target of Oct4 by ribonucleic acid sequencing (RNA-seq) analysis, which was significantly downregulated upon Oct4 overexpression. Chromatin immunoprecipitation assays revealed the binding of Oct4 to the promoter region of Rnd1 by ectopic overexpression of Oct4. Dual luciferase assays indicated that Oct4 overexpression suppressed transcriptional activity of the Rnd1 promoter. Moreover, overexpression of Rnd1 partially rescued the inhibitory effects of Oct4 on the migration and invasion of breast cancer cells. Overexpression of Rnd1 counteracted the influence of Oct4 on the formation of cell adhesion and lamellipodia, which implied a potential underlying mechanism involving Rnd1. In addition, we also found that overexpression of Oct4 led to an elevation of E-cadherin expression, even in 4T1 cells that possess a relatively high basal level of E-cadherin. Rnd1 overexpression impaired the promoting effects of Oct4 on E-cadherin expression in MDA-MB-231 cells. These results suggest that Oct4 affects the metastatic potential of breast cancer cells through Rnd1-mediated effects that influence cell motility and E-cadherin expression. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Overexpression of Myo1e in mouse podocytes enhances cellular endocytosis, migration, and adhesion.

    Science.gov (United States)

    Jin, Xia; Wang, Wenjing; Mao, Jianhua; Shen, Huijun; Fu, Haidong; Wang, Xia; Gu, Weizhong; Liu, Aimin; Yu, Huimin; Shu, Qiang; Du, Lizhong

    2014-02-01

    Podocytes are a terminally differentiated and highly specialized cell type in the glomerulus that forms a crucial component of the glomerular filtration barrier. Recently, Myo1e was identified in the podocytes of glomeruli. Myo1e podocyte-specific knockout mice exhibit proteinuria, podocyte foot process effacement, glomerular basement membrane disorganization, signs of chronic renal injury, and kidney inflammation. After overexpression of Myo1e in a conditionally immortalized mouse podocyte cell line (MPC5), podocyte migration was evaluated via transwell assay, endocytosis was evaluated using FITC-transferrin, and adhesion was evaluated using a detachment assay after puromycin aminonucleoside treatment. Myo1e overexpression significantly increased the adherence of podocytes. ANOVA analysis indicated significant differences for cell adhesion between the overexpression and control groups (overexpression vs. control, t = 11.3199, P = 0.005; overexpression vs. negative control, t = 12.0570, P = 0.0006). Overexpression of Myo1e inhibited puromycin aminonucleoside-induced podocyte detachment, and the number of cells remaining on the bottom of the culture plate increased. Cell migration was enhanced in Myo1e-overexpressing podocytes in the transwell migration assay. Internalization of FITC-transferrin also increased in Myo1e-overexpressing podocytes relative to control cells. Overexpression of Myo1e can enhance podocyte migration ability, endocytosis, and attachment to the glomerular basement membrane. Restoration of Myo1e expression in podocytes may therefore strengthen their functional integrity against environmental and mechanical injury. © 2013 Wiley Periodicals, Inc.

  17. Representing delayed force feedback as a combination of current and delayed states.

    Science.gov (United States)

    Avraham, Guy; Mawase, Firas; Karniel, Amir; Shmuelof, Lior; Donchin, Opher; Mussa-Ivaldi, Ferdinando A; Nisky, Ilana

    2017-10-01

    To adapt to deterministic force perturbations that depend on the current state of the hand, internal representations are formed to capture the relationships between forces experienced and motion. However, information from multiple modalities travels at different rates, resulting in intermodal delays that require compensation for these internal representations to develop. To understand how these delays are represented by the brain, we presented participants with delayed velocity-dependent force fields, i.e., forces that depend on hand velocity either 70 or 100 ms beforehand. We probed the internal representation of these delayed forces by examining the forces the participants applied to cope with the perturbations. The findings showed that for both delayed forces, the best model of internal representation consisted of a delayed velocity and current position and velocity. We show that participants relied initially on the current state, but with adaptation, the contribution of the delayed representation to adaptation increased. After adaptation, when the participants were asked to make movements with a higher velocity for which they had not previously experienced with the delayed force field, they applied forces that were consistent with current position and velocity as well as delayed velocity representations. This suggests that the sensorimotor system represents delayed force feedback using current and delayed state information and that it uses this representation when generalizing to faster movements. NEW & NOTEWORTHY The brain compensates for forces in the body and the environment to control movements, but it is unclear how it does so given the inherent delays in information transmission and processing. We examined how participants cope with delayed forces that depend on their arm velocity 70 or 100 ms beforehand. After adaptation, participants applied opposing forces that revealed a partially correct representation of the perturbation using the current and the

  18. Bcl-2 overexpression: effects on transmembrane calcium movement

    International Nuclear Information System (INIS)

    Rangaswami, Arun A.; Premack, Brett; Walleczek, Jan; Killoran, Pamela; Gardner, Phyllis; Knox, Susan J.

    1996-01-01

    calcium influx rate was measured as above. Apoptosis was measured by morphological, DNA fragmentation, and FACS analyses. Levels of Bcl-2 expression in the various cell types were quantified by Western Blot Analysis. Results: In both cell lines, Bcl-2 overexpression had no effect on the resting cytosolic calcium concentration. However, there was a 1.7 to 1.8 fold increase in the cytosolic calcium concentration in the Bcl-2 transfected cells following exposure to 0.5 μM thapsigargin (p<0.001), which was not observed in similarly treated parental or neomycin control transfected cells. Furthermore, this difference was only observed in cells incubated in media containing 2 mM extracellular calcium and was abrogated by chelation of external calcium with EGTA. Quantification of calcium influx rates by the manganese quench technique demonstrated enhanced calcium influx rates in Bcl-2 transfected cell lines both at rest and in response to depletion of cellular calcium stores by thapsigargin. Furthermore, neither hyper polarization of the cells by Valinomycin nor depolarization by isotonic potassium chloride abrogated the relative enhancement of calcium entry in the Bcl-2 over expressing cell lines as compared with the parental or neomycin transfected controls. Conclusion: These preliminary results suggest that Bcl-2 overexpression may contribute to chemo and radioresistance of tumor cells by altering capacitive calcium entry. Although Bcl-2 overexpression does not alter the resting calcium concentration, it does significantly enhance the resting calcium influx rate, suggesting that the dynamic equilibrium of calcium movement across the plasma membrane is significantly altered in cells which over express the Bcl-2 onco-protein. This perturbation is independent of the effect of Bcl-2 on plasma membrane hyper polarization. Given the importance of calcium in signaling a variety of cellular processes including cell division and differentiation, these findings may help to explain the

  19. Transmission delays in hardware clock synchronization

    Science.gov (United States)

    Shin, Kang G.; Ramanathan, P.

    1988-01-01

    Various methods, both with software and hardware, have been proposed to synchronize a set of physical clocks in a system. Software methods are very flexible and economical but suffer an excessive time overhead, whereas hardware methods require no time overhead but are unable to handle transmission delays in clock signals. The effects of nonzero transmission delays in synchronization have been studied extensively in the communication area in the absence of malicious or Byzantine faults. The authors show that it is easy to incorporate the ideas from the communication area into the existing hardware clock synchronization algorithms to take into account the presence of both malicious faults and nonzero transmission delays.

  20. A continuous time Cournot duopoly with delays

    International Nuclear Information System (INIS)

    Gori, Luca; Guerrini, Luca; Sodini, Mauro

    2015-01-01

    This paper extends the classical repeated duopoly model with quantity-setting firms of Bischi et al. (1998) by assuming that production of goods is subject to some gestation lags but exchanges take place continuously in the market. The model is expressed in the form of differential equations with discrete delays. By using some recent mathematical techniques and numerical experiments, results show some dynamic phenomena that cannot be observed when delays are absent. In addition, depending on the extent of time delays and inertia, synchronisation failure can arise even in the event of homogeneous firms.

  1. Delayed encephalopathy after acute carbon monoxide poisoning

    Directory of Open Access Journals (Sweden)

    Mehmet İbrahim Turan

    2014-03-01

    Full Text Available Carbon monoxide poisoning is a major cause of death following attempted suicide and accidental exposures. Although clinical presentation depends on the duration and the intensity of exposure, the assessment of the severity of intoxication is difficult. A small percentage of patients who show complete initial recovery may develop delayed neurological deficits. Delayed encephalopathy after acute carbon monoxide poisoning is a rare and poor prognosis neurologic disorders and there is no specific treatment. We present a case with early onset of delayed encephalopathy after acute carbon monoxide poisoning with typical cranial imaging findings in a child with atypical history and clinical presentation.

  2. Bubbling in delay-coupled lasers.

    Science.gov (United States)

    Flunkert, V; D'Huys, O; Danckaert, J; Fischer, I; Schöll, E

    2009-06-01

    We theoretically study chaos synchronization of two lasers which are delay coupled via an active or a passive relay. While the lasers are synchronized, their dynamics is identical to a single laser with delayed feedback for a passive relay and identical to two delay-coupled lasers for an active relay. Depending on the coupling parameters the system exhibits bubbling, i.e., noise-induced desynchronization, or on-off intermittency. We associate the desynchronization dynamics in the coherence collapse and low-frequency fluctuation regimes with the transverse instability of some of the compound cavity's antimodes. Finally, we demonstrate how, by using an active relay, bubbling can be suppressed.

  3. Travelling wave solutions in delayed cooperative systems

    International Nuclear Information System (INIS)

    Li, Bingtuan; Zhang, Liang

    2011-01-01

    We establish the existence of travelling wave solutions for delayed cooperative recursions that are allowed to have more than two equilibria. We define an important extended real number that is used to determine the speeds of travelling wave solutions. The results can be applied to a large class of delayed cooperative reaction–diffusion models. We show that for a delayed Lotka–Volterra reaction–diffusion competition model, there exists a finite positive number c * + that can be characterized as the slowest speed of travelling wave solutions connecting two mono-culture equilibria or connecting a mono-culture with the coexistence equilibrium

  4. Transcriptional delay stabilizes bistable gene networks.

    Science.gov (United States)

    Gupta, Chinmaya; López, José Manuel; Ott, William; Josić, Krešimir; Bennett, Matthew R

    2013-08-02

    Transcriptional delay can significantly impact the dynamics of gene networks. Here we examine how such delay affects bistable systems. We investigate several stochastic models of bistable gene networks and find that increasing delay dramatically increases the mean residence times near stable states. To explain this, we introduce a non-Markovian, analytically tractable reduced model. The model shows that stabilization is the consequence of an increased number of failed transitions between stable states. Each of the bistable systems that we simulate behaves in this manner.

  5. Increased isobutanol production in Saccharomyces cerevisiae by overexpression of genes in valine metabolism

    Directory of Open Access Journals (Sweden)

    Karhumaa Kaisa

    2011-07-01

    Full Text Available Abstract Background Isobutanol can be a better biofuel than ethanol due to its higher energy density and lower hygroscopicity. Furthermore, the branched-chain structure of isobutanol gives a higher octane number than the isomeric n-butanol. Saccharomyces cerevisiae was chosen as the production host because of its relative tolerance to alcohols, robustness in industrial fermentations, and the possibility for future combination of isobutanol production with fermentation of lignocellulosic materials. Results The yield of isobutanol was improved from 0.16 to 0.97 mg per g glucose by simultaneous overexpression of biosynthetic genes ILV2, ILV3, and ILV5 in valine metabolism in anaerobic fermentation of glucose in mineral medium in S. cerevisiae. Isobutanol yield was further improved by twofold by the additional overexpression of BAT2, encoding the cytoplasmic branched-chain amino-acid aminotransferase. Overexpression of ILV6, encoding the regulatory subunit of Ilv2, in the ILV2 ILV3 ILV5 overexpression strain decreased isobutanol production yield by threefold. In aerobic cultivations in shake flasks in mineral medium, the isobutanol yield of the ILV2 ILV3 ILV5 overexpression strain and the reference strain were 3.86 and 0.28 mg per g glucose, respectively. They increased to 4.12 and 2.4 mg per g glucose in yeast extract/peptone/dextrose (YPD complex medium under aerobic conditions, respectively. Conclusions Overexpression of genes ILV2, ILV3, ILV5, and BAT2 in valine metabolism led to an increase in isobutanol production in S. cerevisiae. Additional overexpression of ILV6 in the ILV2 ILV3 ILV5 overexpression strain had a negative effect, presumably by increasing the sensitivity of Ilv2 to valine inhibition, thus weakening the positive impact of overexpression of ILV2, ILV3, and ILV5 on isobutanol production. Aerobic cultivations of the ILV2 ILV3 ILV5 overexpression strain and the reference strain showed that supplying amino acids in cultivation media

  6. Mechanisms of MRP over-expression in four human lung-cancer cell lines and analysis of the MRP amplicon

    NARCIS (Netherlands)

    Eijdems, E. W.; de Haas, M.; Coco-Martin, J. M.; Ottenheim, C. P.; Zaman, G. J.; Dauwerse, H. G.; Breuning, M. H.; Twentyman, P. R.; Borst, P.; Baas, F.

    1995-01-01

    Some multidrug resistant cell lines over-express the gene encoding the multidrug-resistance-associated protein (MRP). In all cell lines reported thus far, over-expression is associated with gene amplification. We have studied the predominant mechanisms of MRP over-expression in 4 human lung-cancer

  7. OSCILLATION OF NONLINEAR DELAY DIFFERENCE EQUATIONS

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    This paper deals with the oscillatory properties of a class of nonlinear difference equations with several delays. Sufficient criteria in the form of infinite sum for the equations to be oscillatory are obtained.

  8. Compensating for telecommunication delays during robotic telerehabilitation.

    Science.gov (United States)

    Consoni, Leonardo J; Siqueira, Adriano A G; Krebs, Hermano I

    2017-07-01

    Rehabilitation robotic systems may afford better care and telerehabilitation may extend the use and benefits of robotic therapy to the home. Data transmissions over distance are bound by intrinsic communication delays which can be significant enough to deem the activity unfeasible. Here we describe an approach that combines unilateral robotic telerehabilitation and serious games. This approach has a modular and distributed design that permits different types of robots to interact without substantial code changes. We demonstrate the approach through an online multiplayer game. Two users can remotely interact with each other with no force exchanges, while a smoothing and prediction algorithm compensates motions for the delay in the Internet connection. We demonstrate that this approach can successfully compensate for data transmission delays, even when testing between the United States and Brazil. This paper presents the initial experimental results, which highlight the performance degradation with increasing delays as well as improvements provided by the proposed algorithm, and discusses planned future developments.

  9. Isolation Effect in Immediate and Delayed Recall

    Science.gov (United States)

    Bellezza, Francis S.; Cheney, Terry L.

    1973-01-01

    If the hypothesis of selective rehearsal is used to account for the isolation effect, then the recall of isolated items will depend both on the serial position of the isolated item and on whether recall is immediate or delayed. (Author)

  10. A simple chaotic delay differential equation

    International Nuclear Information System (INIS)

    Sprott, J.C.

    2007-01-01

    The simplest chaotic delay differential equation with a sinusoidal nonlinearity is described, including the route to chaos, Lyapunov exponent spectrum, and chaotic diffusion. It is prototypical of many other high-dimensional chaotic systems

  11. Time delay of quantum scattering processes

    International Nuclear Information System (INIS)

    Martin, P.A.

    1981-01-01

    The author presents various aspects of the theory of the time delay of scattering processes. The author mainly studies non-relativistic two-body scattering processes, first summarizing briefly the theory of simple scattering systems. (Auth.)

  12. Does Bilingualism Delay the Development of Dementia?

    Directory of Open Access Journals (Sweden)

    Amy L Atkinson

    2016-08-01

    Full Text Available It has been suggested that bilingualism (where individuals speak two languages may delay the development of dementia. However, much of the research is inconclusive. Some researchers have reported that bilingualism delays the onset and diagnosis of dementia, whilst other studies have found weak or even detrimental effects. This paper reviews a series of nine empirical studies, published up until March 2016, which investigated whether bilingualism significantly delays the onset of dementia. The article also explores whether the inconsistent findings can be attributed to differences in study designs or the definitions of bilingualism used between studies. Based on current evidence, it appears that lifelong bilingualism, where individuals frequently use both languages, may be protective against dementia. However, becoming bilingual in adulthood or using the second language infrequently is unlikely to substantially delay onset of the disease.

  13. Rich dynamics of discrete delay ecological models

    International Nuclear Information System (INIS)

    Peng Mingshu

    2005-01-01

    We study multiple bifurcations and chaotic behavior of a discrete delay ecological model. New form of chaos for the 2-D map is observed: the combination of potential period doubling and reverse period-doubling leads to cascading bubbles

  14. Four-channel delay generator model 5740

    International Nuclear Information System (INIS)

    Baumatz, D.; Milner, M.

    1978-01-01

    The 4-channel delay generator model 5740 generates 4-pulse groups in independent channels. The device offers the possibility of controlling both the time intervals between the pulses of a group and the rate of generation of groups

  15. Lauch of CERN particle accelerator delayed

    CERN Multimedia

    2007-01-01

    "Scientists seeking to uncover the secrets of the universe will have to wait a little longer after the CERN laboratory inSwitzerland yesterday confirmed a delay in tests of its massive new particle accelerator." (1 page)

  16. Diagnosis delay in tuberculosis and its consequences

    International Nuclear Information System (INIS)

    Habibullah, S.; Sheikh, M.A.; Sadiq, A.; Anwar, T.

    2004-01-01

    Objective: To find out the average duration from onset of symptoms to the diagnosis and treatment of tuberculosis, reasons for diagnostic delay, its consequences, association of variables and formulation of recommendations. Results: In this study it was found that average time from onset of initial symptoms to diagnosis and treatment of tuberculosis was 120 days. In 64% of the patients medical practitioners were responsible for delaying the diagnosis of tuberculosis. Loss of weight in 40% and haemoptysis is 21% were the consequences of diagnostic delay of tuberculosis. Delay in the diagnosis of tuberculosis was statistically significant in those patients who consulted private practitioners, and consequences of tuberculosis were severe in those patients who consulted late. (author)

  17. Variable Delay in port-Hamiltonian Telemanipulation

    NARCIS (Netherlands)

    Secchi, C; Stramigioli, Stefano; Fantuzzi, C.

    2006-01-01

    In several applications involving bilateral telemanipulation, master and slave act at different power scales. In this paper a strategy for passively dealing with variable communication delay in scaled port-Hamiltonian based telemanipulation over packet switched networks is proposed.

  18. Nonlinear Cournot duopoly with implementation delays

    International Nuclear Information System (INIS)

    Matsumoto, Akio; Szidarovszky, Ferenc

    2015-01-01

    We study the effects of two delays on the local as well as on global stability of nonlinear Cournot duopoly dynamics. The two major findings are an analytical construction of the stability switching curve on which stability is lost and the numerical confirmation of the birth of aperiodic global dynamics when the stationary state is locally unstable. The delays matters and can generate various dynamics ranging from simple to complicated dynamics.

  19. Delay in polling systems in heavy traffic

    Science.gov (United States)

    van der Mei, Robert D.

    1998-10-01

    We study the delay in asymmetric cyclic polling systems with general mixtures of gated and exhaustive service, with generally distributed service times and switch-over times, in heavy traffic. We obtain closed-form expressions for all moments of the delay incurred at each of the queues. The expressions are strikingly simple and can even be expressed as finite products of known factors. The results provide new insights into the heavy-traffic behavior of polling systems.

  20. Acceptable Channel Switching Delays for Mobile TV

    DEFF Research Database (Denmark)

    Fleury, Alexandre; Pedersen, Jakob Schou; Larsen, Lars Bo

    2011-01-01

    as well as three potential effect factors: the transition type, the test environment and the audiovisual content. The results show that delays longer than 5.7 seconds annoyed test participants, and that the transition type had a significant impact on the rating of channel switching delays. However......, neither the test environment nor the audiovisual content influenced the ratings significantly. Finally, a discussion of these results and directions for future research are proposed....

  1. Inverse Problems for Nonlinear Delay Systems

    Science.gov (United States)

    2011-03-15

    population dynamics. We consider the delay between birth and adulthood for neonate pea aphids and present a mathematical model that treats this delay as...which there is currently no known cure. For HIV, the core of the virus is composed of single-stranded viral RNA and protein components. As depicted in...at a CD4 receptor site and the viral core is injected into the cell. Once inside, the protein components enable transcription and integration of the

  2. The Strategic Perils of Delayed Differentiation

    OpenAIRE

    Krishnan S. Anand; Karan Girotra

    2007-01-01

    The value of delayed differentiation (also known as postponement) for a monopolist has been extensively studied in the operations literature. We analyze the case of (imperfectly) competitive markets with demand uncertainty, wherein the choice of supply chain configuration (i.e., early or delayed differentiation) is endogenous to the competing firms. We characterize firms' choices in equilibrium and analyze the effects of these choices on quantities sold, profits, consumer surplus, and welfare...

  3. Diagnosis delay in Libyan female breast cancer

    Directory of Open Access Journals (Sweden)

    Ermiah Eramah

    2012-08-01

    Full Text Available Abstract Aims To study the diagnosis delay and its impact on stage of disease among women with breast cancer on Libya. Methods 200 women, aged 22 to 75 years with breast cancer diagnosed during 2008–2009 were interviewed about the period from the first symptoms to the final histological diagnosis of breast cancer. This period (diagnosis time was categorized into 3 periods: 6 months. If diagnosis time was longer than 3 months, the diagnosis was considered delayed (diagnosis delay. Consultation time was the time taken to visit the general practitioner after the first symptoms. Retrospective preclinical and clinical data were collected on a form (questionnaire during an interview with each patient and from medical records. Results The median of diagnosis time was 7.5 months. Only 30.0% of patients were diagnosed within 3 months after symptoms. 14% of patients were diagnosed within 3–6 months and 56% within a period longer than 6 months. A number of factors predicted diagnosis delay: Symptoms were not considered serious in 27% of patients. Alternative therapy (therapy not associated with cancer was applied in 13.0% of the patients. Fear and shame prevented the visit to the doctor in 10% and 4.5% of patients, respectively. Inappropriate reassurance that the lump was benign was an important reason for prolongation of the diagnosis time. Diagnosis delay was associated with initial breast symptom(s that did not include a lump (p  Diagnosis delay was associated with bigger tumour size (p Conclusions Diagnosis delay is very serious problem in Libya. Diagnosis delay was associated with complex interactions between several factors and with advanced stages. There is a need for improving breast cancer awareness and training of general practitioners to reduce breast cancer mortality by promoting early detection. The treatment guidelines should pay more attention to the early phases of breast cancer. Especially, guidelines for good practices in managing

  4. Time delay in a multichannel formalism

    International Nuclear Information System (INIS)

    Haberzettl, Helmut; Workman, Ron

    2007-01-01

    We reexamine the time-delay formalism of Wigner, Eisenbud, and Smith, which was developed to analyze both elastic and inelastic resonances. An error in the paper of Smith has propagated through the literature. We correct this error and show how the results of Eisenbud and Smith are related. We also comment on some recent time-delay studies, based on Smith's erroneous interpretation of the Eisenbud result

  5. The reasons for delay lumbar puncture

    Directory of Open Access Journals (Sweden)

    MH. Lotfi

    2017-04-01

    Full Text Available Early diagnosis of meningitis and encephalitis and prompt initiation of appropriate therapy is vital and any delay will lead to high mortality and serious and permanent morbidity. The main purpose of this study was to evaluate the management of 220 patients with suspected central nervous system (CNS infections (meningitis and encephalitis to determine the percentage of patients’ suspected CNS infection undergo lumbar puncture in acceptable time (in accordance with conventional algorithms. In this descriptive study, patients with suspected CNS infections admitted to Bu-Ali and Qods hospitals, in the period July 2013 to December 2015 were studied. Information of 220 patients was collected. Continuous variables were summarized as means ± standard deviation and categorical variables as frequencies and percentages. Lumbar puncture (LP in patients was delayed in 200 cases (91%. Most common causes of delay in performing LP were prolongation of the process of determining patient needs to puncture, satisfying patients, CT scan delay and the delay in allowing LP by neurologist. In this study, delaying LP rate was higher than other studies. It seems certain pattern in assistants’ visits for counseling. CT requests and neurologic consultation before LP performed for all adult patients.

  6. Nuclear size and cell division delay

    International Nuclear Information System (INIS)

    Bird, R.P.

    1986-01-01

    Radiation-induced division delay has been linked to damage at the nuclear envelope. Further, cells in G 2 phase are drastically arrested by high LET radiation such that single particles traversing cell nuclei may produce measurable division delay. A modest effort was initiated using two related cell lines of different size, near-diploid cells and near-tetraploid cells of Chinese hamster origin, to compare their sensitivity for radiation-induced division delay. If the nuclear surface is the critical target, then a larger nuclear cross-section presented to an alpha-particle beam should exhibit delay induced by a lesser particle fluence. Preliminary estimates of the extent of delay in asynchronous cultures following low doses of gamma-irradiation or of alpha-irradiation were made by in-situ observation of the time of onset of mitosis and by fixation and staining of cultures to determine the mitotic index as a function of time after irradiation. The basic approach to evaluating division delay will be to use Colecemid to accumulate mitotic cells over a period of time

  7. Overexpression of the CC-type glutaredoxin, OsGRX6 affects hormone and nitrogen status in rice plants

    Directory of Open Access Journals (Sweden)

    Ashraf eEl-Kereamy

    2015-11-01

    Full Text Available Glutaredoxins (GRXs are small glutathione dependent oxidoreductases that belong to the Thioredoxin (TRX superfamily and catalyze the reduction of disulfide bonds of their substrate proteins. Plant GRXs include three different groups based on the motif sequence, namely CPYC, CGFS and CC-type proteins. The rice CC-type proteins, OsGRX6 was identified during the screening for genes whose expression changes depending on the level of available nitrate. Overexpression of OsGRX6 in rice displayed a semi-dwarf phenotype. The OsGRX6 overexpressors contain a higher nitrogen content than the wild type, indicating that OsGRX6 plays a role in homeostatic regulation of nitrogen use. Consistent with this, OsGRX6 overexpressors displayed delayed chlorophyll degradation and senescence compared to the wild type plants. To examine if the growth defect of these transgenic lines attribute to disturbed plant hormone actions, plant hormone levels were measured. The levels of two cytokinins (CKs, 2-isopentenyladenine and trans-zeatin, and gibberellin A1 (GA1 were increased in these lines. We also found that these transgenic lines were less sensitive to exogenously applied GA, suggesting that the increase in GA1 is a result of the feedback regulation. These data suggest that OsGRX6 affects hormone signaling and nitrogen status in rice plants.

  8. Overexpression of CYB5R3 and NQO1, two NAD+ -producing enzymes, mimics aspects of caloric restriction.

    Science.gov (United States)

    Diaz-Ruiz, Alberto; Lanasa, Michael; Garcia, Joseph; Mora, Hector; Fan, Frances; Martin-Montalvo, Alejandro; Di Francesco, Andrea; Calvo-Rubio, Miguel; Salvador-Pascual, Andrea; Aon, Miguel A; Fishbein, Kenneth W; Pearson, Kevin J; Villalba, Jose Manuel; Navas, Placido; Bernier, Michel; de Cabo, Rafael

    2018-04-28

    Calorie restriction (CR) is one of the most robust means to improve health and survival in model organisms. CR imposes a metabolic program that leads to increased stress resistance and delayed onset of chronic diseases, including cancer. In rodents, CR induces the upregulation of two NADH-dehydrogenases, namely NAD(P)H:quinone oxidoreductase 1 (Nqo1) and cytochrome b 5 reductase 3 (Cyb5r3), which provide electrons for energy metabolism. It has been proposed that this upregulation may be responsible for some of the beneficial effects of CR, and defects in their activity are linked to aging and several age-associated diseases. However, it is unclear whether changes in metabolic homeostasis solely through upregulation of these NADH-dehydrogenases have a positive impact on health and survival. We generated a mouse that overexpresses both metabolic enzymes leading to phenotypes that resemble aspects of CR including a modest increase in lifespan, greater physical performance, a decrease in chronic inflammation, and, importantly, protection against carcinogenesis, one of the main hallmarks of CR. Furthermore, these animals showed an enhancement of metabolic flexibility and a significant upregulation of the NAD + /sirtuin pathway. The results highlight the importance of these NAD + producers for the promotion of health and extended lifespan. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  9. Effect of secretory pathway gene overexpression on secretion of a fluorescent reporter protein in Aspergillus nidulans

    DEFF Research Database (Denmark)

    Schalén, Martin; Anyaogu, Diana Chinyere; Hoof, Jakob Blæsbjerg

    2016-01-01

    roles in the process have been identified through transcriptomics. The assignment of function to these genes has been enabled in combination with gene deletion studies. In this work, 14 genes known to play a role in protein secretion in filamentous fungi were overexpressed in Aspergillus nidulans....... The background strain was a fluorescent reporter secreting mRFP. The overall effect of the overexpressions could thus be easily monitored through fluorescence measurements, while the effects on physiology were determined in batch cultivations and surface growth studies. Results: Fourteen protein secretion...... pathway related genes were overexpressed with a tet-ON promoter in the RFP-secreting reporter strain and macromorphology, physiology and protein secretion were monitored when the secretory genes were induced. Overexpression of several of the chosen genes was shown to cause anomalies on growth, micro...

  10. The effect of aquaporin 5 overexpression on the Ras signaling pathway

    International Nuclear Information System (INIS)

    Woo, Janghee; Lee, Juna; Kim, Myoung Sook; Jang, Se Jin; Sidransky, David; Moon, Chulso

    2008-01-01

    Human aquaporin 5 (AQP5) has been shown to be overexpressed in multiple cancers, such as pancreatic cancer and colon cancer. Furthermore, it has been reported that ectopic expression of AQP5 leads to many phenotypic changes characteristic of transformation. However, the biochemical mechanism leading to transformation in AQP5-overexpressing cells has not been clearly elucidated. In this report, the overexpression of AQP5 in NIH3T3 cells demonstrated a significant effect on Ras activity and, thus, cell proliferation. Furthermore, this influence was shown to be mediated by phosphorylation of the PKA consensus site of AQP5. This is the first evidence demonstrating an association between AQP5 and a signaling pathway, namely the Ras signal transduction pathway, which may be the basis of the oncogenic properties seen in AQP-overexpressing cells

  11. Metabolic engineering of apple by overexpression of the MdMyb10 gene

    Directory of Open Access Journals (Sweden)

    Khaled A.L. Rihani

    2017-06-01

    In the present study, the flavonoid pathway was successfully modified in apple by overexpressing the MdMyb10 transcription factor to validate the hypothesis of increased effect on plant disease resistance.

  12. RESEARCH ARTICLE Co-overexpression of EpCAM and c-myc ...

    Indian Academy of Sciences (India)

    Purpose:The overexpression of epithelial cell adhesion molecule (EpCAM) ... Half LIM domain protein2), and the transcription factor Lef1 that is cleaved by presenilin-2 ..... and self-renewal capability, producing a rapidly dividing tumor mass.

  13. The Limitations to Delay-Insensitivity in Asynchronous Circuits

    National Research Council Canada - National Science Library

    Martin, Alain J

    1990-01-01

    ... produced are delay-insensitive (DI). A digital circuit is DI when its correct operation is independent of the delays in operators and in the wires connecting the operators, except that the delays are finite and positive...

  14. Lag synchronization of chaotic systems with time-delayed linear ...

    Indian Academy of Sciences (India)

    delayed linear terms via impulsive control is investigated. Based on the stability theory of impulsive delayed differen- tial equations, some sufficient conditions are obtained guaranteeing the synchronized behaviours between two delayed chaotic ...

  15. Apolipoprotein CIII overexpression exacerbates diet-induced obesity due to adipose tissue higher exogenous lipid uptake and retention and lower lipolysis rates.

    Science.gov (United States)

    Raposo, Helena F; Paiva, Adriene A; Kato, Larissa S; de Oliveira, Helena C F

    2015-01-01

    Hypertriglyceridemia is a common type of dyslipidemia found in obesity. However, it is not established whether primary hyperlipidemia can predispose to obesity. Evidences have suggested that proteins primarily related to plasma lipoprotein transport, such as apolipoprotein (apo) CIII and E, may significantly affect the process of body fat accumulation. We have previously observed an increased adiposity in response to a high fat diet (HFD) in mice overexpressing apoCIII. Here, we examined the potential mechanisms involved in this exacerbated response of apoCIII mice to the HFD. We measured body energy balance, tissue capacity to store exogenous lipids, lipogenesis and lipolysis rates in non-transgenic and apoCIII overexpressing mice fed a HFD during two months. Food intake, fat excretion and whole body CO2 production were similar in both groups. However, the adipose tissue mass (45 %) and leptin plasma levels (2-fold) were significantly greater in apoCIII mice. Lipogenesis rates were similar, while exogenous lipid retention was increased in perigonadal (2-fold) and brown adipose tissues (40 %) of apoCIII mice. In addition, adipocyte basal lipolysis (55 %) and in vivo lipolysis index (30 %) were significantly decreased in apoCIII mice. A fat tolerance test evidenced delayed plasma triglyceride clearance and greater transient availability of non-esterified fatty acids (NEFA) during the post-prandial state in the apoCIII mice plasma. Thus, apoCIII overexpression resulted in increased NEFA availability to adipose uptake and decreased adipocyte lipolysis, favoring lipid enlargement of adipose depots. We propose that plasma apoCIII levels represent a new risk factor for diet-induced obesity.

  16. Virtual unit delay for digital frequency adaptive T/4 delay phase-locked loop system

    DEFF Research Database (Denmark)

    Yang, Yongheng; Zhou, Keliang; Blaabjerg, Frede

    2016-01-01

    /processor with a fixed sampling rate considering the cost and complexity, where the number of unit delays that have been adopted should be an integer. For instance, in conventional digital control systems, a single-phase T/4 Delay Phase-Locked Loop (PLL) system takes 50 unit delays (i.e., in a 50-Hz system...... Delay PLL system should be done in its implementation. This process will result in performance degradation in the digital control system, as the exactly required number of delays is not realized. Hence, in this paper, a Virtual Unit Delay (VUD) has been proposed to address such challenges to the digital......Digital micro-controllers/processors enable the cost-effective control of grid-connected power converter systems in terms of system monitoring, signal processing (e.g., grid synchronization), control (e.g., grid current and voltage control), etc. Normally, the control is implemented in a micro-controller...

  17. The role for decorin in delayed-type hypersensitivity

    Science.gov (United States)

    Seidler, Daniela G.; Mohamed, Negia A.; Bocian, Carla; Stadtmann, Anika; Hermann, Sven; Schäfers, Klaus; Schäfers, Michael; Iozzo, Renato V.; Zarbock, Alexander; Götte, Martin

    2016-01-01

    Decorin, a small leucine-rich proteoglycan, regulates extracellular matrix organization, growth factor-mediated signaling and cell growth. As decorin may directly modulate immune responses, we investigated its role in a mouse model of contact allergy (oxazolone-mediated delayed-type hypersensitivity, DTH) in decorin-deficient (Dcn−/−) and wild-type mice. Dcn−/− mice showed a reduced ear swelling 24 hours after oxazolone treatment with a concurrent attenuation of leukocyte infiltration. These findings were corroborated by reduced glucose metabolism as determined by 18FDG uptake in positron emission tomography scans. Unexpectedly, polymorphonuclear leukocyte numbers in Dcn−/− blood vessels were significantly increased, accompanied by large numbers of flattened leukocytes adherent to the endothelium. Intravital microscopy, flow chamber and static adhesion assays confirmed increased adhesion and reduced transmigration of Dcn−/− leukocytes. Circulating blood neutrophil numbers were significantly increased in Dcn−/− mice 24 hours after DTH elicitation, but only moderately increased in wild-type mice. Expression of the pro-inflammatory cytokine TNF-α was reduced, while syndecan-1 and ICAM-1 were overexpressed in inflamed ears of Dcn−/− mice, indicating that these adhesion molecules could be responsible for increased leukocyte adhesion. Decorin treatment of endothelial cells increased tyrosine phosphorylation and reduced syndecan-1 expression. Notably, absence of syndecan-1 in a genetic background lacking decorin rescued the attenuated DTH phenotype of Dcn−/− mice. Collectively, these results implicate a role for decorin in mediating DTH responses by influencing polymorphonuclear leukocyte attachment to the endothelium. This occurs via two non-mutually exclusive mechanisms that involve a direct anti-adhesive effect on polymorphonuclear leukocytes and a negative regulation of ICAM-1 and syndecan-1 expression. PMID:22043007

  18. Effect of SOCS1 overexpression on RPE cell activation by proinflammatory cytokines.

    Science.gov (United States)

    Bazewicz, Magdalena; Draganova, Dafina; Makhoul, Maya; Chtarto, Abdel; Elmaleh, Valerie; Tenenbaum, Liliane; Caspers, Laure; Bruyns, Catherine; Willermain, François

    2016-09-06

    The purpose of this study was to investigate the in vitro effect of Suppressor Of Cytokine Signaling 1 (SOCS1) overexpression in retinal pigment epithelium (RPE) cells on their activation by pro-inflammatory cytokines IFNγ, TNFα and IL-17. Retinal pigment epithelium cells (ARPE-19) were stably transfected with the control plasmid pIRES2-AcGFP1 or the plasmid pSOCS1-IRES2-AcGFP1. They were stimulated by IFNγ (150ng/ml), TNFα (30ng/ml) or IL-17 (100ng/ml). The levels of SOCS1 mRNA were measured by real-time PCR. Signal Transducer and Activator of Transcription 1 (STAT1) phosphorylation and IκBα expression were analysed by western Blot (WB). IL-8 secretion was analysed by ELISA and expression of MHCII molecules and ICAM-1/CD54 by flow cytometry. Our data show that SOCS1 mRNA overexpression in RPE cells prevents IFNγ-induced SOCS1 mRNA increase and IFNγ-mediated STAT1 phosphorylation. Moreover, SOCS1 overexpression in RPE cells inhibits IFNγ-induced decrease of IL-8 secretion and prevents IFNγ-induced MHC II and ICAM1/CD54 upregulation. However, SOCS1 overexpression does not affect TNFα-induced IκBα degradation nor block TNFα-induced or IL-17-induced IL-8 secretion. On the contrary, IL-17-induced secretion is increased by SOCS1 overexpression. In conclusion, SOCS1 overexpression in RPE cells inhibits some IFNγ-mediated responses that lead to uveitis development. This notion raises the possibility that SOCS1 overexpression could be a novel target for treating non-infectious uveitis. However, some proinflammatory effects of TNFα and IL-17 stimulation on RPE are not blocked by SOCS1 overexpression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Enhanced Arabidopsis pattern-triggered immunity by overexpression of cysteine-rich receptor-like kinases.

    Science.gov (United States)

    Yeh, Yu-Hung; Chang, Yu-Hsien; Huang, Pin-Yao; Huang, Jing-Bo; Zimmerli, Laurent

    2015-01-01

    Upon recognition of microbe-associated molecular patterns (MAMPs) such as the bacterial flagellin (or the derived peptide flg22) by pattern-recognition receptors (PRRs) such as the FLAGELLIN SENSING2 (FLS2), plants activate the pattern-triggered immunity (PTI) response. The L-type lectin receptor kinase-VI.2 (LecRK-VI.2) is a positive regulator of Arabidopsis thaliana PTI. Cysteine-rich receptor-like kinases (CRKs) possess two copies of the C-X8-C-X2-C (DUF26) motif in their extracellular domains and are thought to be involved in plant stress resistance, but data about CRK functions are scarce. Here, we show that Arabidopsis overexpressing the LecRK-VI.2-responsive CRK4, CRK6, and CRK36 demonstrated an enhanced PTI response and were resistant to virulent bacteria Pseudomonas syringae pv. tomato DC3000. Notably, the flg22-triggered oxidative burst was primed in CRK4, CRK6, and CRK36 transgenics and up-regulation of the PTI-responsive gene FLG22-INDUCED RECEPTOR-LIKE 1 (FRK1) was potentiated upon flg22 treatment in CRK4 and CRK6 overexpression lines or constitutively increased by CRK36 overexpression. PTI-mediated callose deposition was not affected by overexpression of CRK4 and CRK6, while CRK36 overexpression lines demonstrated constitutive accumulation of callose. In addition, Pst DC3000-mediated stomatal reopening was blocked in CRK4 and CRK36 overexpression lines, while overexpression of CRK6 induced constitutive stomatal closure suggesting a strengthening of stomatal immunity. Finally, bimolecular fluorescence complementation and co-immunoprecipitation analyses in Arabidopsis protoplasts suggested that the plasma membrane localized CRK4, CRK6, and CRK36 associate with the PRR FLS2. Association with FLS2 and the observation that overexpression of CRK4, CRK6, and CRK36 boosts specific PTI outputs and resistance to bacteria suggest a role for these CRKs in Arabidopsis innate immunity.

  20. P53 overexpression and outcome of radiation therapy in head and neck cancers

    International Nuclear Information System (INIS)

    Kim, In Ah; Choi, Ihl Bhong; Kang, Ki Mun; Jang, Ji Young; Kim, Kyung Mi; Park, Kyung Shin; Kim, Young Shin; Kang, Chang Suk; Cho, Seung Ho; Kim, Hyung Tae

    1999-01-01

    Experimental studies have implicated the wild type p53 in cellular response to radiation. Whether altered p53 function can lead to changes in clinical radiocurability remains an area of ongoing study. This study was performed to investigate whether any correlation between change of p53 and outcome of curative radiation therapy in patients with head and neck cancers. Immunohistochemical analysis with a mouse monoclonal antibody (D0-7) specific for human p53 was used to detect to overexpression of protein in formalin fixed, paraffin-embedded tumor sample from 55 head and neck cancer patients treated with curative radiation therapy (median dose of 7020 cGy) from February 1988 to March 1996 at St. Mary's Hospital. Overexpression of p53 was correlated with locoregional control and survival using Kaplan-Meier method. A Cox regression multivariate analysis was performed that included all clinical variables and status of p53 expression. Thirty-seven (67.2%) patients showed overexpression of p53 by immunohistochemical staining in their tumor. One hundred percent of oral cavity, 76% of laryngeal, 66.7% of oropharyngeal, 66.7% of hypopharyngeal cancer showed p53 overexpression (p=0.05). The status of p53 had significant relationship with stage of disease (p=0.03) and history of smoking (p=0.001). The overexpression of p53 was not predictive of response rate to radiation therapy. The locoregional control was not significantly affected by p53 status. Overexpression of p53 didn't have any prognostic implication for disease free survival and overall survival. Primary site and stage of disease were significant prognostic factors for survival. The p53 overexpression as detected by immunohistochemical staining had significant correlation with stage, primary site of disease and smoking habit of patients. The p53 overexpression didn't have any predictive value for outcome of curative radiation therapy in a group of head and neck cancers

  1. Transgenic overexpression of adenine nucleotide translocase 1 protects ischemic hearts against oxidative stress.

    Science.gov (United States)

    Klumpe, Inga; Savvatis, Konstantinos; Westermann, Dirk; Tschöpe, Carsten; Rauch, Ursula; Landmesser, Ulf; Schultheiss, Heinz-Peter; Dörner, Andrea

    2016-06-01

    Ischemia impairs the adenine nucleotide translocase (ANT), which transports ADP and ATP across the inner mitochondrial membrane. We investigated whether ANT1 overexpression has protective effects on ischemic hearts. Myocardial infarction was induced in wild-type (WT) and heart-specific ANT1-transgenic (ANT1-TG) rats, and hypoxia was set in isolated cardiomyocytes. ANT1 overexpression reduced the myocardial infarct area and increased the survival rate of infarcted rats. Reduced ANT1 expression and increased 4-hydroxynonenal modification of ANT paralleled to impaired ANT function in infarcted WT hearts. ANT1 overexpression improved ANT expression and function. This was accompanied by reduced mitochondrial cytochrome C release and caspase-3 activation. ANT1-TG hearts suffered less from oxidative stress, as shown by lower protein carbonylation and 4-hydroxynonenal modification of ANT. ANT1 overexpression also increased cell survival of hypoxic cardiomyocytes and attenuated reactive oxygen species (ROS) production. This was linked to higher stability of mitochondrial membrane potential and lower activity of ROS detoxifying catalase. ANT1-TG cardiomyocytes also showed higher resistance against H2O2 treatment, which was independent of catalase activity. In conclusion, ANT1 overexpression compensates impaired ANT activity under oxygen-restricted conditions. It reduces ROS production and oxidative stress, stabilizes mitochondrial integrity, and increases survival, making ANT1 a component in ROS management and heart protection during ischemia. ANT1 overexpression reduces infarct size and increases survival after infarction. ANT1 overexpression compensates restricted ANT expression and function in infarcted hearts. Increased ANT1 expression enhances mitochondrial integrity. ANT1-overexpressing hearts reduce oxidative stress by decreasing ROS generation. ANT1 is a component in ROS management and heart protection.

  2. Overexpression screens identify conserved dosage chromosome instability genes in yeast and human cancer

    Science.gov (United States)

    Duffy, Supipi; Fam, Hok Khim; Wang, Yi Kan; Styles, Erin B.; Kim, Jung-Hyun; Ang, J. Sidney; Singh, Tejomayee; Larionov, Vladimir; Shah, Sohrab P.; Andrews, Brenda; Boerkoel, Cornelius F.; Hieter, Philip

    2016-01-01

    Somatic copy number amplification and gene overexpression are common features of many cancers. To determine the role of gene overexpression on chromosome instability (CIN), we performed genome-wide screens in the budding yeast for yeast genes that cause CIN when overexpressed, a phenotype we refer to as dosage CIN (dCIN), and identified 245 dCIN genes. This catalog of genes reveals human orthologs known to be recurrently overexpressed and/or amplified in tumors. We show that two genes, TDP1, a tyrosyl-DNA-phosphdiesterase, and TAF12, an RNA polymerase II TATA-box binding factor, cause CIN when overexpressed in human cells. Rhabdomyosarcoma lines with elevated human Tdp1 levels also exhibit CIN that can be partially rescued by siRNA-mediated knockdown of TDP1. Overexpression of dCIN genes represents a genetic vulnerability that could be leveraged for selective killing of cancer cells through targeting of an unlinked synthetic dosage lethal (SDL) partner. Using SDL screens in yeast, we identified a set of genes that when deleted specifically kill cells with high levels of Tdp1. One gene was the histone deacetylase RPD3, for which there are known inhibitors. Both HT1080 cells overexpressing hTDP1 and rhabdomyosarcoma cells with elevated levels of hTdp1 were more sensitive to histone deacetylase inhibitors valproic acid (VPA) and trichostatin A (TSA), recapitulating the SDL interaction in human cells and suggesting VPA and TSA as potential therapeutic agents for tumors with elevated levels of hTdp1. The catalog of dCIN genes presented here provides a candidate list to identify genes that cause CIN when overexpressed in cancer, which can then be leveraged through SDL to selectively target tumors. PMID:27551064

  3. P53 overexpression and outcome of radiation therapy in head and neck cancers

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In Ah; Choi, Ihl Bhong; Kang, Ki Mun; Jang, Ji Young; Kim, Kyung Mi; Park, Kyung Shin; Kim, Young Shin; Kang, Chang Suk; Cho, Seung Ho; Kim, Hyung Tae [College of Medicine, The Catholic Univ., Seoul (Korea, Republic of)

    1999-03-01

    Experimental studies have implicated the wild type p53 in cellular response to radiation. Whether altered p53 function can lead to changes in clinical radiocurability remains an area of ongoing study. This study was performed to investigate whether any correlation between change of p53 and outcome of curative radiation therapy in patients with head and neck cancers. Immunohistochemical analysis with a mouse monoclonal antibody (D0-7) specific for human p53 was used to detect to overexpression of protein in formalin fixed, paraffin-embedded tumor sample from 55 head and neck cancer patients treated with curative radiation therapy (median dose of 7020 cGy) from February 1988 to March 1996 at St. Mary's Hospital. Overexpression of p53 was correlated with locoregional control and survival using Kaplan-Meier method. A Cox regression multivariate analysis was performed that included all clinical variables and status of p53 expression. Thirty-seven (67.2%) patients showed overexpression of p53 by immunohistochemical staining in their tumor. One hundred percent of oral cavity, 76% of laryngeal, 66.7% of oropharyngeal, 66.7% of hypopharyngeal cancer showed p53 overexpression (p=0.05). The status of p53 had significant relationship with stage of disease (p=0.03) and history of smoking (p=0.001). The overexpression of p53 was not predictive of response rate to radiation therapy. The locoregional control was not significantly affected by p53 status. Overexpression of p53 didn't have any prognostic implication for disease free survival and overall survival. Primary site and stage of disease were significant prognostic factors for survival. The p53 overexpression as detected by immunohistochemical staining had significant correlation with stage, primary site of disease and smoking habit of patients. The p53 overexpression didn't have any predictive value for outcome of curative radiation therapy in a group of head and neck cancers.

  4. Overexpression of K-p21Ras play a prominent role in lung cancer

    Science.gov (United States)

    Zhang, Peng-bo; Zhou, Xin-liang; Yang, Ju-lun

    2018-06-01

    The proto-oncogene ras product, p21Ras, has been found overexpression in many human tumors. However, the subtypes of overexpressed p21Ras still remain unclear. The purpose of this study was to investigate overexpressed isoforms of p21Ras and their roles in the progress of lung cancer. Method: The expression of total p21Ras in normal lung tissues and lung cancers was determined by immunohistochemically staining with monoclonal antibody (Mab) KGHR-1 which could recognize and broad spectrum reaction with the (K/H/N) ras protein. Then, the isoforms of p21Ras was examined by specific Mab for each p21Ras subtypes. Results: Low expression of total p21Ras was found in 26.67% (8/30) of normal lung tissues, and 81.31% (87/107) of adenocarcinoma harbored overexpressed total p21Ras. Besides, 70.00% (35/50) of squamous cell carcinoma were detected overexpressed total p21Ras. In addition, 122 lung cancer tissues from overexpression of total p21Ras protein were selected to detect the expression of each subtype. And all the 122 lung cancer tissues were K-p21Ras overexpression. Moreover, there was a statistical significance difference between the expression level of total p21Ras and differentiation, and the same results were observed between the expression level of total p21Ras and lymph node metastasis (P0.05). Conclusions: Overexpression of K-p21Ras plays a prominent role in the progress of lung cancer and it is suggested that the p21Ras could serve as a promising treatment target in lung cancer.

  5. The production of nitric oxide in EL4 lymphoma cells overexpressing growth hormone.

    Science.gov (United States)

    Arnold, Robyn E; Weigent, Douglas A

    2003-01-01

    Growth hormone (GH) is produced by immunocompetent cells and has been implicated in the regulation of a multiplicity of functions in the immune system involved in growth and activation. However, the actions of endogenous or lymphocyte GH and its contribution to immune reactivity when compared with those of serum or exogenous GH are still unclear. In the present study, we overexpressed lymphocyte GH in EL4 lymphoma cells, which lack the GH receptor (GHR), to determine the role of endogenous GH in nitric oxide (NO) production and response to genotoxic stress. Western blot analysis demonstrated that the levels of GH increased approximately 40% in cells overexpressing GH (GHo) when compared with cells with vector alone. The results also show a substantial increase in NO production in cells overexpressing GH that could be blocked by N(G)-monomethyl-L-arginine (L-NMMA), an L-arginine analogue that competitively inhibits all three isoforms of nitric oxide synthase (NOS). No evidence was obtained to support an increase in peroxynitrite in cells overexpressing GH. Overexpression of GH increased NOS activity, inducible nitric oxide synthase (iNOS) promoter activity, and iNOS protein expression, whereas endothelial nitric oxide synthase and neuronal nitric oxide synthase protein levels were essentially unchanged. In addition, cells overexpressing GH showed increased arginine transport ability and intracellular arginase activity when compared with control cells. GH overexpression appeared to protect cells from the toxic effects of the DNA alkylating agent methyl methanesulfonate. This possibility was suggested by maintenance of the mitochondrial transmembrane potential in cells overexpressing GH when compared with control cells that could be blocked by L-NMMA. Taken together, the data support the notion that lymphocyte GH, independently of the GH receptor, may play a key role in the survival of lymphocytes exposed to stressful stimuli via the production of NO.

  6. Bcl-2 and Bcl-xL overexpression inhibits cytochrome c release, activation of multiple caspases, and virus release following coxsackievirus B3 infection

    International Nuclear Information System (INIS)

    Carthy, Christopher M.; Yanagawa, Bobby; Luo Honglin; Granville, David J.; Yang, Decheng; Cheung, Paul; Cheung, Caroline; Esfandiarei, Mitra; Rudin, Charles M.; Thompson, Craig B.; Hunt, David W.C.; McManus, Bruce M.

    2003-01-01

    Coxsackievirus B3, a cytopathic virus in the family Picornaviridae, induces degenerative changes in host cell morphology. Here we demonstrate cytochrome c release and caspases-2, -3, -6, -7, -8, and -9 processing. Enforced Bcl-2 and Bcl-xL expression markedly reduced release of cytochrome c, presentation of the mitochondrial epitope 7A6, and depressed caspase activation following infection. In comparison, cell death using TRAIL ligand caused caspase-8 processing prior to cytochrome c release and executioner caspases and cell death was only partially rescued by Bcl-2 and Bcl-xL overexpression. Disruption of the mitochondrial inner membrane potential following CVB3 infection was not inhibited by zVAD.fmk treatment. Bcl-2 or Bcl-xL overexpression or zVAD.fmk treatment delayed the loss of host cell viability and decreased progeny virus release following infection. Our data suggest that mitochondrial release of cytochrome c may be an important early event in caspase activation in CVB3 infection, and, as such, may contribute to the loss of host-cell viability and progeny virus release

  7. No dramatic age-related loss of hair cells and spiral ganglion neurons in Bcl-2 over-expression mice or Bax null mice

    Directory of Open Access Journals (Sweden)

    Ohlemiller Kevin K

    2010-07-01

    Full Text Available Abstract Age-related decline of neuronal function is associated with age-related structural changes. In the central nervous system, age-related decline of cognitive performance is thought to be caused by synaptic loss instead of neuronal loss. However, in the cochlea, age-related loss of hair cells and spiral ganglion neurons (SGNs is consistently observed in a variety of species, including humans. Since age-related loss of these cells is a major contributing factor to presbycusis, it is important to study possible molecular mechanisms underlying this age-related cell death. Previous studies suggested that apoptotic pathways were involved in age-related loss of hair cells and SGNs. In the present study, we examined the role of Bcl-2 gene in age-related hearing loss. In one transgenic mouse line over-expressing human Bcl-2, there were no significant differences between transgenic mice and wild type littermate controls in their hearing thresholds during aging. Histological analysis of the hair cells and SGNs showed no significant conservation of these cells in transgenic animals compared to the wild type controls during aging. These data suggest that Bcl-2 overexpression has no significant effect on age-related loss of hair cells and SGNs. We also found no delay of age-related hearing loss in mice lacking Bax gene. These findings suggest that age-related hearing loss is not through an apoptotic pathway involving key members of Bcl-2 family.

  8. Overexpression of HARDY, an AP2/ERF gene from Arabidopsis, improves drought and salt tolerance by reducing transpiration and sodium uptake in transgenic Trifolium alexandrinum L.

    Science.gov (United States)

    Abogadallah, Gaber M; Nada, Reham M; Malinowski, Robert; Quick, Paul

    2011-06-01

    Trifolium alexandrinum L. was transformed with the Arabidopsis HARDY gene that belongs to the stress-related AP2/ERF (APETALA2/ethylene responsive element binding factors) superfamily of transcription factors. The fresh weights of the transgenic lines L2 and L3 were improved by 42 and 55% under drought stress and by 38 and 95% under salt stress compared to the wild type, respectively. The dry weights were similarly improved. Overexpression of HARDY improved the instantaneous water use efficiency (WUE) under drought stress by reducing transpiration (E) and under salt stress by improving photosynthesis (A), through reducing Na+ accumulation in leaves, and reducing E. However, HARDY improved the growth of drought-stressed transgenic plants as compared to the wild type by delaying water depletion from soil and preventing rapid decline in A. L2 and L3 had thicker stems and in case of L3, more xylem rows per vascular bundle, which may have made L3 more resistant to lodging in the field. Field performance of L2 and L3 under combined drought and salt stress was significantly better than that of the wild type in terms of fresh and dry weights (40%, 46% and 31%, 40%, respectively). The results provide further evidence for the efficiency of overexpression of a single gene in improving tolerance to abiotic stress under field conditions.

  9. Improving Delay-Range-Dependent Stability Condition for Systems with Interval Time-Varying Delay

    Directory of Open Access Journals (Sweden)

    Wei Qian

    2013-01-01

    Full Text Available This paper discusses the delay-range-dependent stability for systems with interval time-varying delay. Through defining the new Lyapunov-Krasovskii functional and estimating the derivative of the LKF by introducing new vectors, using free matrices and reciprocally convex approach, the new delay-range-dependent stability conditions are obtained. Two well-known examples are given to illustrate the less conservatism of the proposed theoretical results.

  10. Leveraging delay discounting for health: Can time delays influence food choice?

    Science.gov (United States)

    Appelhans, Bradley M; French, Simone A; Olinger, Tamara; Bogucki, Michael; Janssen, Imke; Avery-Mamer, Elizabeth F; Powell, Lisa M

    2018-03-15

    Delay discounting, the tendency to choose smaller immediate rewards over larger delayed rewards, is theorized to promote consumption of immediately rewarding but unhealthy foods at the expense of long-term weight maintenance and nutritional health. An untested implication of delay discounting models of decision-making is that selectively delaying access to less healthy foods may promote selection of healthier (immediately available) alternatives, even if they may be less desirable. The current study tested this hypothesis by measuring healthy versus regular vending machine snack purchasing before and during the implementation of a 25-s time delay on the delivery of regular snacks. Purchasing was also examined under a $0.25 discount on healthy snacks, a $0.25 tax on regular snacks, and the combination of both pricing interventions with the 25-s time delay. Across 32,019 vending sales from three separate vending locations, the 25-s time delay increased healthy snack purchasing from 40.1% to 42.5%, which was comparable to the impact of a $0.25 discount (43.0%). Combining the delay and the discount had a roughly additive effect (46.0%). However, the strongest effects were seen under the $0.25 tax on regular snacks (53.7%) and the combination of the delay and the tax (50.2%). Intervention effects varied substantially between vending locations. Importantly, time delays did not harm overall vending sales or revenue, which is relevant to the real-world feasibility of this intervention. More investigation is needed to better understand how the impact of time delays on food choice varies across populations, evaluate the effects of time delays on beverage vending choices, and extend this approach to food choices in contexts other than vending machines. ClinicalTrials.gov, NCT02359916. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Prediction of recombinant protein overexpression in Escherichia coli using a machine learning based model (RPOLP).

    Science.gov (United States)

    Habibi, Narjeskhatoon; Norouzi, Alireza; Mohd Hashim, Siti Z; Shamsir, Mohd Shahir; Samian, Razip

    2015-11-01

    Recombinant protein overexpression, an important biotechnological process, is ruled by complex biological rules which are mostly unknown, is in need of an intelligent algorithm so as to avoid resource-intensive lab-based trial and error experiments in order to determine the expression level of the recombinant protein. The purpose of this study is to propose a predictive model to estimate the level of recombinant protein overexpression for the first time in the literature using a machine learning approach based on the sequence, expression vector, and expression host. The expression host was confined to Escherichia coli which is the most popular bacterial host to overexpress recombinant proteins. To provide a handle to the problem, the overexpression level was categorized as low, medium and high. A set of features which were likely to affect the overexpression level was generated based on the known facts (e.g. gene length) and knowledge gathered from related literature. Then, a representative sub-set of features generated in the previous objective was determined using feature selection techniques. Finally a predictive model was developed using random forest classifier which was able to adequately classify the multi-class imbalanced small dataset constructed. The result showed that the predictive model provided a promising accuracy of 80% on average, in estimating the overexpression level of a recombinant protein. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Overexpression of NIMA-related kinase 2 is associated with poor prognoses in malignant glioma.

    Science.gov (United States)

    Liu, Huajie; Liu, Bin; Hou, Xianzeng; Pang, Bo; Guo, Pengbo; Jiang, Wanli; Ding, Qian; Zhang, Rui; Xin, Tao; Guo, Hua; Xu, Shangchen; Pang, Qi

    2017-05-01

    Eleated expression of NIMA-related kinase 2 (NEK2) was frequently observed in a variety of malignant cancers, and it appears to be involved in the initiation, maintenance, progression, metastasis of cancer and is positively associated with poor prognosis. We sought to investigate NEK2 expression and its predictive roles in malignant gliomas, and study the correlation of NEK2 protein expression with proliferation, clinical parameters, overall survival and some other parameters. We investigate NEK2 protein expression in 99 samples of malignant gliomas, including 35 WHO grade II, 22 grade III, and 42 grade IV gliomas, by immunohistochemistry and western blot (n = 50). We then made correlative analysis of protein overexpression using the Kaplan-Meier method, Log rank test, and Cox proportional-hazards model analysis. NEK2 protein was overexpressed in malignant gliomas, but not in normal brain tissues. Overexpression of NEK2 correlated with malignancy, proliferation and adverse overall survival in gliomas. Moreover, chemotherapy, resection extent and WHO grade also correlate with overall survival in gliomas. However, within WHO grade II glioma subgroup, NEK2 overexpression showed no impact on overall survival. The present study firstly reveals that NEK2 protein is widely overexpressed in gliomas. NEK2 overexpression correlates significantly with malignancy (WHO grades), proliferation (Ki-67) and prognosis in malignant gliomas. NEK2 is a potential gene therapy target and prognostic indicator.

  13. Extending the Impact of RAC1b Overexpression to Follicular Thyroid Carcinomas

    Directory of Open Access Journals (Sweden)

    Márcia Faria

    2016-01-01

    Full Text Available RAC1b is a hyperactive variant of the small GTPase RAC1 known to be a relevant molecular player in different cancers. Previous studies from our group lead to the evidence that its overexpression in papillary thyroid carcinoma (PTC is associated with an unfavorable prognosis. In the present study, we intended to extend the analysis of RAC1b expression to thyroid follicular neoplasms and to seek for clinical correlations. RAC1b expression levels were determined by RT-qPCR in thyroid follicular tumor samples comprising 23 follicular thyroid carcinomas (FTCs and 33 follicular thyroid adenomas (FTAs. RAC1b was found to be overexpressed in 33% of carcinomas while no RAC1b overexpression was documented among follicular adenomas. Patients with a diagnosis of FTC were divided into two groups based on longitudinal evolution and final outcome. RAC1b overexpression was significantly associated with both the presence of distant metastases (P = 0.01 and poorer clinical outcome (P = 0.01 suggesting that, similarly to that previously found in PTCs, RAC1b overexpression in FTCs is also associated with worse outcomes. Furthermore, the absence of RAC1b overexpression in follicular adenomas hints its potential as a molecular marker likely to contribute, in conjunction with other putative markers, to the preoperative differential diagnosis of thyroid follicular lesions.

  14. Attenuation of teratoma formation by p27 overexpression in induced pluripotent stem cells.

    Science.gov (United States)

    Matsu-ura, Toru; Sasaki, Hiroshi; Okada, Motoi; Mikoshiba, Katsuhiko; Ashraf, Muhammad

    2016-02-15

    Pluripotent stem cells, such as embryonic stem cells or induced pluripotent stem cells, have a great potential for regenerative medicine. Induced pluripotent stem cells, in particular, are suitable for replacement of tissue by autologous transplantation. However, tumorigenicity is a major risk in clinical application of both embryonic stem cells and induced pluripotent stem cells. This study explores the possibility of manipulating the cell cycle for inhibition of tumorigenicity. We genetically modified mouse induced pluripotent stem cells (miPSCs) to overexpress p27 tumor suppressor and examined their proliferation rate, gene expression, cardiac differentiation, tumorigenicity, and therapeutic potential in a mouse model of coronary artery ligation. Overexpression of p27 inhibited cell division of miPSCs, and that inhibition was dependent on the expression level of p27. p27 overexpressing miPSCs had pluripotency characteristics but lost stemness earlier than normal miPSCs during embryoid body and teratoma formation. These cellular characteristics led to none or smaller teratoma when the cells were injected into nude mice. Transplantation of both miPSCs and p27 overexpressing miPSCs into the infarcted mouse heart reduced the infarction size and improved left ventricular function. The overexpression of p27 attenuated tumorigenicity by reducing proliferation and earlier loss of stemness of miPSCs. The overexpression of p27 did not affect pluripotency and differentiation characteristics of miPSC. Therefore, regulation of the proliferation rate of miPSCs offers great therapeutic potential for repair of the injured myocardium.

  15. Energetic heavy ions overcome tumor radioresistance caused by overexpression of Bcl-2

    International Nuclear Information System (INIS)

    Hamada, Nobuyuki; Hara, Takamitsu; Omura-Minamisawa, Motoko; Funayama, Tomoo; Sakashita, Tetsuya; Sora, Sakura; Yokota, Yuichiro; Nakano, Takashi

    2008-01-01

    Background and purpose: Overexpression of Bcl-2 is frequent in human cancers and has been associated with radioresistance. Here we investigated the potential impact of heavy ions on Bcl-2 overexpressing tumors. Materials and methods: Bcl-2 cells (Bcl-2 overexpressing HeLa cells) and Neo cells (neomycin resistant gene-expressing HeLa cells) exposed to γ-rays or heavy ions were assessed for the clonogenic survival, apoptosis and cell cycle distribution. Results: Whereas Bcl-2 cells were more resistant to γ-rays (0.2 keV/μm) and helium ions (16.2 keV/μm) than Neo cells, heavy ions (76.3-1610 keV/μm) yielded similar survival regardless of Bcl-2 overexpression. Carbon ions (108 keV/μm) decreased the difference in the apoptotic incidence between Bcl-2 and Neo cells, and prolonged G 2 /M arrest that occurred more extensively in Bcl-2 cells than in Neo cells. Conclusions: High-LET heavy ions overcome tumor radioresistance caused by Bcl-2 overexpression, which may be explained at least in part by the enhanced apoptotic response and prolonged G 2 /M arrest. Thus, heavy-ion therapy may be a promising modality for Bcl-2 overexpressing radioresistant tumors

  16. Overexpression of allene oxide cyclase improves the biosynthesis of artemisinin in Artemisia annua L.

    Directory of Open Access Journals (Sweden)

    Xu Lu

    Full Text Available Jasmonates (JAs are important signaling molecules in plants and play crucial roles in stress responses, secondary metabolites' regulation, plant growth and development. In this study, the promoter of AaAOC, which was the key gene of jasmonate biosynthetic pathway, had been cloned. GUS staining showed that AaAOC was expressed ubiquitiously in A. annua. AaAOC gene was overexpressed under control of 35S promoter. RT-Q-PCR showed that the expression levels of AaAOC were increased from 1.6- to 5.2-fold in AaAOC-overexpression transgenic A. annua. The results of GC-MS showed that the content of endogenous jasmonic acid (JA was 2- to 4.7-fold of the control level in AaAOC-overexpression plants. HPLC showed that the contents of artemisinin, dihydroartemisinic acid and artemisinic acid were increased significantly in AaAOC-overexpression plants. RT-Q-PCR showed that the expression levels of FPS (farnesyl diphosphate synthase, CYP71AV1 (cytochrome P450 dependent hydroxylase and DBR2 (double bond reductase 2 were increased significantly in AaAOC-overexpression plants. All data demonstrated that increased endogenous JA could significantly promote the biosynthesis of artemisinin in AaAOC-overexpression transgenic A. annua.

  17. Extending the Impact of RAC1b Overexpression to Follicular Thyroid Carcinomas

    Science.gov (United States)

    Faria, Márcia; Capinha, Liliana; Simões-Pereira, Joana; Bugalho, Maria João; Silva, Ana Luísa

    2016-01-01

    RAC1b is a hyperactive variant of the small GTPase RAC1 known to be a relevant molecular player in different cancers. Previous studies from our group lead to the evidence that its overexpression in papillary thyroid carcinoma (PTC) is associated with an unfavorable prognosis. In the present study, we intended to extend the analysis of RAC1b expression to thyroid follicular neoplasms and to seek for clinical correlations. RAC1b expression levels were determined by RT-qPCR in thyroid follicular tumor samples comprising 23 follicular thyroid carcinomas (FTCs) and 33 follicular thyroid adenomas (FTAs). RAC1b was found to be overexpressed in 33% of carcinomas while no RAC1b overexpression was documented among follicular adenomas. Patients with a diagnosis of FTC were divided into two groups based on longitudinal evolution and final outcome. RAC1b overexpression was significantly associated with both the presence of distant metastases (P = 0.01) and poorer clinical outcome (P = 0.01) suggesting that, similarly to that previously found in PTCs, RAC1b overexpression in FTCs is also associated with worse outcomes. Furthermore, the absence of RAC1b overexpression in follicular adenomas hints its potential as a molecular marker likely to contribute, in conjunction with other putative markers, to the preoperative differential diagnosis of thyroid follicular lesions. PMID:27127508

  18. Derivation and computation of discrete-delay and continuous-delay SDEs in mathematical biology.

    Science.gov (United States)

    Allen, Edward J

    2014-06-01

    Stochastic versions of several discrete-delay and continuous-delay differential equations, useful in mathematical biology, are derived from basic principles carefully taking into account the demographic, environmental, or physiological randomness in the dynamic processes. In particular, stochastic delay differential equation (SDDE) models are derived and studied for Nicholson's blowflies equation, Hutchinson's equation, an SIS epidemic model with delay, bacteria/phage dynamics, and glucose/insulin levels. Computational methods for approximating the SDDE models are described. Comparisons between computational solutions of the SDDEs and independently formulated Monte Carlo calculations support the accuracy of the derivations and of the computational methods.

  19. Global synchronization criteria with channel time-delay for chaotic time-delay system

    International Nuclear Information System (INIS)

    Sun Jitao

    2004-01-01

    Based on the Lyapunov stabilization theory, matrix measure, and linear matrix inequality (LMIs), this paper studies the chaos synchronization of time-delay system using the unidirectional linear error feedback coupling with time-delay. Some generic conditions of chaos synchronization with time-delay in the transmission channel is established. The chaotic Chua's circuit is used for illustration, where the coupling parameters are determined according to the criteria under which the global chaos synchronization of the time-delay coupled systems is achieved

  20. Prehospital delay in acute coronary syndrome--an analysis of the components of delay

    DEFF Research Database (Denmark)

    Ottesen, Michael Mundt; Dixen, Ulrik; Torp-Pedersen, Christian

    2004-01-01

    BACKGROUND: Prompt hospital admission is essential when treating acute coronary syndrome. Delay prior to admission is unnecessarily long. Therefore, a thorough scrutiny of the influence of characteristics, circumstantial and subjective variables on elements of prehospital delay among patients...... admitted with acute coronary syndrome is warranted. METHODS: A structured interview was conducted on 250 consecutive patients admitted alive with acute coronary syndrome. RESULTS: Median prehospital, decision, physician and transportation delays were 107, 74, 25 and 22 min, respectively. Women (n=77) had...... of acute coronary syndrome among women, and thereby contributes to unnecessary long delay to treatment. The patient's prior experience and interpretation has a significant influence on behaviour....

  1. Extension of mouse lifespan by overexpression of catalase.

    Science.gov (United States)

    Schriner, Samuel E; Linford, Nancy J

    2006-06-01

    The free radical theory of aging was originally proposed 50 years ago, and is arguably the most popular mechanism explaining the aging process. According to this theory, aging results from the progressive decline in organ function due to the damage generated by reactive oxygen species (ROS). These chemical species are a normal part of metabolism, and a group of enzymes exists to protect cells against their toxic effects. One of these species is hydrogen peroxide (H(2)O(2)), which can be degraded by catalase. To determine the role of hydrogen peroxide in aging and its importance in different subcellular compartments, transgenic mice were developed with increased catalase activities localized to the peroxisome (PCAT), nucleus (NCAT), or mitochondrion (MCAT). The largest effect on lifespan was found in MCAT animals, with a 20% increase in median lifespan and a 10% increase in the maximum lifespan. A more modest effect was seen in PCAT animals, and no significant change was found in NCAT animals. Upon further examination of the MCAT mice, it was found that H(2)O(2) production and H(2)O(2)-induced aconitase inactivation were attenuated, oxidative damage and the development of mitochondrial deletions were reduced, and cardiac pathology and cataract development were delayed. These results are consistent with a role of H(2)O(2) in the development of pathology and in the limitation of mouse lifespan. They also demonstrate the importance of mitochondria as a source, and possible target, of ROS.

  2. Impulsive control of time-delay systems using delayed impulse and its application to impulsive master-slave synchronization

    International Nuclear Information System (INIS)

    Sun Jitao; Han Qinglong; Jiang Xiefu

    2008-01-01

    This Letter is concerned with impulsive control of a class of nonlinear time-delay systems. Some uniform stability criteria for the closed-loop time-delay system under delayed impulsive control are derived by using piecewise Lyapunov functions. Then the criteria are applied to impulsive master-slave synchronization of some secure communication systems with transmission delays and sample delays under delayed impulsive control. Two numerical examples are given to illustrate the effectiveness of the derived results

  3. Putative sugarcane FT/TFL1 genes delay flowering time and alter reproductive architecture in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Carla P. Coelho

    2014-05-01

    Full Text Available Agriculturally important grasses such as rice, maize and sugarcane are evolutionarily distant from Arabidopsis, yet some components of the floral induction process are highly conserved. Flowering in sugarcane is an important factor that negatively affects cane yield and reduces sugar/ethanol production from this important perennial bioenergy crop. Comparative studies have facilitated the identification and characterization of putative orthologs of key flowering time genes in sugarcane, a complex polyploid plant whose genome has yet to be sequenced completely. Using this approach we identified phosphatidylethanolamine-binding protein (PEBP gene family members in sugarcane that are similar to the archetypical FT and TFL1 genes of Arabidopsis that play an essential role in controlling the transition from vegetative to reproductive growth. Expression analysis of ScTFL1, which falls into the TFL1-clade of floral repressors, showed transcripts in developing leaves surrounding the shoot apex but not at the apex itself. ScFT1 was detected in immature leaves and apical regions of vegetatively growing plants and, after the floral transition, expression also occurred in mature leaves. Ectopic over-expression of ScTFL1 in Arabidopsis caused delayed flowering in Arabidopsis, as might be expected for a gene related to TFL1. In addition, lines with the latest flowering phenotype exhibited aerial rosette formation. Unexpectedly, over-expression of ScFT1, which has greatest similarity to the florigen-encoding FT, also caused a delay in flowering. This preliminary analysis of divergent sugarcane FT and TFL1 gene family members from Saccharum spp. suggests that their expression patterns and roles in the floral transition has diverged from the predicted role of similar PEBP family members.

  4. Putative sugarcane FT/TFL1 genes delay flowering time and alter reproductive architecture in Arabidopsis.

    Science.gov (United States)

    Coelho, Carla P; Minow, Mark A A; Chalfun-Júnior, Antonio; Colasanti, Joseph

    2014-01-01

    Agriculturally important grasses such as rice, maize, and sugarcane are evolutionarily distant from Arabidopsis, yet some components of the floral induction process are highly conserved. Flowering in sugarcane is an important factor that negatively affects cane yield and reduces sugar/ethanol production from this important perennial bioenergy crop. Comparative studies have facilitated the identification and characterization of putative orthologs of key flowering time genes in sugarcane, a complex polyploid plant whose genome has yet to be sequenced completely. Using this approach we identified phosphatidylethanolamine-binding protein (PEBP) gene family members in sugarcane that are similar to the archetypical FT and TFL1 genes of Arabidopsis that play an essential role in controlling the transition from vegetative to reproductive growth. Expression analysis of ScTFL1, which falls into the TFL1-clade of floral repressors, showed transcripts in developing leaves surrounding the shoot apex but not at the apex itself. ScFT1 was detected in immature leaves and apical regions of vegetatively growing plants and, after the floral transition, expression also occurred in mature leaves. Ectopic over-expression of ScTFL1 in Arabidopsis caused delayed flowering in Arabidopsis, as might be expected for a gene related to TFL1. In addition, lines with the latest flowering phenotype exhibited aerial rosette formation. Unexpectedly, over-expression of ScFT1, which has greatest similarity to the florigen-encoding FT, also caused a delay in flowering. This preliminary analysis of divergent sugarcane FT and TFL1 gene family members from Saccharum spp. suggests that their expression patterns and roles in the floral transition has diverged from the predicted role of similar PEBP family members.

  5. Human Epidermal Growth Factor Receptor 2 Overexpression in Micropapillary and Other Variants of Urothelial Carcinoma.

    Science.gov (United States)

    Behzatoğlu, Kemal; Yörükoğlu, Kutsal; Demir, Hale; Bal, Nebil

    2016-06-21

    Human epidermal growth factor receptor 2 (HER2) protein overexpression or gene amplification has been shown in urothelial bladder cancer. This could be helpful when using targeted anti-HER2 therapy on these tumors. To evaluate HER2 immunohistochemical expression in conventional urothelial carcinoma (UC), in situ UC, and UC variants primarily in micropapillary urothelial carcinoma (MPUC). The study evaluated 60 MPUC cases; 25 invasive, 20 low-grade noninvasive, and 10 high-grade noninvasive UC cases; 8 in situ UC cases; and 69 UC variant cases. The immunohistochemistry staining was scored according to recommendations of the American Society of Clinical Oncology/College of American Pathologists 2013 HER2 test guideline established for breast cancer and only 3+ staining was considered HER2 overexpression. HER2 overexpression was determined by 3+ staining. 34 of 60 MPUC cases (56%) showed HER2 overexpression (3+ staining). We observed 3+ staining HER2 overexpression in nine of 25 conventional invasive UC cases (36%), four of eight in situ UC cases (50%), and three of six lipid cell variant cases (50%). 3+ staining HER2 overexpression was not seen in eight glandular, six small cell, and five sarcomatoid variant cases. HER2 overexpression was negative in the 20 low-grade noninvasive UC cases but positive in two of the 10 high-grade noninvasive UC cases (20%). We observed HER2 overexpression most commonly in MPUC cases. We also found HER2 overexpression in conventional invasive and in situ UC cases. Pure in situ UC and conventional invasive UC, especially MPUC, could be candidate tumors for treatment with anti-HER2 antibody (trastuzumab therapy). Targeted therapy has a limited place in treatment of bladder cancer. In this study, human epidermal growth factor receptor 2 (HER2) overexpression in bladder carcinomas was evaluated in a large number of cases. Anti-HER2 therapy could be used in bladder cancers, as in breast and gastric cancers. Copyright © 2016 European

  6. Facilitating tolerance of delayed reinforcement during functional communication training.

    Science.gov (United States)

    Fisher, W W; Thompson, R H; Hagopian, L P; Bowman, L G; Krug, A

    2000-01-01

    Few clinical investigations have addressed the problem of delayed reinforcement. In this investigation, three individuals whose destructive behavior was maintained by positive reinforcement were treated using functional communication training (FCT) with extinction (EXT). Next, procedures used in the basic literature on delayed reinforcement and self-control (reinforcer delay fading, punishment of impulsive responding, and provision of an alternative activity during reinforcer delay) were used to teach participants to tolerate delayed reinforcement. With the first case, reinforcer delay fading alone was effective at maintaining low rates of destructive behavior while introducing delayed reinforcement. In the second case, the addition of a punishment component reduced destructive behavior to near-zero levels and facilitated reinforcer delay fading. With the third case, reinforcer delay fading was associated with increases in masturbation and head rolling, but prompting and praising the individual for completing work during the delay interval reduced all problem behaviors and facilitated reinforcer delay fading.

  7. Delayed neutrons in liquid metal spallation targets

    International Nuclear Information System (INIS)

    Ridikas, D.; Bokov, P.; David, J.C.; Dore, D.; Giacri, M.L.; Van Lauwe, A.; Plukiene, R.; Plukis, A.; Ignatiev, S.; Pankratov, D.

    2003-01-01

    The next generation spallation neutron sources, neutrino factories or RIB production facilities currently being designed and constructed around the world will increase the average proton beam power on target by a few orders of magnitude. Increased proton beam power results in target thermal hydraulic issues leading to new target designs, very often based on flowing liquid metal targets such as Hg, Pb, Pb-Bi. Radioactive nuclides produced in liquid metal targets are transported into hot cells, past electronics, into pumps with radiation sensitive components, etc. Besides the considerable amount of photon activity in the irradiated liquid metal, a significant amount of the delayed neutron precursor activity can be accumulated in the target fluid. The transit time from the front of a liquid metal target into areas, where delayed neutrons may be important, can be as short as a few seconds, well within one half-life of many delayed neutron precursors. Therefore, it is necessary to evaluate the total neutron flux (including delayed neutrons) as a function of time and determine if delayed neutrons contribute significantly to the dose rate. In this study the multi-particle transport code MCNPX combined with the material evolution program CINDER'90 will be used to evaluate the delayed neutron flux and spectra. The following scientific issues will be addressed in this paper: - Modeling of a typical geometry of the liquid metal spallation target; - Predictions of the prompt neutron fluxes, fission fragment and spallation product distributions; - Comparison of the above parameters with existing experimental data; - Time-dependent calculations of delayed neutron precursors; - Neutron flux estimates due to the prompt and delayed neutron emission; - Proposal of an experimental program to measure delayed neutron spectra from high energy spallation-fission reactions. The results of this study should be directly applicable in the design study of the European MegaPie (1 MW

  8. Data Assimilation by delay-coordinate nudging

    Science.gov (United States)

    Pazo, Diego; Lopez, Juan Manuel; Carrassi, Alberto

    2016-04-01

    A new nudging method for data assimilation, delay-coordinate nudging, is presented. Delay-coordinate nudging makes explicit use of present and past observations in the formulation of the forcing driving the model evolution at each time-step. Numerical experiments with a low order chaotic system show that the new method systematically outperforms standard nudging in different model and observational scenarios, also when using an un-optimized formulation of the delay-nudging coefficients. A connection between the optimal delay and the dominant Lyapunov exponent of the dynamics is found based on heuristic arguments and is confirmed by the numerical results, providing a guideline for the practical implementation of the algorithm. Delay-coordinate nudging preserves the easiness of implementation, the intuitive functioning and the reduced computational cost of the standard nudging, making it a potential alternative especially in the field of seasonal-to-decadal predictions with large Earth system models that limit the use of more sophisticated data assimilation procedures.

  9. Television viewing associates with delayed language development.

    Science.gov (United States)

    Chonchaiya, Weerasak; Pruksananonda, Chandhita

    2008-07-01

    To identify impact of television viewing on language development. The case-control study included 56 new patients with language delay and 110 normal children, aged 15-48 months. Language delay was diagnosed by reviewing language milestones and Denver-II. Television viewing variables and child/parental characteristics between both groups were interviewed. The data were analyzed by ANOVA and chi-square test. Adjusted odds ratios and 95% confidence intervals were calculated from multivariate logistic regression model. Forty-six boys and 10 girls; mean [+/-SD] age, 2.11+/-0.47 years of the case group and 59 boys and 51 girls; mean [+/-SD] age, 2.23+/-0.80 years of the control group were enrolled. Children who had language delay usually started watching television earlier at age 7.22+/-5.52 months vs. 11.92+/-5.86 months, p-valuetelevision than normal children (3.05+/-1.90 h/day vs. 1.85+/-1.18 h/day; p-valuetelevision attelevision>2 h/day were approximately six times more likely to have language delays. There is a relationship between early onset and high frequency of TV viewing and language delay.

  10. Theory of attosecond delays in molecular photoionization.

    Science.gov (United States)

    Baykusheva, Denitsa; Wörner, Hans Jakob

    2017-03-28

    We present a theoretical formalism for the calculation of attosecond delays in molecular photoionization. It is shown how delays relevant to one-photon-ionization, also known as Eisenbud-Wigner-Smith delays, can be obtained from the complex dipole matrix elements provided by molecular quantum scattering theory. These results are used to derive formulae for the delays measured by two-photon attosecond interferometry based on an attosecond pulse train and a dressing femtosecond infrared pulse. These effective delays are first expressed in the molecular frame where maximal information about the molecular photoionization dynamics is available. The effects of averaging over the emission direction of the electron and the molecular orientation are introduced analytically. We illustrate this general formalism for the case of two polyatomic molecules. N 2 O serves as an example of a polar linear molecule characterized by complex photoionization dynamics resulting from the presence of molecular shape resonances. H 2 O illustrates the case of a non-linear molecule with comparably simple photoionization dynamics resulting from a flat continuum. Our theory establishes the foundation for interpreting measurements of the photoionization dynamics of all molecules by attosecond metrology.

  11. Time delay interferometry with moving spacecraft arrays

    International Nuclear Information System (INIS)

    Tinto, Massimo; Estabrook, F.B.; Armstrong, J.W.

    2004-01-01

    Space-borne interferometric gravitational wave detectors, sensitive in the low-frequency (millihertz) band, will fly in the next decade. In these detectors the spacecraft-to-spacecraft light-travel-times will necessarily be unequal, time varying, and (due to aberration) have different time delays on up and down links. The reduction of data from moving interferometric laser arrays in solar orbit will in fact encounter nonsymmetric up- and down-link light time differences that are about 100 times larger than has previously been recognized. The time-delay interferometry (TDI) technique uses knowledge of these delays to cancel the otherwise dominant laser phase noise and yields a variety of data combinations sensitive to gravitational waves. Under the assumption that the (different) up- and down-link time delays are constant, we derive the TDI expressions for those combinations that rely only on four interspacecraft phase measurements. We then turn to the general problem that encompasses time dependence of the light-travel times along the laser links. By introducing a set of noncommuting time-delay operators, we show that there exists a quite general procedure for deriving generalized TDI combinations that account for the effects of time dependence of the arms. By applying our approach we are able to re-derive the 'flex-free' expression for the unequal-arm Michelson combinations X 1 , and obtain the generalized expressions for the TDI combinations called relay, beacon, monitor, and symmetric Sagnac

  12. Investigation of delayed fission gas release

    International Nuclear Information System (INIS)

    Cayet, Nicolas

    1996-05-01

    The study of the fission gas release process in the high burnup rig IFA-562 has revealed a particular fuel behaviour: a delay in the fission gas release process. It appeared that an important release of gas was measured by the pressure transducers once the power had decreased, whereas, during steady-state operation, the pressure did not increase very much. After examinations, the gap size has been concluded to be the main parameter involving this delay. However the burnup could have been a potential factor, its role is mainly to close the gap by swelling. The observations of low burnup rods have shown the same delayed fission gas release, the gap being small by design and closed essentially by thermal expansion. The study of the kinetics has demonstrated the time-independency of the phenomenon. Thus the proposed mechanism driving this delayed fission gas release would involve three consecutives stages. During steady-state, the gas is released into the interlinkage network of grain boundary bubbles and cracks. Due to the closed gap, the gas is trapped in some void volumes, unable to escape the pellet. During power reduction, the gap and some old/new cracks open, immediately providing a path for the gas to the pressure transducers and explaining this delay in the fission gas release. (author)

  13. Communication key using delay times in time-delayed chaos synchronization

    International Nuclear Information System (INIS)

    Kim, Chil-Min; Kye, Won-Ho; Rim, Sunghwan; Lee, Soo-Young

    2004-01-01

    We propose an efficient key scheme, which can generate a great number of communication keys, for communication using chaos synchronization. We have attained the keys from delay times of time-delay coupled chaotic systems. We explain the scheme and the efficiency by coupling Henon and logistic maps and illustrate them by coupling Navier-Stokes and Lorenz equations as a continuous system

  14. PRAME overexpression predicted good outcome in pediatric B-cell acute lymphoblastic leukemia patients receiving chemotherapy.

    Science.gov (United States)

    Zhang, Yan-Huan; Lu, Ai-Dong; Yang, Lu; Li, Ling-Di; Chen, Wen-Min; Long, Ling-Yu; Zhang, Le-Ping; Qin, Ya-Zhen

    2017-01-01

    To investigate the prognostic value of PRAME expression in pediatric acute lymphoblastic leukemia(ALL), we measured PRAME transcript levels at diagnosis in 191 patients(146 B-ALL; 45T-ALL)receiving chemotherapy only. PRAME overexpression was defined as transcript levels higher than 0.30%, which is the upper limit of normal bone marrow and the optimal cutoff value derived from ROC curve analysis. PRAME overexpression was identified in 45.5% of patients. In B-ALL, PRAME overexpression was significantly associated with lower CIR(cumulative incidence of relapse), higher DFS (disease-freesurvival), and OS(overall survival) rates at 3 years, respectively (5.8% vs. 14.9%, P=0.014; 94.2% vs. 85.1%, P=0.014; 96.0% vs. 87.4%, P=0.039). PRAME overexpression had no impact on outcome in T-ALL patients. Among B-ALL patients with non-poor cytogenetic risk, those with PRAME overexpression showed significantly lower CIR, higher DFS and OS rates at 3 years, respectively (8.47% vs. 14.5%, P=0.009; 96.5% vs. 85.5%, P=0.009; 98.4% vs. 88.0%, P=0.023). Furthermore, PRAME overexpression was an independent good prognostic factor for relapse in all B-ALL patients and B-ALL patients with non-poor cytogenetic risk. Therefore, the prognostic significance of PRAME overexpression differed by ALL subtype; It predicted good outcome in pediatric B-ALL receiving chemotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Twinkle overexpression prevents cardiac rupture after myocardial infarction by alleviating impaired mitochondrial biogenesis.

    Science.gov (United States)

    Inoue, Takahiro; Ikeda, Masataka; Ide, Tomomi; Fujino, Takeo; Matsuo, Yuka; Arai, Shinobu; Saku, Keita; Sunagawa, Kenji

    2016-09-01

    Cardiac rupture is a fatal complication after myocardial infarction (MI). However, the detailed mechanism underlying cardiac rupture after MI remains to be fully elucidated. In this study, we investigated the role of mitochondrial DNA (mtDNA) and mitochondria in the pathophysiology of cardiac rupture by analyzing Twinkle helicase overexpression mice (TW mice). Twinkle overexpression increased mtDNA copy number approximately twofold and ameliorated ischemic cardiomyopathy at day 28 after MI. Notably, Twinkle overexpression markedly prevented cardiac rupture and improved post-MI survival, accompanied by the suppression of MMP-2 and MMP-9 in the MI border area at day 5 after MI when cardiac rupture frequently occurs. Additionally, these cardioprotective effects of Twinkle overexpression were abolished in transgenic mice overexpressing mutant Twinkle with an in-frame duplication of amino acids 353-365, which resulted in no increases in mtDNA copy number. Furthermore, although apoptosis and oxidative stress were induced and mitochondria were damaged in the border area, these injuries were improved in TW mice. Further analysis revealed that mitochondrial biogenesis, including mtDNA copy number, transcription, and translation, was severely impaired in the border area at day 5 In contrast, Twinkle overexpression maintained mtDNA copy number and restored the impaired transcription and translation of mtDNA in the border area. These results demonstrated that Twinkle overexpression alleviated impaired mitochondrial biogenesis in the border area through maintained mtDNA copy number and thereby prevented cardiac rupture accompanied by the reduction of apoptosis and oxidative stress, and suppression of MMP activity. Copyright © 2016 the American Physiological Society.

  16. Effects of GGCX overexpression on anterior cruciate ligament transection-induced osteoarthritis in rabbits.

    Science.gov (United States)

    Fu, Xiaoling; Qiu, Ruiyun; Tang, Chunfang; Wang, Xiaomei; Cheng, Xigao; Yin, Ming

    2018-03-01

    Effective therapeutic methods for osteoarthritis (OA) are lacking. γ‑glutamyl carboxylase (GGCX) is a key enzyme that regulates carboxylation of cartilage matrix Gla protein (MGP). Whether GGCX overexpression protects against OA remains unknown. The aim of the present study was to explore the effects of GGCX overexpression on anterior cruciate ligament transection (ACLT)‑induced OA and its mechanisms in Japanese white rabbits. ACLT surgery was used to establish an OA model in rabbits. A total of 48 rabbits were randomly divided into 4 groups: Sham, OA model + GGCX overexpression plasmid, OA model + saline and OA model + empty vector. The expression of uncarboxylated MGP (ucMGP), carboxylated MGP (cMGP), matrix metalloproteinase (MMP)‑13, collagen type X, collagen type II, tumor necrosis factor (TNF)‑α and interleukin (IL)‑1β were detected by ELISA, immunohistochemistry, reverse transcription‑quantitative polymerase chain reaction and western blotting. Morphological changes to tibial cartilage were assessed by Giemsa and safranin O‑fast green staining, respectively. Compared with the Sham control, GGCX expression was significantly decreased in the OA Model group. GGCX expression was increased by injection of a lentivirus‑carried overexpression plasmid that encoded GGCX. GGCX overexpression ameliorated ATLC‑induced damage in articular cartilage. OA Model rabbits exhibited significantly decreased expression levels of cMGP and collagen type II, and increased expression of ucMGP, collagen type X, MMP‑13, IL‑1β and TNF‑α. Notably, these expression levels were reversed by GGCX overexpression in OA Model rabbits. Results from the present study indicated that GGCX expression was decreased in OA Model rabbits, whereas overexpression of GGCX was able to promote carboxylation of MGP, reduce inflammation, decrease MMP‑13 expression and regulate collagen expression. The results also indicated that GGCX may serve as a therapeutic target for OA.

  17. Ameliorating replicative senescence of human bone marrow stromal cells by PSMB5 overexpression

    International Nuclear Information System (INIS)

    Lu, Li; Song, Hui-Fang; Wei, Jiao-Long; Liu, Xue-Qin; Song, Wen-Hui; Yan, Ba-Yi; Yang, Gui-Jiao; Li, Ang; Yang, Wu-Lin

    2014-01-01

    Highlights: • PSMB5 overexpression restores the differentiation potential of aged hBMSCs. • PSMB5 overexpression enhances the proteasomal activity of late-stage hBMSCs. • PSMB5 overexpression inhibits replicative senescence and improved cell viability. • PSMB5 overexpression promotes cell growth by upregulating the Cyclin D1/CDK4 complex. - Abstract: Multipotent human bone marrow stromal cells (hBMSCs) potentially serve as a source for cell-based therapy in regenerative medicine. However, in vitro expansion was inescapably accompanied with cell senescence, characterized by inhibited proliferation and compromised pluripotency. We have previously demonstrated that this aging process is closely associated with reduced 20S proteasomal activity, with down-regulation of rate-limiting catalytic β-subunits particularly evident. In the present study, we confirmed that proteasomal activity directly contributes to senescence of hBMSCs, which could be reversed by overexpression of the β5-subunit (PSMB5). Knocking down PSMB5 led to decreased proteasomal activity concurrent with reduced cell proliferation in early-stage hBMSCs, which is similar to the senescent phenotype observed in late-stage cells. In contrast, overexpressing PSMB5 in late-stage cells efficiently restored the normal activity of 20S proteasomes and promoted cell growth, possibly via upregulating the Cyclin D1/CDK4 complex. Additionally, PSMB5 could enhance cell resistance to oxidative stress, as evidenced by the increased cell survival upon exposing senescent hBMSCs to hydrogen peroxide. Furthermore, PSMB5 overexpression retained the pluripotency of late-stage hBMSCs by facilitating their neural differentiation both in vitro and in vivo. Collectively, our work reveals a critical role of PSMB5 in 20S proteasome-mediated protection against replicative senescence, pointing to a possible strategy for maintaining the integrity of culture-expanded hBMSCs by manipulating the expression of PSMB5

  18. Ameliorating replicative senescence of human bone marrow stromal cells by PSMB5 overexpression

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Li, E-mail: luli7300@126.com [Department of Anatomy, Shanxi Medical University, Taiyuan 030001 (China); Song, Hui-Fang; Wei, Jiao-Long; Liu, Xue-Qin [Department of Anatomy, Shanxi Medical University, Taiyuan 030001 (China); Song, Wen-Hui [Department of Orthopaedics, The Second Affiliated Hospital of Shanxi Medical University, Taiyuan 030001 (China); Yan, Ba-Yi; Yang, Gui-Jiao [Department of Anatomy, Shanxi Medical University, Taiyuan 030001 (China); Li, Ang [Department of Medicine, University of Hong Kong Faculty of Medicine, Hong Kong (Hong Kong); Department of Anatomy, University of Hong Kong Faculty of Medicine, Hong Kong (Hong Kong); Yang, Wu-Lin, E-mail: wulinyoung@163.com [School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei 230009 (China); Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium (SBIC), Agency for Science, Technology and Research - A*STAR (Singapore)

    2014-01-24

    Highlights: • PSMB5 overexpression restores the differentiation potential of aged hBMSCs. • PSMB5 overexpression enhances the proteasomal activity of late-stage hBMSCs. • PSMB5 overexpression inhibits replicative senescence and improved cell viability. • PSMB5 overexpression promotes cell growth by upregulating the Cyclin D1/CDK4 complex. - Abstract: Multipotent human bone marrow stromal cells (hBMSCs) potentially serve as a source for cell-based therapy in regenerative medicine. However, in vitro expansion was inescapably accompanied with cell senescence, characterized by inhibited proliferation and compromised pluripotency. We have previously demonstrated that this aging process is closely associated with reduced 20S proteasomal activity, with down-regulation of rate-limiting catalytic β-subunits particularly evident. In the present study, we confirmed that proteasomal activity directly contributes to senescence of hBMSCs, which could be reversed by overexpression of the β5-subunit (PSMB5). Knocking down PSMB5 led to decreased proteasomal activity concurrent with reduced cell proliferation in early-stage hBMSCs, which is similar to the senescent phenotype observed in late-stage cells. In contrast, overexpressing PSMB5 in late-stage cells efficiently restored the normal activity of 20S proteasomes and promoted cell growth, possibly via upregulating the Cyclin D1/CDK4 complex. Additionally, PSMB5 could enhance cell resistance to oxidative stress, as evidenced by the increased cell survival upon exposing senescent hBMSCs to hydrogen peroxide. Furthermore, PSMB5 overexpression retained the pluripotency of late-stage hBMSCs by facilitating their neural differentiation both in vitro and in vivo. Collectively, our work reveals a critical role of PSMB5 in 20S proteasome-mediated protection against replicative senescence, pointing to a possible strategy for maintaining the integrity of culture-expanded hBMSCs by manipulating the expression of PSMB5.

  19. A novel vector-based method for exclusive overexpression of star-form microRNAs.

    Directory of Open Access Journals (Sweden)

    Bo Qu

    Full Text Available The roles of microRNAs (miRNAs as important regulators of gene expression have been studied intensively. Although most of these investigations have involved the highly expressed form of the two mature miRNA species, increasing evidence points to essential roles for star-form microRNAs (miRNA*, which are usually expressed at much lower levels. Owing to the nature of miRNA biogenesis, it is challenging to use plasmids containing miRNA coding sequences for gain-of-function experiments concerning the roles of microRNA* species. Synthetic microRNA mimics could introduce specific miRNA* species into cells, but this transient overexpression system has many shortcomings. Here, we report that specific miRNA* species can be overexpressed by introducing artificially designed stem-loop sequences into short hairpin RNA (shRNA overexpression vectors. By our prototypic plasmid, designed to overexpress hsa-miR-146b-3p, we successfully expressed high levels of hsa-miR-146b-3p without detectable change of hsa-miR-146b-5p. Functional analysis involving luciferase reporter assays showed that, like natural miRNAs, the overexpressed hsa-miR-146b-3p inhibited target gene expression by 3'UTR seed pairing. Our demonstration that this method could overexpress two other miRNAs suggests that the approach should be broadly applicable. Our novel strategy opens the way for exclusively stable overexpression of miRNA* species and analyzing their unique functions both in vitro and in vivo.

  20. Time-delayed autosynchronous swarm control.

    Science.gov (United States)

    Biggs, James D; Bennet, Derek J; Dadzie, S Kokou

    2012-01-01

    In this paper a general Morse potential model of self-propelling particles is considered in the presence of a time-delayed term and a spring potential. It is shown that the emergent swarm behavior is dependent on the delay term and weights of the time-delayed function, which can be set to induce a stationary swarm, a rotating swarm with uniform translation, and a rotating swarm with a stationary center of mass. An analysis of the mean field equations shows that without a spring potential the motion of the center of mass is determined explicitly by a multivalued function. For a nonzero spring potential the swarm converges to a vortex formation about a stationary center of mass, except at discrete bifurcation points where the center of mass will periodically trace an ellipse. The analytical results defining the behavior of the center of mass are shown to correspond with the numerical swarm simulations.

  1. Positive mood effects on delay discounting.

    Science.gov (United States)

    Hirsh, Jacob B; Guindon, Alex; Morisano, Dominique; Peterson, Jordan B

    2010-10-01

    Delay discounting is the process by which the value of an expected reward decreases as the delay to obtaining that reward increases. Individuals with higher discounting rates tend to prefer smaller immediate rewards over larger delayed rewards. Previous research has indicated that personality can influence an individual's discounting rates, with higher levels of Extraversion predicting a preference for immediate gratification. The current study examined how this relationship would be influenced by situational mood inductions. While main effects were observed for both Extraversion and cognitive ability in the prediction of discounting rates, a significant interaction was also observed between Extraversion and positive affect. Extraverted individuals were more likely to prefer an immediate reward when first put in a positive mood. Extraverts thus appear particularly sensitive to impulsive, incentive-reward-driven behavior by temperament and by situational factors heightening positive affect. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

  2. Delays in the management of retroperitoneal sarcomas

    DEFF Research Database (Denmark)

    Seinen, Jojanneke; Almquist, Martin; Styring, Emelie

    2010-01-01

    Retroperitoneal sarcomas are rare and treatment should optimally be centralized. Despite successful centralization with 90% of the patients referred prior to surgery, delays occur, which led us to assess lead times in a population-based series. Method. Patients diagnosed with retroperitoneal...... sarcoma in the southern Sweden health care region 2003-2009 were eligible for the study. Data on referrals and diagnostic investigations were collected from clinical files from primary health care, local hospitals, and from the sarcoma centre. Lead times were divided into patient delays and health care...... at the general practitioner, 36 days at local hospitals, and 55 days at the sarcoma centre. Conclusion. Centralization per se is not sufficient for optimized and efficient management. Our findings suggest that delays can be minimized by direct referral of patients from primary health care to sarcoma centers...

  3. On stochastic differential equations with random delay

    International Nuclear Information System (INIS)

    Krapivsky, P L; Luck, J M; Mallick, K

    2011-01-01

    We consider stochastic dynamical systems defined by differential equations with a uniform random time delay. The latter equations are shown to be equivalent to deterministic higher-order differential equations: for an nth-order equation with random delay, the corresponding deterministic equation has order n + 1. We analyze various examples of dynamical systems of this kind, and find a number of unusual behaviors. For instance, for the harmonic oscillator with random delay, the energy grows as exp((3/2) t 2/3 ) in reduced units. We then investigate the effect of introducing a discrete time step ε. At variance with the continuous situation, the discrete random recursion relations thus obtained have intrinsic fluctuations. The crossover between the fluctuating discrete problem and the deterministic continuous one as ε goes to zero is studied in detail on the example of a first-order linear differential equation

  4. Delay time and tunneling transient phenomena

    International Nuclear Information System (INIS)

    Garcia-Calderon, Gaston; Villavicencio, Jorge

    2002-01-01

    Analytic solutions to the time-dependent Schroedinger equation for cutoff wave initial conditions are used to investigate the time evolution of the transmitted probability density for tunneling. For a broad range of values of the potential barrier opacity α, we find that the probability density exhibits two evolving structures. One refers to the propagation of a forerunner related to a time domain resonance [Phys. Rev. A 64, 0121907 (2001)], while the other consists of a semiclassical propagating wave front. We find a regime where the forerunners are absent, corresponding to positive time delays, and show that this regime is characterized by opacities α c . The critical opacity α c is derived from the analytical expression for the delay time, which reflects a link between transient effects in tunneling and the delay time

  5. Delayed switching applied to memristor neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Frank Z.; Yang Xiao; Lim Guan [Future Computing Group, School of Computing, University of Kent, Canterbury (United Kingdom); Helian Na [School of Computer Science, University of Hertfordshire, Hatfield (United Kingdom); Wu Sining [Xyratex, Havant (United Kingdom); Guo Yike [Department of Computing, Imperial College, London (United Kingdom); Rashid, Md Mamunur [CERN, Geneva (Switzerland)

    2012-04-01

    Magnetic flux and electric charge are linked in a memristor. We reported recently that a memristor has a peculiar effect in which the switching takes place with a time delay because a memristor possesses a certain inertia. This effect was named the ''delayed switching effect.'' In this work, we elaborate on the importance of delayed switching in a brain-like computer using memristor neural networks. The effect is used to control the switching of a memristor synapse between two neurons that fire together (the Hebbian rule). A theoretical formula is found, and the design is verified by a simulation. We have also built an experimental setup consisting of electronic memristive synapses and electronic neurons.

  6. Delayed switching applied to memristor neural networks

    International Nuclear Information System (INIS)

    Wang, Frank Z.; Yang Xiao; Lim Guan; Helian Na; Wu Sining; Guo Yike; Rashid, Md Mamunur

    2012-01-01

    Magnetic flux and electric charge are linked in a memristor. We reported recently that a memristor has a peculiar effect in which the switching takes place with a time delay because a memristor possesses a certain inertia. This effect was named the ''delayed switching effect.'' In this work, we elaborate on the importance of delayed switching in a brain-like computer using memristor neural networks. The effect is used to control the switching of a memristor synapse between two neurons that fire together (the Hebbian rule). A theoretical formula is found, and the design is verified by a simulation. We have also built an experimental setup consisting of electronic memristive synapses and electronic neurons.

  7. Delayed feedback control in quantum transport.

    Science.gov (United States)

    Emary, Clive

    2013-09-28

    Feedback control in quantum transport has been predicted to give rise to several interesting effects, among them quantum state stabilization and the realization of a mesoscopic Maxwell's daemon. These results were derived under the assumption that control operations on the system are affected instantaneously after the measurement of electronic jumps through it. In this contribution, I describe how to include a delay between detection and control operation in the master equation theory of feedback-controlled quantum transport. I investigate the consequences of delay for the state stabilization and Maxwell's daemon schemes. Furthermore, I describe how delay can be used as a tool to probe coherent oscillations of electrons within a transport system and how this formalism can be used to model finite detector bandwidth.

  8. Radiochemical Means of Investigating Delayed Neutron Precursors

    International Nuclear Information System (INIS)

    Marmol, P. del

    1968-01-01

    Fast radiochemical methods used now for the determination of delayed neutron precursors are classified and reviewed: precipitations, solvent extractions, range experiments, milking, gas sweeping, isotopic and ion exchange, hot atom reactions and diffusion loss. Advantages and limitations of irradiation systems with respect to fast separations are discussed: external beams which allow faster separations only have low neutron fluxes, internal beams which are mostly fit for gaseous reactions; and rabbits for solution irradiations. Future prospects of radiochemical procedures are presented; among these, studies should be mostly oriented towards gaseous reactions which offer possibilities of isolating very short-lived delayed neutron precursors. Chemical procedures for delayed neutron precursor detection are compared with mass spectrometric and isotope separator techniques; it is concluded that the methods are complementary. (author)

  9. Radiochemical Means of Investigating Delayed Neutron Precursors

    International Nuclear Information System (INIS)

    Marmol, P. del

    1968-01-01

    Fast radiochemical methods used now for the determination of delayed neutron precursors are classified and reviewed: precipitations, solvent extractions, range experiments, milking, gas sweeping, isotopic and ion exchange, hot-atom reactions and diffusion loss. Advantages and limitations of irradiation systems with respect to fast separations are discussed: external beams which allow faster separations only have low neutron fluxes, internal beams which are mostly fit for gaseous reactions; and rabbits for solution irradiations. Future prospects of radiochemical procedures are presented; among these, studies should be mostly oriented towards gaseous reactions which offer possibilities of isolating very short-lived delayed neutron precursors. Chemical procedures for delayed neutron precursor detection are compared with mass spectrometric and isotope-separator techniques; it is concluded that the methods are complementary. (author)

  10. Abdominal CT findings of delayed postoperative complications

    Energy Technology Data Exchange (ETDEWEB)

    Zissin, R.; Osadchy, A. [Sapir Medical Center, Dept. of Diagnostic Imaging, Kfar Saba (Israel)]. E-mail: zisinrivka@clalit.org.il; Gayer, G. [Assaf Harofe Medical Center, Dept. of Diagnostic Imaging, Zrifin (Israel)

    2007-10-15

    Despite progress in surgical techniques and modern medical treatment, postoperative complications occur not infrequently and vary according to type of surgery, clinical setting, and time elapsed since surgery. In general, they can be divided into early and delayed complications. Delayed postoperative complications can be classified as specific and nonspecific. The common nonspecific delayed complications are incisional hernia and postoperative bowel obstruction. Bowel obstruction can be further categorized as obstruction related to benign or neoplastic etiology, the latter occurring in oncology patients in whom the primary surgery was related to an underlying abdominal neoplasm. Gossypiboma is another, fortunately rare, postoperative complication. Specific complications appear after specific operations and include the following: Splenosis - following splenectomy. Retained gallstones and spilled gallstones - following cholecystectomy, mainly laparoscopic. Dropped appendicolith and stump appendicitis - following appendectomy, mainly laparoscopic. Obturation obstruction by a bezoar - following gastric surgery. Afferent loop syndrome (ALS) - following Bilroth II gastrectomy. (author)

  11. A delay fractioning approach to global synchronization of delayed complex networks with stochastic disturbances

    International Nuclear Information System (INIS)

    Wang Yao; Wang Zidong; Liang Jinling

    2008-01-01

    In this Letter, the synchronization problem is investigated for a class of stochastic complex networks with time delays. By utilizing a new Lyapunov functional form based on the idea of 'delay fractioning', we employ the stochastic analysis techniques and the properties of Kronecker product to establish delay-dependent synchronization criteria that guarantee the globally asymptotically mean-square synchronization of the addressed delayed networks with stochastic disturbances. These sufficient conditions, which are formulated in terms of linear matrix inequalities (LMIs), can be solved efficiently by the LMI toolbox in Matlab. The main results are proved to be much less conservative and the conservatism could be reduced further as the number of delay fractioning gets bigger. A simulation example is exploited to demonstrate the advantage and applicability of the proposed result

  12. Classic conditioning in aged rabbits: delay, trace, and long-delay conditioning.

    Science.gov (United States)

    Solomon, P R; Groccia-Ellison, M E

    1996-06-01

    Young (0.5 years) and aged (2+, 3+, and 4+ years) rabbits underwent acquisition of the classically conditioned nictitating membrane response in a delay (500-ms conditioned stimulus [CS], 400-ms interstimulus interval [ISI]), long-delay (1,000-ms CS, 900-ms ISI), or trace (500-ms CS, 400-ms stimulus-free period) paradigm. Collapsing across age groups, there is a general tendency for animals to acquire trace conditioning more slowly than delay conditioning. Collapsing across conditioning paradigms, there is a general tendency for aged animals to acquire more slowly than younger animals. Of greater significance, however, are the age differences in the different conditioning paradigms. In the delay and long-delay paradigms, significant conditioning deficits first appeared in the 4(+)-year-old group. In the trace conditioning paradigm, significant conditioning deficits became apparent in the 2(+)-year-old animals.

  13. Modeling of delays in PKPD: classical approaches and a tutorial for delay differential equations.

    Science.gov (United States)

    Koch, Gilbert; Krzyzanski, Wojciech; Pérez-Ruixo, Juan Jose; Schropp, Johannes

    2014-08-01

    In pharmacokinetics/pharmacodynamics (PKPD) the measured response is often delayed relative to drug administration, individuals in a population have a certain lifespan until they maturate or the change of biomarkers does not immediately affects the primary endpoint. The classical approach in PKPD is to apply transit compartment models (TCM) based on ordinary differential equations to handle such delays. However, an alternative approach to deal with delays are delay differential equations (DDE). DDEs feature additional flexibility and properties, realize more complex dynamics and can complementary be used together with TCMs. We introduce several delay based PKPD models and investigate mathematical properties of general DDE based models, which serve as subunits in order to build larger PKPD models. Finally, we review current PKPD software with respect to the implementation of DDEs for PKPD analysis.

  14. Information transfer via implicit encoding with delay time modulation in a time-delay system

    Energy Technology Data Exchange (ETDEWEB)

    Kye, Won-Ho, E-mail: whkye@kipo.go.kr [Korean Intellectual Property Office, Government Complex Daejeon Building 4, 189, Cheongsa-ro, Seo-gu, Daejeon 302-701 (Korea, Republic of)

    2012-08-20

    A new encoding scheme for information transfer with modulated delay time in a time-delay system is proposed. In the scheme, the message is implicitly encoded into the modulated delay time. The information transfer rate as a function of encoding redundancy in various noise scales is presented and it is analyzed that the implicit encoding scheme (IES) has stronger resistance against channel noise than the explicit encoding scheme (EES). In addition, its advantages in terms of secure communication and feasible applications are discussed. -- Highlights: ► We propose new encoding scheme with delay time modulation. ► The message is implicitly encoded with modulated delay time. ► The proposed scheme shows stronger resistance against channel noise.

  15. Delayed minocycline but not delayed mild hypothermia protects against embolic stroke

    Directory of Open Access Journals (Sweden)

    Noor Raza

    2002-04-01

    Full Text Available Abstract Background Inflammatory reactions occurring in the brain after ischemia may contribute to secondary damage. In the present study, effects of minocycline, an anti-inflammatory agent, alone or in combination with mild hypothermia on focal embolic cerebral ischemia have been examined. Methods Focal ischemic injury was induced by embolizing a preformed clot into the middle cerebral artery (MCA. Infarction volume was measured at 48 h after the injury. Mortality was also recorded. Results Delayed administration of minocycline alone or delayed minocycline plus delayed mild hypothermia reduced the infarction volume significantly. However, delayed mild hypothermia alone was not protective and delayed mild hypothermia in combination with minocycline did not show any additive effect. Conclusions These results suggest that minocycline is beneficial in focal ischemic brain injury, and the lack of the enhanced neuroprotection may be due to the brief exposure to hypothermia.

  16. Atmospheric Phase Delay in Sentinel SAR Interferometry

    Science.gov (United States)

    Krishnakumar, V.; Monserrat, O.; Crosetto, M.; Crippa, B.

    2018-04-01

    The repeat-pass Synthetic Aperture Radio Detection and Ranging (RADAR) Interferometry (InSAR) has been a widely used geodetic technique for observing the Earth's surface, especially for mapping the Earth's topography and deformations. However, InSAR measurements are prone to atmospheric errors. RADAR waves traverse the Earth's atmosphere twice and experience a delay due to atmospheric refraction. The two major layers of the atmosphere (troposphere and ionosphere) are mainly responsible for this delay in the propagating RADAR wave. Previous studies have shown that water vapour and clouds present in the troposphere and the Total Electron Content (TEC) of the ionosphere are responsible for the additional path delay in the RADAR wave. The tropospheric refractivity is mainly dependent on pressure, temperature and partial pressure of water vapour. The tropospheric refractivity leads to an increase in the observed range. These induced propagation delays affect the quality of phase measurement and introduce errors in the topography and deformation fields. The effect of this delay was studied on a differential interferogram (DInSAR). To calculate the amount of tropospheric delay occurred, the meteorological data collected from the Spanish Agencia Estatal de Meteorología (AEMET) and MODIS were used. The interferograms generated from Sentinel-1 carrying C-band Synthetic Aperture RADAR Single Look Complex (SLC) images acquired on the study area are used. The study area consists of different types of scatterers exhibiting different coherence. The existing Saastamoinen model was used to perform a quantitative evaluation of the phase changes caused by pressure, temperature and humidity of the troposphere during the study. Unless the phase values due to atmospheric disturbances are not corrected, it is difficult to obtain accurate measurements. Thus, the atmospheric error correction is essential for all practical applications of DInSAR to avoid inaccurate height and deformation

  17. ATMOSPHERIC PHASE DELAY IN SENTINEL SAR INTERFEROMETRY

    Directory of Open Access Journals (Sweden)

    V. Krishnakumar

    2018-04-01

    Full Text Available The repeat-pass Synthetic Aperture Radio Detection and Ranging (RADAR Interferometry (InSAR has been a widely used geodetic technique for observing the Earth’s surface, especially for mapping the Earth’s topography and deformations. However, InSAR measurements are prone to atmospheric errors. RADAR waves traverse the Earth’s atmosphere twice and experience a delay due to atmospheric refraction. The two major layers of the atmosphere (troposphere and ionosphere are mainly responsible for this delay in the propagating RADAR wave. Previous studies have shown that water vapour and clouds present in the troposphere and the Total Electron Content (TEC of the ionosphere are responsible for the additional path delay in the RADAR wave. The tropospheric refractivity is mainly dependent on pressure, temperature and partial pressure of water vapour. The tropospheric refractivity leads to an increase in the observed range. These induced propagation delays affect the quality of phase measurement and introduce errors in the topography and deformation fields. The effect of this delay was studied on a differential interferogram (DInSAR. To calculate the amount of tropospheric delay occurred, the meteorological data collected from the Spanish Agencia Estatal de Meteorología (AEMET and MODIS were used. The interferograms generated from Sentinel-1 carrying C-band Synthetic Aperture RADAR Single Look Complex (SLC images acquired on the study area are used. The study area consists of different types of scatterers exhibiting different coherence. The existing Saastamoinen model was used to perform a quantitative evaluation of the phase changes caused by pressure, temperature and humidity of the troposphere during the study. Unless the phase values due to atmospheric disturbances are not corrected, it is difficult to obtain accurate measurements. Thus, the atmospheric error correction is essential for all practical applications of DInSAR to avoid inaccurate

  18. Observations on early and delayed colostomy closure.

    Science.gov (United States)

    Tade, A O; Salami, B A; Ayoade, B A

    2011-06-01

    Traditional treatment of a variety of colorectal pathologies had included a diverting colostomy that was closed eight or more weeks later during a readmission. The aim of this retrospective study was to determine the outcomes of early colostomy closure and delayed colostomy closure in patients with temporary colostomies following traumatic and non-traumatic colorectal pathologies. In this study early colostomy closure was the closure of a colostomy within three weeks of its construction, while delayed colostomy closure referred to closure after 3 weeks. Complete records of the 37 adult patients who had temporary colostomy constructed and closed between Jan. 1997 December 2003 for various colorectal pathologies were studied. Fourteen patients had early colostomy closure while 23 had delayed closure. In the early colostomy closure group there were 10 men and 4 women. The mean age of the patients was 28yr with a range of 18-65yr. Colostomies were closed 9-18 days after initial colostomy construction. There was no mortality. Morbidity rate 28.6% (4 out of 14). There were two faecal fistulas (14.3%). Twenty-three patients had delayed colostomy closure 8 weeks to 18 months after initial colostomy construction. These were patients unfit for early surgery after initial colostomy construction because of carcinoma, significant weight loss, or sepsis. There was no mortality. Morbidity rate was 26.1%. There were 3 faecal fistulas (13.2%). Outcomes following early colostomy closure and delayed closure were comparable. Patients fit for surgery should have early closure whilst patients who may have compromised health should have delayed closure.

  19. The Strong Lensing Time Delay Challenge (2014)

    Science.gov (United States)

    Liao, Kai; Dobler, G.; Fassnacht, C. D.; Treu, T.; Marshall, P. J.; Rumbaugh, N.; Linder, E.; Hojjati, A.

    2014-01-01

    Time delays between multiple images in strong lensing systems are a powerful probe of cosmology. At the moment the application of this technique is limited by the number of lensed quasars with measured time delays. However, the number of such systems is expected to increase dramatically in the next few years. Hundred such systems are expected within this decade, while the Large Synoptic Survey Telescope (LSST) is expected to deliver of order 1000 time delays in the 2020 decade. In order to exploit this bounty of lenses we needed to make sure the time delay determination algorithms have sufficiently high precision and accuracy. As a first step to test current algorithms and identify potential areas for improvement we have started a "Time Delay Challenge" (TDC). An "evil" team has created realistic simulated light curves, to be analyzed blindly by "good" teams. The challenge is open to all interested parties. The initial challenge consists of two steps (TDC0 and TDC1). TDC0 consists of a small number of datasets to be used as a training template. The non-mandatory deadline is December 1 2013. The "good" teams that complete TDC0 will be given access to TDC1. TDC1 consists of thousands of lightcurves, a number sufficient to test precision and accuracy at the subpercent level, necessary for time-delay cosmography. The deadline for responding to TDC1 is July 1 2014. Submissions will be analyzed and compared in terms of predefined metrics to establish the goodness-of-fit, efficiency, precision and accuracy of current algorithms. This poster describes the challenge in detail and gives instructions for participation.

  20. The delayed neutron method of uranium analysis

    International Nuclear Information System (INIS)

    Wall, T.

    1989-01-01

    The technique of delayed neutron analysis (DNA) is discussed. The DNA rig installed on the MOATA reactor, the assay standards and the types of samples which have been assayed are described. Of the total sample throughput of about 55,000 units since the uranium analysis service began, some 78% has been concerned with analysis of uranium ore samples derived from mining and exploration. Delayed neutron analysis provides a high sensitivity, low cost uranium analysis method for both uranium exploration and other applications. It is particularly suitable for analysis of large batch samples and for non-destructive analysis over a wide range of matrices. 8 refs., 4 figs., 3 tabs

  1. Time-delay analyzer with continuous discretization

    International Nuclear Information System (INIS)

    Bayatyan, G.L.; Darbinyan, K.T.; Mkrtchyan, K.K.; Stepanyan, S.S.

    1988-01-01

    A time-delay analyzer is described which when triggered by a start pulse of adjustable duration performs continuous discretization of the analyzed signal within nearly 22 ns time intervals, the recording in a memory unit with following slow read-out of the information to the computer and its processing. The time-delay analyzer consists of four CAMAC-VECTOR systems of unit width. With its help one can separate comparatively short, small-amplitude rare signals against the background of quasistationary noise processes. 4 refs.; 3 figs

  2. Delay line MWPC hazard signals inspector

    International Nuclear Information System (INIS)

    Turner, D.B.; Kirsten, F.; Guiragossian, Z.G.T.; Schilling, R.

    1976-01-01

    The Hazard Inspector is a CAMAC module which divides a MWPC delay line into 8 independent signal monitor and control segments. Independent control effectively reduces delay line occupation time and cuts the number of background and non-trigger particles accepted by the 4XQT charge-time-pulse-width digitizer, a device presented in a separate communication. Only segments containing legitimate information are digitized. Non-trigger related events are gated out at the digitizer, and contaminating hits are noted for computer correction

  3. Permanent molars: Delayed development and eruption

    Directory of Open Access Journals (Sweden)

    Arathi R

    2006-05-01

    Full Text Available Delayed development and eruption of all the permanent molars is a rare phenomenon, which can cause disturbance in the developing occlusion. The eruption of permanent first and second molars is very important for the coordination of facial growth and for providing sufficient occlusal support for undisturbed mastication. In the case described, the first permanent molars were delayed in their development and were seen erupting at the age of nine and a half years. Severe disparity between the left and the right side of the dentition with respect to the rate of development of molars were also present.

  4. Management of delayed nuclear power plant projects

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-09-01

    According to the available information at the IAEA PRIS (Power Reactor Information System) at the end of 1998 there were more than 40 nuclear power plant projects with delays of five or more years with respect to the originally scheduled commercial operation. The degree of conformance with original construction schedules showed large variations due to several issues, including financial, economic and public opinion factors. Taking into account the number of projects with several years delay in their original schedules, it was considered useful to identify the subject areas where exchange of experience among Member States would be mutually beneficial in identification of problems and development of guidance for successful management of the completion of these delayed projects. A joint programme of the IAEA Departments of Nuclear Energy (Nuclear Power Engineering Section) and Technical Co-operation (Europe Section, with additional support from the Latin America and West Asia Sections) was set up during the period 1997-1998. The specific aim of the programme was to provide assistance in the management of delayed nuclear power plants regarding measures to maintain readiness for resuming the project implementation schedule when the conditions permit. The integration of IAEA interdepartmental resources enabled the participation of 53 experts from 14 Member States resulting in a wider exchange of experience and dissemination of guidance. Under the framework of the joint programme, senior managers directly responsible for delayed nuclear power plant projects identified several issues or problem areas that needed to be addressed and guidance on management be provided. A work plan for the development of several working documents, addressing the different issues, was established. Subsequently these documents were merged into a single one to produce the present publication. This publication provides information and practical examples on necessary management actions to preserve

  5. Management of delayed nuclear power plant projects

    International Nuclear Information System (INIS)

    1999-09-01

    According to the available information at the IAEA PRIS (Power Reactor Information System) at the end of 1998 there were more than 40 nuclear power plant projects with delays of five or more years with respect to the originally scheduled commercial operation. The degree of conformance with original construction schedules showed large variations due to several issues, including financial, economic and public opinion factors. Taking into account the number of projects with several years delay in their original schedules, it was considered useful to identify the subject areas where exchange of experience among Member States would be mutually beneficial in identification of problems and development of guidance for successful management of the completion of these delayed projects. A joint programme of the IAEA Departments of Nuclear Energy (Nuclear Power Engineering Section) and Technical Co-operation (Europe Section, with additional support from the Latin America and West Asia Sections) was set up during the period 1997-1998. The specific aim of the programme was to provide assistance in the management of delayed nuclear power plants regarding measures to maintain readiness for resuming the project implementation schedule when the conditions permit. The integration of IAEA interdepartmental resources enabled the participation of 53 experts from 14 Member States resulting in a wider exchange of experience and dissemination of guidance. Under the framework of the joint programme, senior managers directly responsible for delayed nuclear power plant projects identified several issues or problem areas that needed to be addressed and guidance on management be provided. A work plan for the development of several working documents, addressing the different issues, was established. Subsequently these documents were merged into a single one to produce the present publication. This publication provides information and practical examples on necessary management actions to preserve

  6. Delay generation methods with reduced memory requirements

    DEFF Research Database (Denmark)

    Tomov, Borislav Gueorguiev; Jensen, Jørgen Arendt

    2003-01-01

    Modern diagnostic ultrasound beamformers require delay information for each sample along the image lines. In order to avoid storing large amounts of focusing data, delay generation techniques have to be used. In connection with developing a compact beamformer architecture, recursive algorithms were......) For the best parametric approach, the gate count was 2095, the maximum operation speed was 131.9 MHz, the power consumption at 40 MHz was 10.6 mW, and it requires 4 12-bit words for each image line and channel. 2) For the piecewise-linear approximation, the corresponding numbers are 1125 gates, 184.9 MHz, 7...

  7. The Consequences of Delaying Entrance into University

    DEFF Research Database (Denmark)

    Foley, Kelly; Groes, Fane

    Because the returns to education depend on the nite horizon of individuals' working lives, human capital models predict that if an individual is going to attend university, she should do so as soon as possible. Delaying university can also mean individuals have fewer years in which to accumulate...... post-schooling experience. In this paper, we use Danish administrative data to estimate the wage losses experienced by individuals who accumulate less post-schooling experience because they postponed entry into university following high school. All else equal, experience-related costs of delaying...

  8. Double Hopf bifurcation in delay differential equations

    Directory of Open Access Journals (Sweden)

    Redouane Qesmi

    2014-07-01

    Full Text Available The paper addresses the computation of elements of double Hopf bifurcation for retarded functional differential equations (FDEs with parameters. We present an efficient method for computing, simultaneously, the coefficients of center manifolds and normal forms, in terms of the original FDEs, associated with the double Hopf singularity up to an arbitrary order. Finally, we apply our results to a nonlinear model with periodic delay. This shows the applicability of the methodology in the study of delay models arising in either natural or technological problems.

  9. 4-channel time delayed pulse generator

    International Nuclear Information System (INIS)

    Wetzel, L.F.S.; Rossi, J.O.; Del Bosco, E.

    1987-02-01

    It is described the project of a 4-channel delayed pulse generator employed to trigger the plasma centrifuge experiment of the Laboratorio Associado de Plasmas. The circuit delivers pulses with amplitude of 15V, full width at half maximum of 50μs and rise time of 0.7μs. The maximum time delay is 100ms. There are two channels with a fine adjustment of 0-1ms. The system can be manually or automatically driven. (author) [pt

  10. Diagnosis delay in Libyan female breast cancer.

    Science.gov (United States)

    Ermiah, Eramah; Abdalla, Fathi; Buhmeida, Abdelbaset; Larbesh, Entesar; Pyrhönen, Seppo; Collan, Yrjö

    2012-08-21

    To study the diagnosis delay and its impact on stage of disease among women with breast cancer on Libya. 200 women, aged 22 to 75 years with breast cancer diagnosed during 2008-2009 were interviewed about the period from the first symptoms to the final histological diagnosis of breast cancer. This period (diagnosis time) was categorized into 3 periods: 6 months. If diagnosis time was longer than 3 months, the diagnosis was considered delayed (diagnosis delay). Consultation time was the time taken to visit the general practitioner after the first symptoms. Retrospective preclinical and clinical data were collected on a form (questionnaire) during an interview with each patient and from medical records. The median of diagnosis time was 7.5 months. Only 30.0% of patients were diagnosed within 3 months after symptoms. 14% of patients were diagnosed within 3-6 months and 56% within a period longer than 6 months. A number of factors predicted diagnosis delay: Symptoms were not considered serious in 27% of patients. Alternative therapy (therapy not associated with cancer) was applied in 13.0% of the patients. Fear and shame prevented the visit to the doctor in 10% and 4.5% of patients, respectively. Inappropriate reassurance that the lump was benign was an important reason for prolongation of the diagnosis time. Diagnosis delay was associated with initial breast symptom(s) that did not include a lump (p diagnosis, the clinical stage distribution was as follows: 9.0% stage I, 25.5% stage II, 54.0% stage III and 11.5% stage IV.Diagnosis delay was associated with bigger tumour size (p Diagnosis delay is very serious problem in Libya. Diagnosis delay was associated with complex interactions between several factors and with advanced stages. There is a need for improving breast cancer awareness and training of general practitioners to reduce breast cancer mortality by promoting early detection. The treatment guidelines should pay more attention to the early phases of breast

  11. Delayed dermal burns caused by dimethyl acetylenedicarboxylate

    Energy Technology Data Exchange (ETDEWEB)

    Slovak, A J; Payne, A R

    1984-07-01

    A chemical operator handling dimethyl acetylenedicarboxylate (DMAD) developed delayed and pain-free burns on one of his feet 2 days after a supposed spillage of DMAD. The injuries were confirmed to be associated with DMAD by chemical analysis of the operator's safety boot and patch tests. DMAD easily penetrates some protective clothing and dilute solutions can still be hazardous: the toxic effect is compounded by being delayed and painless. The lachrymatory irritant properties of undiluted DMAD are not adequate warning of its presence or spillage in quantities sufficient to cause significant skin damage.

  12. Causal Analysis of Railway Running Delays

    DEFF Research Database (Denmark)

    Cerreto, Fabrizio; Nielsen, Otto Anker; Harrod, Steven

    Operating delays and network propagation are inherent characteristics of railway operations. These are traditionally reduced by provision of time supplements or “slack” in railway timetables and operating plans. Supplement allocation policies must trade off reliability in the service commitments...... Denmark (the Danish infrastructure manager). The statistical analysis of the data identifies the minimum running times and the scheduled running time supplements and investigates the evolution of train delays along given train paths. An improved allocation of time supplements would result in smaller...

  13. Congenital rubella syndrome and delayed manifestations

    DEFF Research Database (Denmark)

    Dammeyer, Jesper Herup

    2010-01-01

    Objective: Several hypotheses of different medical and psychological delayed manifestations among people who have congenital rubella syndrome (CRS) have been discussed. This study tests some of these hypotheses of delayed manifestations. Methods: Gathering information about 35 individuals who hav...... which people with CRS face must primarily be understood in relation to congenital deafblindness and dual sensory and communicative deprivation....... CRS and who are congenitally deafblind. Results: None of the hypotheses could be confirmed when individuals with CRS were compared to a control group of individuals who were congenital deafblind with different aetiology than CRS. Conclusions: This study concludes that those health related problems...

  14. Simulation of activation and propagation delay during tripolar neural stimulation

    NARCIS (Netherlands)

    Goodall, E.V.; Goodall, Eleanor V.; Kosterman, L. Martin; Struijk, Johannes J.; Struijk, J.J.; Holsheimer, J.

    1993-01-01

    Computer simulations were perfonned to investigate the influence of stimulus amplitude on cathodal activation delay, propagation delay and blocking during stimulation with a bipolar cuff electrode. Activation and propagation delays were combined in a total delay term which was minimized between the

  15. Immunohistochemical determination of HER-2/neu overexpression in malignant melanoma reveals no prognostic value, while c-Kit (CD117 overexpression exhibits potential therapeutic implications

    Directory of Open Access Journals (Sweden)

    Potti Anil

    2003-01-01

    Full Text Available Abstract Background HER-2/neu and c-kit (CD117 onco-protein are increasingly being recognized as targets for therapy in solid tumors, but data on their role in malignant melanoma is currently limited. We studied the prevalence of overexpression of HER-2/neu and c-Kit in 202 patients with malignant melanoma to evaluate a possible prognostic value of these molecular targets in malignant melanoma. Methods Overexpression of HER-2/neu and c-Kit was evaluated using immunohistochemical assays in 202 archival tissue specimens. Results Between 1991 and 2001, 202 subjects (109 males; 54% and 93 females; 46% with malignant melanoma were studied with a mean age of 57 years (age range: 15–101 years. The most common histologic type was amelanotic melanoma (n = 62; 30.7% followed by superficial spreading melanoma (n = 54; 26.7%. The depth of penetration of melanoma (Breslow thickness, pT Stage ranged from 0.4 mm (stage pT1 to 8.0 mm (stage pT4A. Mean thickness was 2.6 mm (stage pT3A. The ECOG performance scores ranged from 0 to 3. Only 2 patients (0.9% revealed HER-2/neu overexpression, whereas 46 (22.8% revealed c-Kit overexpression. Multivariate analysis performed did not show a significant difference in survival between c-Kit positive and negative groups (p = 0.36. Interestingly, not only was c-Kit more likely to be overexpressed in the superficial spreading type, a preliminary association between the presence or absence of c-Kit overexpression and the existence of another second primary tumor was also observed. Conclusions The results of our large study indicate that the HER-2/neu onco-protein neither has a role in melanogenesis nor is a potential target for clinical trials with monoclonal antibody therapy. This indicates there is no role for its testing in patients with malignant melanoma. Although c-Kit, expressed preferentially in the superficial spreading type, may not have prognostic value, it does have significant therapeutic implications as a

  16. Clinical Implications of the Epidermal Growth Factor Receptor overexpression in the High-grade Astrocytomas

    International Nuclear Information System (INIS)

    Hong, Seong Eon; Kang, Jin Oh; Lee, Hye Kyoung; Yang, Moon Ho; Leem, Won; Cho, Kyung Sam

    1996-01-01

    To determine the incidence and prognostic effects of EGFR overexpression in the high-grade astrocytomas. With 23 paraffin blocks of the high-garde astrocytomas, expression of EGFR were evaluated by immunohistochemical staining employing polyclonal antibody raised to short cytoplasmic domain of the molecule. Two out of 7 anaplastic astrocytomas and 9 out of 16 glioblastoma multiform patients showed overexpression of EGFR(p=0.44). Three out of 11 patients of age below 55 and 8 out of 12 patients of age over 54 showed EGFR overexpression(p=0.141). Median survival of the EGFR negative anaplastic astrocytoma patient was 37 months. Median survival of the glioblastoma multiform patients were 11 months in EGFR negative group and 7 months in EGFR positive group. But survival difference was not significant(p=0.17). There was a marked trend of increasing overexpression of EGFR in older patients. But survival of the glioblastoma multiform decreased by the overexpression of the EGFR without significant

  17. Hyaluronan synthase 3 (HAS3) overexpression downregulates MV3 melanoma cell proliferation, migration and adhesion

    International Nuclear Information System (INIS)

    Takabe, Piia; Bart, Geneviève; Ropponen, Antti; Rilla, Kirsi; Tammi, Markku; Tammi, Raija; Pasonen-Seppänen, Sanna

    2015-01-01

    Malignant skin melanoma is one of the most deadly human cancers. Extracellular matrix (ECM) influences the growth of malignant tumors by modulating tumor cells adhesion and migration. Hyaluronan is an essential component of the ECM, and its amount is altered in many tumors, suggesting an important role for hyaluronan in tumorigenesis. Nonetheless its role in melanomagenesis is not understood. In this study we produced a MV3 melanoma cell line with inducible expression of the hyaluronan synthase 3 (HAS3) and studied its effect on the behavior of the melanoma cells. HAS3 overexpression expanded the cell surface hyaluronan coat and decreased melanoma cell adhesion, migration and proliferation by cell cycle arrest at G1/G0. Melanoma cell migration was restored by removal of cell surface hyaluronan by Streptomyces hyaluronidase and by receptor blocking with hyaluronan oligosaccharides, while the effect on cell proliferation was receptor independent. Overexpression of HAS3 decreased ERK1/2 phosphorylation suggesting that inhibition of MAP-kinase signaling was responsible for these suppressive effects on the malignant phenotype of MV3 melanoma cells. - Highlights: • Inducible HAS3-MV3 melanoma cell line was generated using Lentiviral transduction. • HAS3 overexpression inhibits MV3 cell migration via hyaluronan–receptor interaction. • HAS3 overexpression decreases MV3 melanoma cell proliferation and adhesion. • ERK1/2 phosphorylation is downregulated by 50% in HAS3 overexpressing cells. • The results suggest that hyaluronan has anti-cancer like effects in melanoma

  18. Bcl-2 overexpression prevents 99mTc-MIBI uptake in breast cancer cell lines

    International Nuclear Information System (INIS)

    Aloj, Luigi; Zannetti, Antonella; Caraco, Corradina; Del Vecchio, Silvana; Salvatore, Marco

    2004-01-01

    We have previously shown a correlation between the absence of technetium-99m methoxyisobutylisonitrile ( 99m Tc-MIBI) uptake and overexpression of the anti-apoptotic protein Bcl-2 in human breast carcinoma. To establish a direct cause-effect relationship between Bcl-2 overexpression and reduced 99m Tc-MIBI uptake, MCF-7 and T47D breast cancer cell lines were stably transfected with the human Bcl-2 gene to increase intracellular protein levels and tested for 99m Tc-MIBI uptake. All clones overexpressing Bcl-2 showed a dramatic reduction of 99m Tc-MIBI uptake as compared with mock transfected control cells. Tracer uptake was promptly and partially restored by induction of apoptosis with staurosporine treatment. After 4.5 h of staurosporine treatment, a tenfold increase in 99m Tc-MIBI uptake was observed in treated as compared with untreated Bcl-2 overexpressing cells. Our findings provide a rational basis for the development of an in vivo test to detect Bcl-2 overexpression in human tumours. (orig.)

  19. Overexpression of BIRC6 Is a Predictor of Prognosis for Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Tingting Hu

    Full Text Available Inhibitors of apoptosis proteins (IAPs have been well investigated in human cancers, where they are frequently overexpressed and associated with poor prognosis. Here we explored the role of baculoviral IAP repeat containing 6 (BIRC6, a member of IAPs, in human colorectal cancer (CRC.We used Western blotting and immunohistochemistry to examine BIRC6 expression in 7 CRC cell lines and 126 CRC clinical samples. We determined the biological significance of BIRC6 in CRC cell lines by a lentivirus-mediated silencing method.We reported that BIRC6 was overexpressed in CRC cell lines and clinical CRC tissues. BIRC6 overexpression was correlated with tumor size and invasion depth of CRC. BIRC6 overexpression is associated with worse overall survival (OS (P = 0.001 and shorter disease-free survival (DFS (P = 0.010. BIRC6 knockdown inhibited cell proliferation, arrested cell cycle at S phase, downregulated cyclin A2, B1, D1 and E1 levels, and sensitized CRC cells to chemotherapy in vitro and in vivo.Taken together, these data suggests that BIRC6 overexpression is a predictor of poor prognosis in colorectal cancer and BIRC6 could be a potential target of CRC therapy.

  20. Overexpressed Genes/ESTs and Characterization of Distinct Amplicons on 17823 in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ayse E. Erson

    2001-01-01

    Full Text Available 17823 is a frequent site of gene amplification in breast cancer. Several lines of evidence suggest the presence of multiple amplicons on 17823. To characterize distinct amplicons on 17823 and localize putative oncogenes, we screened genes and expressed sequence tags (ESTs in existing physical and radiation hybrid maps for amplification and overexpression in breast cancer cell lines by semiquantitative duplex PCR, semiquantitative duplex RT-PCR, Southern blot, Northern blot analyses. We identified two distinct amplicons on 17823, one including TBX2 and another proximal region including RPS6KB1 (PS6K and MUL. In addition to these previously reported overexpressed genes, we also identified amplification and overexpression of additional uncharacterized genes and ESTs, some of which suggest potential oncogenic activity. In conclusion, we have further defined two distinct regions of gene amplification and overexpression on 17823 with identification of new potential oncogene candidates. Based on the amplification and overexpression patterns of known and as of yet unrecognized genes on 17823, it is likely that some of these genes mapping to the discrete amplicons function as oncogenes and contribute to tumor progression in breast cancer cells.

  1. Hepatic NPC1L1 overexpression ameliorates glucose metabolism in diabetic mice via suppression of gluconeogenesis.

    Science.gov (United States)

    Kurano, Makoto; Hara, Masumi; Satoh, Hiroaki; Tsukamoto, Kazuhisa

    2015-05-01

    Inhibition of intestinal NPC1L1 by ezetimibe has been demonstrated to improve glucose metabolism in rodent models; however, the role of hepatic NPC1L1 in glucose metabolism has not been elucidated. In this study, we analyzed the effects of hepatic NPC1L1 on glucose metabolism. We overexpressed NPC1L1 in the livers of lean wild type mice, diet-induced obesity mice and db/db mice with adenoviral gene transfer. We found that in all three mouse models, hepatic NPC1L1 overexpression lowered fasting blood glucose levels as well as blood glucose levels on ad libitum; in db/db mice, hepatic NPC1L1 overexpression improved blood glucose levels to almost the same as those found in lean wild type mice. A pyruvate tolerance test revealed that gluconeogenesis was suppressed by hepatic NPC1L1 overexpression. Further analyses revealed that hepatic NPC1L1 overexpression decreased the expression of FoxO1, resulting in the reduced expression of G6Pase and PEPCK, key enzymes in gluconeogenesis. These results indicate that hepatic NPC1L1 might have distinct properties of suppressing gluconeogenesis via inhibition of FoxO1 pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Hyaluronan synthase 3 (HAS3) overexpression downregulates MV3 melanoma cell proliferation, migration and adhesion

    Energy Technology Data Exchange (ETDEWEB)

    Takabe, Piia, E-mail: piia.takabe@uef.fi [University of Eastern Finland, Institute of Biomedicine, 70211 Kuopio (Finland); Bart, Geneviève [University of Eastern Finland, Institute of Biomedicine, 70211 Kuopio (Finland); Ropponen, Antti [University of Eastern Finland, Institute of Clinical Medicine, 70211 Kuopio (Finland); Rilla, Kirsi; Tammi, Markku; Tammi, Raija; Pasonen-Seppänen, Sanna [University of Eastern Finland, Institute of Biomedicine, 70211 Kuopio (Finland)

    2015-09-10

    Malignant skin melanoma is one of the most deadly human cancers. Extracellular matrix (ECM) influences the growth of malignant tumors by modulating tumor cells adhesion and migration. Hyaluronan is an essential component of the ECM, and its amount is altered in many tumors, suggesting an important role for hyaluronan in tumorigenesis. Nonetheless its role in melanomagenesis is not understood. In this study we produced a MV3 melanoma cell line with inducible expression of the hyaluronan synthase 3 (HAS3) and studied its effect on the behavior of the melanoma cells. HAS3 overexpression expanded the cell surface hyaluronan coat and decreased melanoma cell adhesion, migration and proliferation by cell cycle arrest at G1/G0. Melanoma cell migration was restored by removal of cell surface hyaluronan by Streptomyces hyaluronidase and by receptor blocking with hyaluronan oligosaccharides, while the effect on cell proliferation was receptor independent. Overexpression of HAS3 decreased ERK1/2 phosphorylation suggesting that inhibition of MAP-kinase signaling was responsible for these suppressive effects on the malignant phenotype of MV3 melanoma cells. - Highlights: • Inducible HAS3-MV3 melanoma cell line was generated using Lentiviral transduction. • HAS3 overexpression inhibits MV3 cell migration via hyaluronan–receptor interaction. • HAS3 overexpression decreases MV3 melanoma cell proliferation and adhesion. • ERK1/2 phosphorylation is downregulated by 50% in HAS3 overexpressing cells. • The results suggest that hyaluronan has anti-cancer like effects in melanoma.

  3. Overexpression of AIB1 in nasopharyngeal carcinomas correlates closely with advanced tumor stage.

    Science.gov (United States)

    Liu, Meng-Zhong; Xie, Dan; Mai, Shi-Juan; Tong, Zhu-Ting; Shao, Jian-Yong; Fu, Yong-Shui; Xia, Wen-Jie; Kung, Hsian-Fu; Guan, Xin-Yuan; Zeng, Yi-Xin

    2008-05-01

    AIB1, a candidate oncogene in breast cancer, is commonly amplified and overexpressed in several types of human cancers. In this study, expression and amplification of AIB1 in nasopharyngeal carcinoma (NPC) were studied by immunohistochemical analysis and fluorescence in situ hybridization using tissue microarrays, including 80 specimens of NPC and 20 specimens of nonneoplastic nasopharyngeal mucosa. In this NPC cohort, overexpression and amplification of AIB1 was detected in 36 (51%) of 71 and 3 (7%) of 46 NPCs, respectively. Overexpression of AIB1 was observed more frequently in NPCs in late T stages (T3/T4, 24/35 [69%]) than in earlier stages (T1/T2, 12/36 [33%]; P < .05). In addition, 18 (72%) of 25 NPCs with lymph node metastasis (N1-3) showed overexpression of AIB1; the frequency was significantly higher than that in NPCs without node metastasis (N0, 18/49 [39%]; P < .05). These findings suggest that overexpression of AIB1 in NPCs may be important in the acquisition of an invasive and/or metastatic phenotype.

  4. Overexpression of Glucocorticoid Receptor β Enhances Myogenesis and Reduces Catabolic Gene Expression.

    Science.gov (United States)

    Hinds, Terry D; Peck, Bailey; Shek, Evan; Stroup, Steven; Hinson, Jennifer; Arthur, Susan; Marino, Joseph S

    2016-02-11

    Unlike the glucocorticoid receptor α (GRα), GR β (GRβ) has a truncated ligand-binding domain that prevents glucocorticoid binding, implicating GRα as the mediator of glucocorticoid-induced skeletal muscle loss. Because GRβ causes glucocorticoid resistance, targeting GRβ may be beneficial in impairing muscle loss as a result of GRα activity. The purpose of this study was to determine how the overexpression of GRβ affects myotube formation and dexamethasone (Dex) responsiveness. We measured GR isoform expression in C₂C12 muscle cells in response to Dex and insulin, and through four days of myotube formation. Next, lentiviral-mediated overexpression of GRβ in C₂C12 was performed, and these cells were characterized for cell fusion and myotube formation, as well as sensitivity to Dex via the expression of ubiquitin ligases. GRβ overexpression increased mRNA levels of muscle regulatory factors and enhanced proliferation in myoblasts. GRβ overexpressing myotubes had an increased fusion index. Myotubes overexpressing GRβ had lower forkhead box O3 (Foxo3a) mRNA levels and a blunted muscle atrophy F-box/Atrogen-1 (MAFbx) and muscle ring finger 1 (MuRF1) response to Dex. We showed that GRβ may serve as a pharmacological target for skeletal muscle growth and protection from glucocorticoid-induced catabolic signaling. Increasing GRβ levels in skeletal muscle may cause a state of glucocorticoid resistance, stabilizing muscle mass during exposure to high doses of glucocorticoids.

  5. Overexpression of Glucocorticoid Receptor β Enhances Myogenesis and Reduces Catabolic Gene Expression

    Directory of Open Access Journals (Sweden)

    Terry D. Hinds

    2016-02-01

    Full Text Available Unlike the glucocorticoid receptor α (GRα, GR β (GRβ has a truncated ligand-binding domain that prevents glucocorticoid binding, implicating GRα as the mediator of glucocorticoid-induced skeletal muscle loss. Because GRβ causes glucocorticoid resistance, targeting GRβ may be beneficial in impairing muscle loss as a result of GRα activity. The purpose of this study was to determine how the overexpression of GRβ affects myotube formation and dexamethasone (Dex responsiveness. We measured GR isoform expression in C2C12 muscle cells in response to Dex and insulin, and through four days of myotube formation. Next, lentiviral-mediated overexpression of GRβ in C2C12 was performed, and these cells were characterized for cell fusion and myotube formation, as well as sensitivity to Dex via the expression of ubiquitin ligases. GRβ overexpression increased mRNA levels of muscle regulatory factors and enhanced proliferation in myoblasts. GRβ overexpressing myotubes had an increased fusion index. Myotubes overexpressing GRβ had lower forkhead box O3 (Foxo3a mRNA levels and a blunted muscle atrophy F-box/Atrogen-1 (MAFbx and muscle ring finger 1 (MuRF1 response to Dex. We showed that GRβ may serve as a pharmacological target for skeletal muscle growth and protection from glucocorticoid-induced catabolic signaling. Increasing GRβ levels in skeletal muscle may cause a state of glucocorticoid resistance, stabilizing muscle mass during exposure to high doses of glucocorticoids.

  6. Delay Tolerance: A Therapeutic Possibility for AD/HD?

    Directory of Open Access Journals (Sweden)

    Edmund J. S. Sonuga-Barke

    2004-01-01

    on these two insights to explore the possibility that the motivational alterations underpinning delay aversion can be modified through specific training regimes in a way equivalent to that found with executive and attentional training. The requirements for such an approach are set out. Delay fading is proposed as a possible basis for reorganizing delay experience, altering the incentive value of delay (e.g., increasing tolerance for delay, thereby reducing AD/HD symptoms.

  7. ATFM airborne delays without extra fuel consumption in wind conditions

    OpenAIRE

    Delgado, L.; Prats, X.

    2012-01-01

    Air Traffic Flow Management (ATFM) regulations, such as ground holdings, are often canceled before their initially planned ending time. The ground delays impact on the cost of recovering part of the delay if the regulation is canceled, as aircraft are still at the origin airport. In previous publications, the authors have suggested a speed reduction strategy to split the assigned ATFM delay between ground delay and airborne delay. By flying at the the minimum speed that g...

  8. Performance Evaluation of Blind Tropospheric Delay correction ...

    African Journals Online (AJOL)

    lekky

    and Temperature 2 wet (GPT2w) models) for tropospheric delay correction, ... In practice, a user often employs a certain troposphere model based on the popularity ... comparisons between some of the models have been carried out in the past for .... prediction of meteorological parameter values, which are then used to ...

  9. STEMI time delays: A clinical perspective

    NARCIS (Netherlands)

    M.J. de Boer (Menko Jan); F. Zijlstra (Felix)

    2015-01-01

    textabstractSTEMI time delays have been introduced as a performance indicator or marker of quality of care. As they are only one part of a very complex medical process, one should be aware of concomitant issues that may be overlooked or even be more important with regard to clinical outcome of STEMI

  10. Third order differential equations with delay

    Directory of Open Access Journals (Sweden)

    Petr Liška

    2015-05-01

    Full Text Available In this paper, we study the oscillation and asymptotic properties of solutions of certain nonlinear third order differential equations with delay. In particular, we extend results of I. Mojsej (Nonlinear Analysis 68, 2008 and we improve conditions on the property B of N. Parhi and S. Padhi (Indian J. Pure Appl. Math., 33, 2002.

  11. Radionuclide scan findings in delayed splenic rupture

    International Nuclear Information System (INIS)

    Flickinger, F.W.; Jackson, G.L.

    1978-01-01

    An initial liver/spleen scan performed on a patient with blunt abdominal trauma was negative 3 days following the accident. A follow-up scan 7 days later showed definite evidence of splenic rupture, proved surgically. The authors conclude that, in such cases, spleen scans may be negative initially because of delayed splenic ruptures

  12. Photoemission and photoionization time delays and rates

    Science.gov (United States)

    Gallmann, L.; Jordan, I.; Wörner, H. J.; Castiglioni, L.; Hengsberger, M.; Osterwalder, J.; Arrell, C. A.; Chergui, M.; Liberatore, E.; Rothlisberger, U.; Keller, U.

    2017-01-01

    Ionization and, in particular, ionization through the interaction with light play an important role in fundamental processes in physics, chemistry, and biology. In recent years, we have seen tremendous advances in our ability to measure the dynamics of photo-induced ionization in various systems in the gas, liquid, or solid phase. In this review, we will define the parameters used for quantifying these dynamics. We give a brief overview of some of the most important ionization processes and how to resolve the associated time delays and rates. With regard to time delays, we ask the question: how long does it take to remove an electron from an atom, molecule, or solid? With regard to rates, we ask the question: how many electrons are emitted in a given unit of time? We present state-of-the-art results on ionization and photoemission time delays and rates. Our review starts with the simplest physical systems: the attosecond dynamics of single-photon and tunnel ionization of atoms in the gas phase. We then extend the discussion to molecular gases and ionization of liquid targets. Finally, we present the measurements of ionization delays in femto- and attosecond photoemission from the solid–vacuum interface. PMID:29308414

  13. Photoemission and photoionization time delays and rates

    Directory of Open Access Journals (Sweden)

    L. Gallmann

    2017-11-01

    Full Text Available Ionization and, in particular, ionization through the interaction with light play an important role in fundamental processes in physics, chemistry, and biology. In recent years, we have seen tremendous advances in our ability to measure the dynamics of photo-induced ionization in various systems in the gas, liquid, or solid phase. In this review, we will define the parameters used for quantifying these dynamics. We give a brief overview of some of the most important ionization processes and how to resolve the associated time delays and rates. With regard to time delays, we ask the question: how long does it take to remove an electron from an atom, molecule, or solid? With regard to rates, we ask the question: how many electrons are emitted in a given unit of time? We present state-of-the-art results on ionization and photoemission time delays and rates. Our review starts with the simplest physical systems: the attosecond dynamics of single-photon and tunnel ionization of atoms in the gas phase. We then extend the discussion to molecular gases and ionization of liquid targets. Finally, we present the measurements of ionization delays in femto- and attosecond photoemission from the solid–vacuum interface.

  14. Tuberculous Lymphadenitis: Skin Delayed-Type Hypersensitivity ...

    African Journals Online (AJOL)

    Tuberculous Lymphadenitis: Skin Delayed-Type Hypersensitivity Reaction and Cellular Immune Responses. ... The tuberculin skin test (TST) and peripheral blood mono-nuclear cells (PBMCs) culture were conducted using PPD. The cytokines were measured using commercial kits. Results: The mean TST was 24.6 ±8.0 ...

  15. Delay differential systems for tick population dynamics.

    Science.gov (United States)

    Fan, Guihong; Thieme, Horst R; Zhu, Huaiping

    2015-11-01

    Ticks play a critical role as vectors in the transmission and spread of Lyme disease, an emerging infectious disease which can cause severe illness in humans or animals. To understand the transmission dynamics of Lyme disease and other tick-borne diseases, it is necessary to investigate the population dynamics of ticks. Here, we formulate a system of delay differential equations which models the stage structure of the tick population. Temperature can alter the length of time delays in each developmental stage, and so the time delays can vary geographically (and seasonally which we do not consider). We define the basic reproduction number [Formula: see text] of stage structured tick populations. The tick population is uniformly persistent if [Formula: see text] and dies out if [Formula: see text]. We present sufficient conditions under which the unique positive equilibrium point is globally asymptotically stable. In general, the positive equilibrium can be unstable and the system show oscillatory behavior. These oscillations are primarily due to negative feedback within the tick system, but can be enhanced by the time delays of the different developmental stages.

  16. Moments of the Wigner delay times

    International Nuclear Information System (INIS)

    Berkolaiko, Gregory; Kuipers, Jack

    2010-01-01

    The Wigner time delay is a measure of the time spent by a particle inside the scattering region of an open system. For chaotic systems, the statistics of the individual delay times (whose average is the Wigner time delay) are thought to be well described by random matrix theory. Here we present a semiclassical derivation showing the validity of random matrix results. In order to simplify the semiclassical treatment, we express the moments of the delay times in terms of correlation functions of scattering matrices at different energies. In the semiclassical approximation, the elements of the scattering matrix are given in terms of the classical scattering trajectories, requiring one to study correlations between sets of such trajectories. We describe the structure of correlated sets of trajectories and formulate the rules for their evaluation to the leading order in inverse channel number. This allows us to derive a polynomial equation satisfied by the generating function of the moments. Along with showing the agreement of our semiclassical results with the moments predicted by random matrix theory, we infer that the scattering matrix is unitary to all orders in the semiclassical approximation.

  17. Delayed early proprioceptive information processing in schizophrenia

    DEFF Research Database (Denmark)

    Arnfred, Sidse M; Hemmingsen, RP; Parnas, Josef

    2006-01-01

    . In the patients, the early contralateral parietal activity was delayed and later central activity had increased amplitude, but gating was unaffected. The results could be understood within the "deficiency of corollary discharge" model of schizophrenia but not within the "filtering" theory. Further studies...

  18. A Delay Discounting Model of Psychotherapy Termination

    Science.gov (United States)

    Swift, Joshua K.; Callahan, Jennifer L.

    2009-01-01

    Delay discounting (DD) procedures are emerging as an important new method for psychotherapy researchers. In this paper a framework for conceptualizing existing, seemingly discrepant, research findings on termination is introduced and new directions for research are described. To illustrate the value of a DD framework, the common psychotherapy…

  19. Optimal Control for Stochastic Delay Evolution Equations

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Qingxin, E-mail: mqx@hutc.zj.cn [Huzhou University, Department of Mathematical Sciences (China); Shen, Yang, E-mail: skyshen87@gmail.com [York University, Department of Mathematics and Statistics (Canada)

    2016-08-15

    In this paper, we investigate a class of infinite-dimensional optimal control problems, where the state equation is given by a stochastic delay evolution equation with random coefficients, and the corresponding adjoint equation is given by an anticipated backward stochastic evolution equation. We first prove the continuous dependence theorems for stochastic delay evolution equations and anticipated backward stochastic evolution equations, and show the existence and uniqueness of solutions to anticipated backward stochastic evolution equations. Then we establish necessary and sufficient conditions for optimality of the control problem in the form of Pontryagin’s maximum principles. To illustrate the theoretical results, we apply stochastic maximum principles to study two examples, an infinite-dimensional linear-quadratic control problem with delay and an optimal control of a Dirichlet problem for a stochastic partial differential equation with delay. Further applications of the two examples to a Cauchy problem for a controlled linear stochastic partial differential equation and an optimal harvesting problem are also considered.

  20. Traumatic and alternating delayed intracranial hematomas

    Energy Technology Data Exchange (ETDEWEB)

    Lesoin, F.; Redford, H.; Jomin, M.; Viaud, C.; Pruvo, J.

    1984-11-01

    Repeat computed tomography has enabled us to confirm the concept of delayed hematomas. With this in mind we report two cases of alternating, post-traumatic intracranial hematomas; confirming also the role of tamponade after surgical removal of an intracranial hematoma.

  1. early versus delayed induction of labour

    African Journals Online (AJOL)

    during labour versus 18 patients (52%) in the group that was induced .... (AMG) or a delayed induction group (DIG). Sealed .... Of the 7 CSs in the DIG, 3 were for fetal heart rate .... in mind that labour was never induced later than 48 hours.

  2. Infants' Delayed Recognition Memory and Forgetting

    Science.gov (United States)

    Fagan, Joseph F., III

    1973-01-01

    Infants 21- to 25-weeks-old devoted more visual fixation to novel than familiar stimuli on immediate and delayed recognition tests. The experiments confirm the existence of long-term recognition memory for pictorial stimuli in the early months of life. (DP)

  3. Voluntary suppression of defecation delays gastric emptying

    NARCIS (Netherlands)

    Tjeerdsma, H. C.; Smout, A. J.; Akkermans, L. M.

    1993-01-01

    We wished to test the hypothesis that colonic loading with fecal material leads to delayed gastric emptying. Twelve healthy male volunteers were studied. Each of these subjects went through two randomized study periods of four days. In one of these, the subjects defecated upon urge, in the other

  4. Management of delayed nuclear power plant projects

    International Nuclear Information System (INIS)

    2005-01-01

    The IAEA assists the management of organizations responsible for Nuclear Power Plant Projects with significant delays with respect to the originally scheduled commercial operation. Several Member States have Nuclear Power Plant Projects with delays of five or more years with respect to the originally scheduled commercial operation. The degree of conformance with original construction schedules shows large variations due to several issues, including financial, economic and public opinion factors. Solving the special difficulties related with a delayed NPP project is problematic and dependent on the particular country situation. However it is not regarded as an isolated national problem but as a significant issue with a number of difficulties shared by several Member States. The IAEA collects information and supports the management of delayed NPP projects by identifying main common issues, gathering available experience and addressing specific needs. On this background the IAEA is in the position to provide unique impartial assistance based upon best international practices. This enables Member States to maintain readiness for resuming the project construction when the conditions permit and to strengthen management's abilities for the completion of the project. The IAEA's service is tailored to the needs and requirements of the requesting organization, implemented on-site by international experts and addresses areas such as project control measures, human resources, updating to technological and regulatory requirements, project data, nuclear safety review, physical protection and nuclear security and preparation to resume project construction and operation

  5. Traumatic and alternating delayed intracranial hematomas

    International Nuclear Information System (INIS)

    Lesoin, F.; Redford, H.; Jomin, M.; Viaud, C.; Pruvo, J.

    1984-01-01

    Repeat computed tomography has enabled us to confirm the concept of delayed hematomas. With this in mind we report two cases of alternating, post-traumatic intracranial hematomas; confirming also the role of tamponade after surgical removal of an intracranial hematoma. (orig.)

  6. Terrestrial Sagnac delay constraining modified gravity models

    Science.gov (United States)

    Karimov, R. Kh.; Izmailov, R. N.; Potapov, A. A.; Nandi, K. K.

    2018-04-01

    Modified gravity theories include f(R)-gravity models that are usually constrained by the cosmological evolutionary scenario. However, it has been recently shown that they can also be constrained by the signatures of accretion disk around constant Ricci curvature Kerr-f(R0) stellar sized black holes. Our aim here is to use another experimental fact, viz., the terrestrial Sagnac delay to constrain the parameters of specific f(R)-gravity prescriptions. We shall assume that a Kerr-f(R0) solution asymptotically describes Earth's weak gravity near its surface. In this spacetime, we shall study oppositely directed light beams from source/observer moving on non-geodesic and geodesic circular trajectories and calculate the time gap, when the beams re-unite. We obtain the exact time gap called Sagnac delay in both cases and expand it to show how the flat space value is corrected by the Ricci curvature, the mass and the spin of the gravitating source. Under the assumption that the magnitude of corrections are of the order of residual uncertainties in the delay measurement, we derive the allowed intervals for Ricci curvature. We conclude that the terrestrial Sagnac delay can be used to constrain the parameters of specific f(R) prescriptions. Despite using the weak field gravity near Earth's surface, it turns out that the model parameter ranges still remain the same as those obtained from the strong field accretion disk phenomenon.

  7. Maximum likelihood window for time delay estimation

    International Nuclear Information System (INIS)

    Lee, Young Sup; Yoon, Dong Jin; Kim, Chi Yup

    2004-01-01

    Time delay estimation for the detection of leak location in underground pipelines is critically important. Because the exact leak location depends upon the precision of the time delay between sensor signals due to leak noise and the speed of elastic waves, the research on the estimation of time delay has been one of the key issues in leak lovating with the time arrival difference method. In this study, an optimal Maximum Likelihood window is considered to obtain a better estimation of the time delay. This method has been proved in experiments, which can provide much clearer and more precise peaks in cross-correlation functions of leak signals. The leak location error has been less than 1 % of the distance between sensors, for example the error was not greater than 3 m for 300 m long underground pipelines. Apart from the experiment, an intensive theoretical analysis in terms of signal processing has been described. The improved leak locating with the suggested method is due to the windowing effect in frequency domain, which offers a weighting in significant frequencies.

  8. Exact, almost and delayed fault detection

    DEFF Research Database (Denmark)

    Niemann, Hans Henrik; Saberi, Ali; Stoorvogel, Anton A.

    1999-01-01

    Considers the problem of fault detection and isolation while using zero or almost zero threshold. A number of different fault detection and isolation problems using exact or almost exact disturbance decoupling are formulated. Solvability conditions are given for the formulated design problems....... The l-step delayed fault detection problem is also considered for discrete-time systems....

  9. Inhibition of androgen receptor by decoy molecules delays progression to castration-recurrent prostate cancer.

    Directory of Open Access Journals (Sweden)

    Jae-Kyung Myung

    Full Text Available Androgen receptor (AR is a member of the steroid receptor family and a therapeutic target for all stages of prostate cancer. AR is activated by ligand binding within its C-terminus ligand-binding domain (LBD. Here we show that overexpression of the AR NTD to generate decoy molecules inhibited both the growth and progression of prostate cancer in castrated hosts. Specifically, it was shown that lentivirus delivery of decoys delayed hormonal progression in castrated hosts as indicated by increased doubling time of tumor volume, prolonged time to achieve pre-castrate levels of serum prostate-specific antigen (PSA and PSA nadir. These clinical parameters are indicative of delayed hormonal progression and improved therapeutic response and prognosis. Decoys reduced the expression of androgen-regulated genes that correlated with reduced in situ interaction of the AR with androgen response elements. Decoys did not reduce levels of AR protein or prevent nuclear localization of the AR. Nor did decoys interact directly with the AR. Thus decoys did not inhibit AR transactivation by a dominant negative mechanism. This work provides evidence that the AR NTD plays an important role in the hormonal progression of prostate cancer and supports the development of AR antagonists that target the AR NTD.

  10. Restoration of Mitochondrial NAD+ Levels Delays Stem Cell Senescence and Facilitates Reprogramming of Aged Somatic Cells.

    Science.gov (United States)

    Son, Myung Jin; Kwon, Youjeong; Son, Taekwon; Cho, Yee Sook

    2016-12-01

    The fundamental tenet that aging is irreversible has been challenged by the development of reprogramming technology that can restore molecular and cellular age by reversing the progression of aging. The use of cells from aged individuals as sources for reprogramming or transplantation creates a major barrier in stem cell therapy with respect to cell quality and quantity. Here, we investigated the molecular features underlying senescence and rejuvenation during aged cell reprogramming and identified novel factors that can overcome age-associated barriers. Enzymes, such as nicotinamide nucleotide transhydrogenase (NNT) and nicotinamide mononucleotide adenylyltransferase 3 (NMNAT3), that control mitochondrial NAD + levels appear to be susceptible to aging. In aged cells, mitochondrial NAD + levels decrease, accompanied by reduced SIRT3 activity; these changes severely impede cell fate transition. However, in cells collected from aged p16 knockout mice, which exhibit delayed cellular senescence, no changes in NNT or NMNAT3 expression were found. Importantly, restoring mitochondrial NAD + levels by overexpressing NNT and NMNAT3 enhanced reprogramming efficiency of aged somatic cells and extended the lifespan of human mesenchymal stem cells by delaying replicative senescence. These results demonstrate that maintenance of mitochondrial NAD + levels is critical for reversing the mechanisms of aging and ensuring that cells collected from aged individuals are of high quality. Stem Cells 2016;34:2840-2851. © 2016 AlphaMed Press.

  11. Denials and Delays of Radioactive Material Shipments

    International Nuclear Information System (INIS)

    El-Shinawy, R.M.K.

    2011-01-01

    delays of shipments of radioactive materials forms an important issue today. Radioactive materials need to be transported using all modes of transport for use in different applications such as public health, industry, research and production of nuclear power. The transport of radioactive materials is governed by national and international regulations, which are based on the International Atomic Energy Agency (IAEA) regulations for safe transport of radioactive materials (TS-R-1). These regulations ensure high standards of safety. Recently there were increasing numbers of instances of denials and delays of shipments of radioactive materials even when complying with the regulations. The denials and delays can result in difficulties to patients and others who rely on products sterilized by radiation. Therefore there is an urgent need for a universally accepted approach to solve this problem. In response, the IAEA has formed an International Steering Committee (ISC) on denials and delays of radioactive materials. Also, it designate the National Focal Points (NFP) representative to help the ISC members and the IAEA by informing about denial operations and how they can help. The Steering Committee developed and adopted an action plan which includes the action to be taken. This plan is based on: Awareness, Training, Communication, Lobbying for marketing, Economic and Harmonization among member states. It is important to work within the mandate of the ISC and in the line of action plan on denials and delays. It identified the following network members such as: National Focal Points, Regional Coordinators, National Committee, National Representative for different modes of transport and similar bodies, Carriers, Producers and Suppliers, Different civil societies, NGO's, Ministry of transport and others.

  12. Overexpression of a novel endogenous NADH kinase in Aspergillus nidulans enhances growth

    DEFF Research Database (Denmark)

    Panagiotou, Gianni; Grotkjær, Thomas; Hofmann, Gerald

    2009-01-01

    .7.1.86) has been identified. The enzyme has a predicted molecular weight of 49 kDa. We characterised the role of this NADH kinase by genomic integration of the putative gene AN8837.2 under a strong constitutive promoter. The physiological effects of overexpressed NADH kinase in combination with different...... yield on glucose and the maximum specific growth rate increased from 0.47 g/g and 0.22 h(-1) (wild type) to 0.54 g/g and 0.26 h(-1) (NADH kinase overexpressed), respectively. The results suggest that overexpression of NADH kinase improves the growth efficiency of the cell by increasing the access...

  13. Overexpression of p53, MDM2 proteins in some atr radiation-induced skin ulcers

    International Nuclear Information System (INIS)

    Gu Qingyang; Gao Yabing; Wang Dewen; Cui Yufang; Zhao Po; Yang Zhixiang; Zhou Jie

    2000-01-01

    An animal model of radiation-induced skin ulcer was set up with 140 rats, which were locally irradiated with 35-55 Gy γ-rays. The pathological changes were observed for 1 year. Immunohistochemical studies were performed in 72 rat radiation skin ulcer specimens using anti-p53 and anti-MDM2 proteins polyclonal antibodies. The results showed that the positive rate for overexpression of p53 protein was 9.7%, and for that of MDM2 was 19.4%. The overexpression of p53 was mainly seen in the nuclei of activated squamous epithelial cells, and in fibroblasts, endotheliocytes in deeper part of the skin ulcers. The overexpression of MDM2 had the same localizations. It is suggested that the changes of p53 and MDM2, genes and proteins, may be related to the cancer transformation and poor healing of radiation-induced skin ulcers

  14. EMMPRIN overexpression in SVZ neural progenitor cells increases their migration towards ischemic cortex.

    Science.gov (United States)

    Kanemitsu, Michiko; Tsupykov, Oleg; Potter, Gaël; Boitard, Michael; Salmon, Patrick; Zgraggen, Eloisa; Gascon, Eduardo; Skibo, Galina; Dayer, Alexandre G; Kiss, Jozsef Z

    2017-11-01

    Stimulation of endogenous neurogenesis and recruitment of neural progenitors from the subventricular zone (SVZ) neurogenic site may represent a useful strategy to improve regeneration in the ischemic cortex. Here, we tested whether transgenic overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN), the regulator of matrix metalloproteinases (MMPs) expression, in endogenous neural progenitor cells (NPCs) in the subventricular zone (SVZ) could increase migration towards ischemic injury. For this purpose, we applied a lentivector-mediated gene transfer system. We found that EMMPRIN-transduced progenitors exhibited enhanced MMP-2 activity in vitro and showed improved motility in 3D collagen gel as well as in cortical slices. Using a rat model of neonatal ischemia, we showed that EMMPRIN overexpressing SVZ cells invade the injured cortical tissue more efficiently than controls. Our results suggest that EMMPRIN overexpression could be suitable approach to improve capacities of endogenous or transplanted progenitors to invade the injured cortex. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Exponential synchronization of two nonlinearly non-delayed and delayed coupled complex dynamical networks

    International Nuclear Information System (INIS)

    Zheng Song

    2012-01-01

    In this paper, the exponential synchronization between two nonlinearly coupled complex networks with non-delayed and delayed coupling is investigated with Lyapunov-Krasovskii-type functionals. Based on the stability analysis of the impulsive differential equation and the linear matrix inequality, sufficient delay-dependent conditions for exponential synchronization are derived, and a linear impulsive controller and simple updated laws are also designed. Furthermore, the coupling matrices need not be symmetric or irreducible. Numerical examples are presented to verify the effectiveness and correctness of the synchronization criteria obtained.

  16. Barley plants over-expressing the NAC transcription factor gene HvNAC005 show stunting and delay in development combined with early senescence

    DEFF Research Database (Denmark)

    Christiansen, Michael W; Matthewman, Colette; Podzimska-Sroka, Dagmara

    2016-01-01

    -expressing plants showed up-regulation of genes involved with secondary metabolism, hormone metabolism, stress, signalling, development, and transport. Up-regulation of senescence markers and hormone metabolism and signalling genes supports a role of HvNAC005 in the cross field of different hormone and signalling......The plant-specific NAC transcription factors have attracted particular attention because of their involvement in stress responses, senescence, and nutrient remobilization. The HvNAC005 gene of barley encodes a protein belonging to subgroup NAC-a6 of the NAC family. This study shows that HvNAC005...... pathways. Binding of HvNAC005 to promoter sequences of putative target genes containing the T[G/A]CGT core motif was shown by direct protein-DNA interactions of HvNAC005 with promoters for two of the up-regulated genes. In conclusion, HvNAC005 was shown to be a strong positive regulator of senescence...

  17. [Characteristic and clinical significance of DNA methyltransferase 3B overexpression in endometrial carcinoma].

    Science.gov (United States)

    Dong, Y; Zhou, M; Ba, X J; Si, J W; Li, W T; Wang, Y; Li, D; Li, T

    2016-10-18

    To determine the clinicopathological significance of the DNA methyltransferase 3B (DNMT3B) overexpression in endometrial carcinomas and to evaluate its correlation with hormone receptor status. Immunohistochemistry was performed to assess the expression of DNMT3B and hormone receptors in 104 endometrial carcinomas. DNMT3B overexpression occurred frequently in endometrioid carcinoma (EC, 54.8%) more than in nonendometrioid carcinoma (NEC, 30.0%) with statistical significance (P=0.028). Furthermore, there was a trend that EC with worse clinico-pathological variables and shorter survival had a higher DNMT3B expression, and the correlation between DNMT3B and tumor grade reached statistical significance (P=0.019).A negative correlation between DNMT3B and estrogen receptor (ER) or progesterone receptor (PR) expression was found in EC. NMT3B overexpression occurred frequently in the ER or PR negative subgroups (78.9%, 86.7%) more than in the positive subgroups (47.7%, 47.8%) with statistical significance (P=0.016, P=0.006). In addition, the DNMT3B overexpression increased in tumors with both ER and PR negative expression (92.9%, P=0.002). However, no such correlation was found in NEC (P>0.05). Sequence analyses demonstrated multiple ER and PR binding sites in the promoter regions of DNMT3B gene. This study showed that the expression of DNMT3B in EC and NEC was different. DNMT3B overexpression in EC was associated with the worse clinicopathological variables and might have predictive value. The methylation status of EC and NEC maybe different. In addition, in EC, DNMT3B overexpression negatively correlated with ER or PR expression. In NEC, the correlation between DNMT3B and ER or PR status was not present.

  18. Cyclin-dependent kinase inhibitor 3 is overexpressed in hepatocellular carcinoma and promotes tumor cell proliferation

    International Nuclear Information System (INIS)

    Xing, Chunyang; Xie, Haiyang; Zhou, Lin; Zhou, Wuhua; Zhang, Wu; Ding, Songming; Wei, Bajin; Yu, Xiaobo; Su, Rong; Zheng, Shusen

    2012-01-01

    Highlights: ► CDKN3 is commonly overexpressed in HCC and is associated with poor clinical outcome. ► Overexpression of CDKN3 could stimulate the proliferation of HCC cells by promoting G1/S transition. ► CDKN3 could inhibit the expression of p21 in HCC cells. ► Overexpression of CDKN3 has no effect on apoptosis and invasion of HCC cells. ► We identified 61 genes co-expressed with CDKN3, and BIRC5 was located at the center of the co-expression network. -- Abstract: Cyclin-dependent kinase inhibitor 3 (CDKN3) belongs to the protein phosphatases family and has a dual function in cell cycling. The function of this gene has been studied in several kinds of cancers, but its role in human hepatocellular carcinoma (HCC) remains to be elucidated. In this study, we found that CDKN3 was frequently overexpressed in both HCC cell lines and clinical samples, and this overexpression was correlated with poor tumor differentiation and advanced tumor stage. Functional studies showed that overexpression of CDKN3 could promote cell proliferation by stimulating G1-S transition but has no impact on cell apoptosis and invasion. Microarray-based co-expression analysis identified a total of 61 genes co-expressed with CDKN3, with most of them involved in cell proliferation, and BIRC5 was located at the center of CDKN3 co-expression network. These results suggest that CDKN3 acts as an oncogene in human hepatocellular carcinoma and antagonism of CDKN3 may be of interest for the treatment of HCC.

  19. Aurora-A overexpression and aneuploidy predict poor outcome in serous ovarian carcinoma.

    Science.gov (United States)

    Lassus, Heini; Staff, Synnöve; Leminen, Arto; Isola, Jorma; Butzow, Ralf

    2011-01-01

    Aurora-A is a potential oncogene and therapeutic target in ovarian carcinoma. It is involved in mitotic events and overexpression leads to centrosome amplification and chromosomal instability. The objective of this study was to evaluate the clinical significance of Aurora-A and DNA ploidy in serous ovarian carcinoma. Serous ovarian carcinomas were analysed for Aurora-A protein by immunohistochemistry (n=592), Aurora-A copy number by CISH (n=169), Aurora-A mRNA by real-time PCR (n=158) and DNA ploidy by flowcytometry (n=440). Overexpression of Aurora-A was found in 27% of the tumors, cytoplasmic overexpression in 11% and nuclear in 17%. The cytoplasmic and nuclear overexpression were nearly mutually exclusive. Both cytoplasmic and nuclear overexpression were associated with shorter survival, high grade, high proliferation index and aberrant p53. Interestingly, only cytoplasmic expression was associated with aneuploidy and expression of phosphorylated Aurora-A. DNA ploidy was associated with poor patient outcome as well as aggressive clinicopathological parameters. In multivariate analysis, Aurora-A overexpression appeared as an independent prognostic factor for disease-free survival, together with grade, stage and ploidy. Aurora-A protein expression is strongly linked with poor patient outcome and aggressive disease characteristics, which makes Aurora-A a promising biomarker and a potential therapeutic target in ovarian carcinoma. Cytoplasmic and nuclear Aurora-A protein may have different functions. DNA aneuploidy is a strong predictor of poor prognosis in serous ovarian carcinoma. Copyright © 2010 Elsevier Inc. All rights reserved.

  20. Striatal dopamine transmission is subtly modified in human A53Tα-synuclein overexpressing mice.

    Directory of Open Access Journals (Sweden)

    Nicola J Platt

    Full Text Available Mutations in, or elevated dosage of, SNCA, the gene for α-synuclein (α-syn, cause familial Parkinson's disease (PD. Mouse lines overexpressing the mutant human A53Tα-syn may represent a model of early PD. They display progressive motor deficits, abnormal cellular accumulation of α-syn, and deficits in dopamine-dependent corticostriatal plasticity, which, in the absence of overt nigrostriatal degeneration, suggest there are age-related deficits in striatal dopamine (DA signalling. In addition A53Tα-syn overexpression in cultured rodent neurons has been reported to inhibit transmitter release. Therefore here we have characterized for the first time DA release in the striatum of mice overexpressing human A53Tα-syn, and explored whether A53Tα-syn overexpression causes deficits in the release of DA. We used fast-scan cyclic voltammetry to detect DA release at carbon-fibre microelectrodes in acute striatal slices from two different lines of A53Tα-syn-overexpressing mice, at up to 24 months. In A53Tα-syn overexpressors, mean DA release evoked by a single stimulus pulse was not different from wild-types, in either dorsal striatum or nucleus accumbens. However the frequency responsiveness of DA release was slightly modified in A53Tα-syn overexpressors, and in particular showed slight deficiency when the confounding effects of striatal ACh acting at presynaptic nicotinic receptors (nAChRs were antagonized. The re-release of DA was unmodified after single-pulse stimuli, but after prolonged stimulation trains, A53Tα-syn overexpressors showed enhanced recovery of DA release at old age, in keeping with elevated striatal DA content. In summary, A53Tα-syn overexpression in mice causes subtle changes in the regulation of DA release in the striatum. While modest, these modifications may indicate or contribute to striatal dysfunction.

  1. c-MET Overexpression in Colorectal Cancer: A Poor Prognostic Factor for Survival.

    Science.gov (United States)

    Lee, Su Jin; Lee, Jeeyun; Park, Se Hoon; Park, Joon Oh; Lim, Ho Yeong; Kang, Won Ki; Park, Young Suk; Kim, Seung Tae

    2018-03-02

    Increased mesenchymal-epithelial transition factor gene (c-MET) expression in several human malignancies is related to increased tumor progression and is a new potential drug target for several types of cancers. In the present study, we investigated the incidence of c-MET overexpression and its prognostic significance in patients with colorectal cancer (CRC). We retrospectively reviewed the data from 255 stage IV CRC patients who had results from a c-MET immunohistochemical test at Samsung Medical Center. We explored the relationships between c-MET overexpression and clinicopathological features and survival. Primary tumor sites were 67 right-sided colon, 98 left-sided colon, and 90 rectum. Forty-two patients (16.7%) had poorly differentiated or mucinous carcinoma. Among the 255 patients, 39 (15.3%) exhibited c-MET overexpression. There was no significant difference in the prevalence of c-MET overexpression according to primary site, histologic differentiation, molecular markers, or metastatic sites. In a comparison of the tumor response to first-line chemotherapy according to the level of c-MET expression, we found no significant difference in either partial response or disease control rate. In the survival analysis, patients with c-MET overexpression had significantly shorter overall survival (39 vs. 27 months; P = .018) and progression-free survival (PFS) during bevacizumab treatment (10 vs. 7 months; P = .024). c-MET overexpression, which was detected in 39 CRC patients (15.3%) irrespective of primary sites or molecular markers, indicated a poor survival prognosis and predicted shorter PFS during bevacizumab treatment in patients with CRC. Further studies are warranted to elucidate the value of c-MET-targeted therapy in CRC patients. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  2. BDNF Overexpression Exhibited Bilateral Effect on Neural Behavior in SCT Mice Associated with AKT Signal Pathway.

    Science.gov (United States)

    Chen, Mei-Rong; Dai, Ping; Wang, Shu-Fen; Song, Shu-Hua; Wang, Hang-Ping; Zhao, Ya; Wang, Ting-Hua; Liu, Jia

    2016-10-01

    Spinal cord injury (SCI), a severe health problem in worldwide, was commonly associated with functional disability and reduced quality of life. As the expression of brain-derived neurotrophic factor (BDNF) was substantial event in injured spinal cord, we hypothesized whether BDNF-overexpression could be in favor of the recovery of both sensory function and hindlimb function after SCI. By using BDNF-overexpression transgene mice [CMV-BDNF 26 (CB26) mice] we assessed the role of BDNF on the recovery of neurological behavior in spinal cord transection (SCT) model. BMS score and tail-flick test was performed to evaluate locomotor function and sensory function, respectively. Immunohistochemistry was employed to detect the location and the expression of BDNF, NeuN, 5-HT, GAP-43, GFAP as well as CGRP, and the level of p-AKT and AKT were examined through western blot analysis. BDNF overexpressing resulted in significant locomotor functional recovery from 21 to 28 days after SCT, compared with wild type (WT)+SCT group. Meanwhile, the NeuN, 5-HT and GAP-43 positive cells were markedly increased in ventral horn in BDNF overexpression animals, compared with WT mice with SCT. Moreover, the crucial molecular signal, p-AKT/AKT has been largely up-regulated, which is consistent with the improvement of locomotor function. However, in this study, thermal hyperpathia encountered in sham (CB26) group and WT+SCT mice and further aggravated in CB26 mice after SCT. Also, following SCT, the significant augment of positive-GFAP astrocytes and CGRP fibers were found in WT+SCT mice, and further increase was seen in BDNF over-expression transgene mice. BDNF-overexpression may not only facilitate the recovery of locomotor function via AKT pathway, but also contributed simultaneously to thermal hyperalgesia after SCT.

  3. Enhanced production of GDP-L-fucose by overexpression of NADPH regenerator in recombinant Escherichia coli.

    Science.gov (United States)

    Lee, Won-Heong; Chin, Young-Wook; Han, Nam Soo; Kim, Myoung-Dong; Seo, Jin-Ho

    2011-08-01

    Biosynthesis of guanosine 5'-diphosphate-L-fucose (GDP-L-fucose) requires NADPH as a reducing cofactor. In this study, endogenous NADPH regenerating enzymes such as glucose-6-phosphate dehydrogenase (G6PDH), isocitrate dehydrogenase (Icd), and NADP(+)-dependent malate dehydrogenase (MaeB) were overexpressed to increase GDP-L-fucose production in recombinant Escherichia coli. The effects of overexpression of each NADPH regenerating enzyme on GDP-L-fucose production were investigated in a series of batch and fed-batch fermentations. Batch fermentations showed that overexpression of G6PDH was the most effective for GDP-L-fucose production. However, GDP-L-fucose production was not enhanced by overexpression of G6PDH in the glucose-limited fed-batch fermentation. Hence, a glucose feeding strategy was optimized to enhance GDP-L-fucose production. Fed-batch fermentation with a pH-stat feeding mode for sufficient supply of glucose significantly enhanced GDP-L-fucose production compared with glucose-limited fed-batch fermentation. A maximum GDP-L-fucose concentration of 235.2 ± 3.3 mg l(-1), corresponding to a 21% enhancement in the GDP-L-fucose production compared with the control strain overexpressing GDP-L-fucose biosynthetic enzymes only, was achieved in the pH-stat fed-batch fermentation of the recombinant E. coli overexpressing G6PDH. It was concluded that sufficient glucose supply and efficient NADPH regeneration are crucial for NADPH-dependent GDP-L-fucose production in recombinant E. coli.

  4. Overexpression of Hypoxia-Inducible Factor-1α Exacerbates Endothelial Barrier Dysfunction Induced by Hypoxia

    Directory of Open Access Journals (Sweden)

    Pei Wang

    2013-09-01

    Full Text Available Background/Aims: The mechanisms involved in endothelial barrier dysfunction induced by hypoxia are incompletely understood. There is debate about the role of hypoxia-inducible factor-1α (HIF-1α in endothelial barrier disruption. The aim of this study was to investigate the effect of genetic overexpression of HIF-1α on barrier function and the underlying mechanisms in hypoxic endothelial cells. Methods: The plasmid pcDNA3.1/V5-His-HIF-1α was stably transfected into human endothelial cells. The cells were exposed to normoxia or hypoxia. The mRNA and protein expressions of HIF-1α were detected by RT-PCR and Western blot respectively. The barrier function was assessed by measuring the transendothelial electrical resistance (TER. The Western blot analysis was used to determine the protein expression of glucose transporter-1 (GLUT-1, zonular occludens-1 (ZO-1, occludin, and myosin light chain kinase (MLCK in endothelial cells. The mRNA expression of proinflammatory cytokines was detected by qRT-PCR. Results: Genetic overexpression of HIF-1α significantly increased the mRNA and protein expression of HIF-1α in endothelial cells. The overexpression of HIF-1α enhanced the hypoxia-induced increase of HIF-1α and GLUT-1 protein expression. HIF-1α overexpression not only exacerbated hypoxia-induced endothelial barrier dysfunction but also augmented hypoxia-induced up-regulation of MLCK protein expression. HIF-1α overexpression also enhanced IL-1β, IL-6 and TNF-α mRNA expression. Conclusion: We provide evidence that genetic overexpression of HIF-1α aggravates the hypoxia-induced endothelial barrier dysfunction via enhancing the up-regulation of MLCK protein expression caused by hypoxia, suggesting a potential role for HIF-1α in the pathogenesis of endothelial barrier dysfunction in hypoxia.

  5. Overexpression of cellular glutathione peroxidase rescues homocyst(e)ine-induced endothelial dysfunction

    Science.gov (United States)

    Weiss, Norbert; Zhang, Ying-Yi; Heydrick, Stanley; Bierl, Charlene; Loscalzo, Joseph

    2001-01-01

    Homocyst(e)ine (Hcy) inhibits the expression of the antioxidant enzyme cellular glutathione peroxidase (GPx-1) in vitro and in vivo, which can lead to an increase in reactive oxygen species that inactivate NO and promote endothelial dysfunction. In this study, we tested the hypothesis that overexpression of GPx-1 can restore the normal endothelial phenotype in hyperhomocyst(e)inemic states. Heterozygous cystathionine β-synthase-deficient (CBS(−/+)) mice and their wild-type littermates (CBS(+/+)) were crossbred with mice that overexpress GPx-1 [GPx-1(tg+) mice]. GPx-1 activity was 28% lower in CBS(−/+)/GPx-1(tg−) compared with CBS(+/+)/GPx-1(tg−) mice (P < 0.05), and CBS(−/+) and CBS(+/+) mice overexpressing GPx-1 had 1.5-fold higher GPx-1 activity compared with GPx-1 nontransgenic mice (P < 0.05). Mesenteric arterioles of CBS(−/+)/GPx-1(tg−) mice showed vasoconstriction to superfusion with β-methacholine and bradykinin (P < 0.001 vs. all other groups), whereas nonhyperhomocyst(e)inemic mice [CBS(+/+)/GPx-1(tg−) and CBS(+/+)/GPx-1(tg+) mice] demonstrated dose-dependent vasodilation in response to both agonists. Overexpression of GPx-1 in hyperhomocyst(e)inemic mice restored the normal endothelium-dependent vasodilator response. Bovine aortic endothelial cells (BAEC) were transiently transfected with GPx-1 and incubated with dl-homocysteine (HcyH) or l-cysteine. HcyH incubation decreased GPx-1 activity in sham-transfected BAEC (P < 0.005) but not in GPx-1-transfected cells. Nitric oxide release from BAEC was significantly decreased by HcyH but not cysteine, and GPx-1 overexpression attenuated this decrease. These findings demonstrate that overexpression of GPx-1 can compensate for the adverse effects of Hcy on endothelial function and suggest that the adverse vascular effects of Hcy are at least partly mediated by oxidative inactivation of NO. PMID:11606774

  6. Overexpression of BAX INHIBITOR-1 Links Plasma Membrane Microdomain Proteins to Stress.

    Science.gov (United States)

    Ishikawa, Toshiki; Aki, Toshihiko; Yanagisawa, Shuichi; Uchimiya, Hirofumi; Kawai-Yamada, Maki

    2015-10-01

    BAX INHIBITOR-1 (BI-1) is a cell death suppressor widely conserved in plants and animals. Overexpression of BI-1 enhances tolerance to stress-induced cell death in plant cells, although the molecular mechanism behind this enhancement is unclear. We recently found that Arabidopsis (Arabidopsis thaliana) BI-1 is involved in the metabolism of sphingolipids, such as the synthesis of 2-hydroxy fatty acids, suggesting the involvement of sphingolipids in the cell death regulatory mechanism downstream of BI-1. Here, we show that BI-1 affects cell death-associated components localized in sphingolipid-enriched microdomains of the plasma membrane in rice (Oryza sativa) cells. The amount of 2-hydroxy fatty acid-containing glucosylceramide increased in the detergent-resistant membrane (DRM; a biochemical counterpart of plasma membrane microdomains) fraction obtained from BI-1-overexpressing rice cells. Comparative proteomics analysis showed quantitative changes of DRM proteins in BI-1-overexpressing cells. In particular, the protein abundance of FLOTILLIN HOMOLOG (FLOT) and HYPERSENSITIVE-INDUCED REACTION PROTEIN3 (HIR3) markedly decreased in DRM of BI-1-overexpressing cells. Loss-of-function analysis demonstrated that FLOT and HIR3 are required for cell death by oxidative stress and salicylic acid, suggesting that the decreased levels of these proteins directly contribute to the stress-tolerant phenotypes in BI-1-overexpressing rice cells. These findings provide a novel biological implication of plant membrane microdomains in stress-induced cell death, which is negatively modulated by BI-1 overexpression via decreasing the abundance of a set of key proteins involved in cell death. © 2015 American Society of Plant Biologists. All Rights Reserved.

  7. Amplification and overexpression of aurora kinase A (AURKA) in immortalized human ovarian epithelial (HOSE) cells.

    Science.gov (United States)

    Chung, C M; Man, C; Jin, Y; Jin, C; Guan, X Y; Wang, Q; Wan, T S K; Cheung, A L M; Tsao, S W

    2005-07-01

    Immortalization is an early and essential step of human carcinogenesis. Amplification of chromosome 20q has been shown to be a common event in immortalized cells and cancers. We have previously reported that gain and amplification of chromosome 20q is a non-random and common event in immortalized human ovarian surface epithelial (HOSE) cells. The chromosome 20q harbors genes including TGIF2 (20q11.2-q12), AIB1 (20q12), PTPN1 (20q13.1), ZNF217 (20q13.2), and AURKA (20q13.2-q13.3), which were previously reported to be amplified and overexpressed in ovarian cancers. Some of these genes may be involved in immortalization of HOSE cells and represent crucial premalignant changes in ovarian surface epithelium. Investigation of the involvement of these genes was examined in four pairs of pre-crisis (preimmortalized) and post-crisis (immortalized) HOSE cells. Overexpression of AURKA (Aurora kinase A), also known as BTAK and STK15, by both real time-quantitative polymerase chain reaction (RT-QPCR) and Western blotting was detected in all the four immortalized HOSE cells examined while overexpression of AIB1 and ZNF217 was observed in two of four immortalized HOSE cells examined. Overexpression of TGIF2 and PTPN1 was not significant in our immortalized HOSE cell systems. The degree of overexpression of AURKA was shown to be closely associated with the amplification of chromosome 20q in immortalized HOSE cells. Fluorescence in situ hybridization (FISH) with labeled P1 artificial clone (PAC) confirmed the amplification of the chromosomal region (20q13.2-13.3) where AURKA resides. DNA amplification of AURKA was also confirmed using semi-quantitative PCR. Our study showed that amplification and overexpression of AURKA is a common and significant event during immortalization of HOSE cells and may represent an important premalignant change in ovarian carcinogenesis. Copyright (c) 2005 Wiley-Liss, Inc.

  8. [Effect of luxS overexpression on biofilm formation by Streptococcus mutans].

    Science.gov (United States)

    He, Zhiyan; Wang, Yuxia; Huang, Zhengwei

    2015-09-01

    To evaluate the effect of quorum sensing luxS gene on biofilm formation through construction of a luxS overexpression strain by Streptococcus mutans (Sm). In order to construct pIB-luxS plasmid, the luxS gene fragment amplified by PCR was inserted into the shuttle plasmid pIB169 by corresponding double digests. The pIB-luxS plasmid was linearized electro-transformed into Sm cell and the overexpression strain was selected on chloramphenicol plate and testified by electrophoresis and western blot. The growth rate of both Sm wild type strain and its luxS overexpression strain were observed. Methyl thiazolyl tetrazolium (MTT) assay method was used to compare the biofilm formation quantification by both strains at different time points and containing different sucrose. The structures of the biofilms were observed by using confocal laser scanning microscopy, and biofilm-related gene expressions were investigated by real-time PCR. All experiments were performed in triplicate. The luxS overexpression strain was successfully constructed and confirmed by electrophoresis and Western blotting. The planktonic growth mode of the wild-type and luxS overexpression strain showed no difference, but biofilm formed by Sm overexpression strain was 0.400 ± 0.009 and 0.609 ± 0.041 at 14 and 24 h, higher than the wild type strain biofilm at the same time point (0.352 ± 0.028 and 0.533 ± 0.014, respectively, P overexpression strain raised to 1.041 ± 0.038, higher than that by the wild type strain (0.831 ± 0.020, P overexpression strain aggregated into distinct clusters on structure, genes expression including gtfB, ftf, gbpB, relA, brpA, smu630, comDE, vicR were increased (6.10 ± 0.12, 3.34 ± 0.07, 8.75 ± 0.13, 2.96 ± 0.04, 5.20 ± 0.19, 2.20 ± 0.06, 2.32 ± 0.07 and 10.67 ± 0.57 fold) compared to the wild-type strain (P < 0.05). Quorum sensing luxS gene can promote the biofilm formation of Sm.

  9. Overexpression and surface localization of the Chlamydia trachomatis major outer membrane protein in Escherichia coli

    DEFF Research Database (Denmark)

    Koehler, JF; Birkelund, Svend; Stephens, RS

    1992-01-01

    The Chlamydia trachomatis major outer membrane protein (MOMP) is the quantitatively predominant surface protein which has important functional, structural and antigenic properties. We have cloned and overexpressed the MOMP in Escherichia coli. The MOMP is surface exposed in C. trachomatis....... The induction of MOMP expression had a rapidly lethal effect on the L2rMOMP E. coli clone. Although no genetic system exists for Chlamydia, development of a stable, inducible E. coli clone which overexpresses the chlamydial MOMP permits a study of the biological properties of the MOMP, including...

  10. Overexpression of isocitrate lyase-glyoxylate bypass influence on metabolism in Aspergillus niger

    DEFF Research Database (Denmark)

    Meijer, Susan Lisette; Otero, José Manuel; Olivares Hernandez, Roberto

    2009-01-01

    of the cells was investigated. Inhibition of SDH was expected to lead to succinate production, but this was not observed. There was an increase in citrate and oxalate production in the wild-type strain. Furthermore, in the strain with over-expression of icl the organic acid production shifted from fumarate...... towards malate production when malonate was added to the cultivation medium. Overall, the icl over-expression and malonate addition had a significant impact on metabolism and on organic acid production profiles. Although the expected succinate and malate formation was not observed, a distinct...

  11. Overexpression of thrombospondin-1 reduces growth and vascular index but not perfusion in glioblastoma

    DEFF Research Database (Denmark)

    Kragh, Michael; Quistorff, Bjørn; Tenan, Mirna

    2002-01-01

    Little is known about the effects of antiangiogenic therapy on perfusion of human tumors and the mechanisms by which tumors can adapt to these treatments and recur. Here, we examined the effects of serial passaging of LN-229 human glioma xenografts overexpressing thrombospondin (TSP)-1 on tumor...... vascularity was estimated by noninvasive near infrared spectroscopy measuring blood volume at 800 +/- 10 nm and by histological vessel scores in CD31-immunostained cryosections. The tumor perfusion was assessed by noninvasive laser Doppler flowmetry. Overexpression of TSP-1 significantly inhibited tumor....... Elucidation of the mechanisms that allow this to happen has important consequences for the understanding of tumor recurrence after antiangiogenic therapy....

  12. Delay, doubt, and decision: how delaying a choice reduces the appeal of (descriptively) normative options.

    Science.gov (United States)

    van de Ven, Niels; Gilovich, Thomas; Zeelenberg, Marcel

    2010-04-01

    To help explain a regularity in democratic elections, we examined whether choosing to delay making a choice between a focal option and an alternative tends to make people subsequently less likely to choose what they would otherwise have chosen. The results of two experiments demonstrated that participants who were induced to delay making a decision were indeed less likely to choose the descriptively normative option. An additional experiment that primed a sense of doubt in participants provided support for a self-perception account of this result. Electing to delay making a choice is interpreted as an indication of doubt--doubt that tends to be attributed to the most prominent option. Delay-induced doubt about the normative option makes it less likely to be selected.

  13. Delay-range-dependent exponential H∞ synchronization of a class of delayed neural networks

    International Nuclear Information System (INIS)

    Karimi, Hamid Reza; Maass, Peter

    2009-01-01

    This article aims to present a multiple delayed state-feedback control design for exponential H ∞ synchronization problem of a class of delayed neural networks with multiple time-varying discrete delays. On the basis of the drive-response concept and by introducing a descriptor technique and using Lyapunov-Krasovskii functional, new delay-range-dependent sufficient conditions for exponential H ∞ synchronization of the drive-response structure of neural networks are driven in terms of linear matrix inequalities (LMIs). The explicit expression of the controller gain matrices are parameterized based on the solvability conditions such that the drive system and the response system can be exponentially synchronized. A numerical example is included to illustrate the applicability of the proposed design method.

  14. Synchronization of nonidentical chaotic neural networks with leakage delay and mixed time-varying delays

    Directory of Open Access Journals (Sweden)

    Cao Jinde

    2011-01-01

    Full Text Available Abstract In this paper, an integral sliding mode control approach is presented to investigate synchronization of nonidentical chaotic neural networks with discrete and distributed time-varying delays as well as leakage delay. By considering a proper sliding surface and constructing Lyapunov-Krasovskii functional, as well as employing a combination of the free-weighting matrix method, Newton-Leibniz formulation and inequality technique, a sliding mode controller is designed to achieve the asymptotical synchronization of the addressed nonidentical neural networks. Moreover, a sliding mode control law is also synthesized to guarantee the reachability of the specified sliding surface. The provided conditions are expressed in terms of linear matrix inequalities, and are dependent on the discrete and distributed time delays as well as leakage delay. A simulation example is given to verify the theoretical results.

  15. Adaptive modification of the delayed feedback control algorithm with a continuously varying time delay

    International Nuclear Information System (INIS)

    Pyragas, V.; Pyragas, K.

    2011-01-01

    We propose a simple adaptive delayed feedback control algorithm for stabilization of unstable periodic orbits with unknown periods. The state dependent time delay is varied continuously towards the period of controlled orbit according to a gradient-descent method realized through three simple ordinary differential equations. We demonstrate the efficiency of the algorithm with the Roessler and Mackey-Glass chaotic systems. The stability of the controlled orbits is proven by computation of the Lyapunov exponents of linearized equations. -- Highlights: → A simple adaptive modification of the delayed feedback control algorithm is proposed. → It enables the control of unstable periodic orbits with unknown periods. → The delay time is varied continuously according to a gradient descend method. → The algorithm is embodied by three simple ordinary differential equations. → The validity of the algorithm is proven by computation of the Lyapunov exponents.

  16. A distributed delay approach for modeling delayed outcomes in pharmacokinetics and pharmacodynamics studies.

    Science.gov (United States)

    Hu, Shuhua; Dunlavey, Michael; Guzy, Serge; Teuscher, Nathan

    2018-04-01

    A distributed delay approach was proposed in this paper to model delayed outcomes in pharmacokinetics and pharmacodynamics studies. This approach was shown to be general enough to incorporate a wide array of pharmacokinetic and pharmacodynamic models as special cases including transit compartment models, effect compartment models, typical absorption models (either zero-order or first-order absorption), and a number of atypical (or irregular) absorption models (e.g., parallel first-order, mixed first-order and zero-order, inverse Gaussian, and Weibull absorption models). Real-life examples were given to demonstrate how to implement distributed delays in Phoenix ® NLME™ 8.0, and to numerically show the advantages of the distributed delay approach over the traditional methods.

  17. Stochastic two-delay differential model of delayed visual feedback effects on postural dynamics.

    Science.gov (United States)

    Boulet, Jason; Balasubramaniam, Ramesh; Daffertshofer, Andreas; Longtin, André

    2010-01-28

    We report on experiments and modelling involving the 'visuo-postural control loop' in the upright stance. We experimentally manipulated an artificial delay to the visual feedback during standing, presented at delays ranging from 0 to 1 s in increments of 250 ms. Using stochastic delay differential equations, we explicitly modelled the centre-of-pressure (COP) and centre-of-mass (COM) dynamics with two independent delay terms for vision and proprioception. A novel 'drifting fixed point' hypothesis was used to describe the fluctuations of the COM with the COP being modelled as a faster, corrective process of the COM. The model was in good agreement with the data in terms of probability density functions, power spectral densities, short- and long-term correlations (Hurst exponents) as well the critical time between the two ranges. This journal is © 2010 The Royal Society

  18. Overexpression of the protein phosphatase 2A regulatory subunit a gene ZmPP2AA1 improves low phosphate tolerance by remodeling the root system architecture of maize.

    Directory of Open Access Journals (Sweden)

    Jiemin Wang

    Full Text Available Phosphate (Pi limitation is a constraint for plant growth and development in many natural and agricultural ecosystems. In this study, a gene encoding Zea mays L. protein phosphatase 2A regulatory subunit A, designated ZmPP2AA1, was induced in roots by low Pi availability. The function of the ZmPP2AA1 gene in maize was analyzed using overexpression and RNA interference. ZmPP2AA1 modulated root gravitropism, negatively regulated primary root (PR growth, and stimulated the development of lateral roots (LRs. A detailed characterization of the root system architecture (RSA in response to different Pi concentrations with or without indole-3-acetic acid and 1-N-naphthylphthalamic acid revealed that auxin was involved in the RSA response to low Pi availability. Overexpression of ZmPP2AA1 enhanced tolerance to Pi starvation in transgenic maize in hydroponic and soil pot experiments. An increased dry weight (DW, root-to-shoot ratio, and total P content and concentration, along with a delayed and reduced accumulation of anthocyanin in overexpressing transgenic maize plants coincided with their highly branched root system and increased Pi uptake capability under low Pi conditions. Inflorescence development of the ZmPP2AA1 overexpressing line was less affected by low Pi stress, resulting in higher grain yield per plant under Pi deprivation. These data reveal the biological function of ZmPP2AA1, provide insights into a linkage between auxin and low Pi responses, and drive new strategies for the efficient utilization of Pi by maize.

  19. Overexpression of eIF-5A2 in mice causes accelerated organismal aging by increasing chromosome instability

    Directory of Open Access Journals (Sweden)

    Chen Leilei

    2011-05-01

    Full Text Available Abstract Background Amplification of 3q26 is one of the most frequent genetic alterations in many human malignancies. Recently, we isolated a novel oncogene eIF-5A2 within the 3q26 region. Functional study has demonstrated the oncogenic role of eIF-5A2 in the initiation and progression of human cancers. In the present study, we aim to investigate the physiological and pathological effect of eIF-5A2 in an eIF-5A2 transgenic mouse model. Methods An eIF-5A2 transgenic mouse model was generated using human eIF-5A2 cDNA. The eIF-5A2 transgenic mice were characterized by histological and immunohistochemistry analyses. The aging phenotypes were further characterized by wound healing, bone X-ray imaging and calcification analysis. Mouse embryo fibroblasts (MEF were isolated to further investigate molecular mechanism of eIF-5A2 in aging. Results Instead of resulting in spontaneous tumor formation, overexpression of eIF-5A2 accelerated the aging process in adult transgenic mice. This included decreased growth rate and body weight, shortened life span, kyphosis, osteoporosis, delay of wound healing and ossification. Investigation of the correlation between cellular senescence and aging showed that cellular senescence is not required for the aging phenotypes in eIF-5A2 mice. Interestingly, we found that activation of eIF-5A2 repressed p19 level and therefore destabilized p53 in transgenic mouse embryo fibroblast (MEF cells. This subsequently allowed for the accumulation of chromosomal instability, such as errors in cell dividing during metaphase and anaphase. Additionally, a significantly increase in number of aneuploidy cells (p Conclusion These observations suggest that eIF-5A2 mouse models could accelerate organismal aging by increasing chromosome instability.

  20. Topology identification of the complex networks with non-delayed and delayed coupling

    International Nuclear Information System (INIS)

    Guo Wanli; Chen Shihua; Sun Wen

    2009-01-01

    In practical situation, there exists many uncertain information in complex networks, such as the topological structures. So the topology identification is an important issue in the research of the complex networks. Based on LaSalle's invariance principle, in this Letter, an adaptive controlling method is proposed to identify the topology of a weighted general complex network model with non-delayed and delayed coupling. Finally, simulation results show that the method is effective.

  1. Chaos control in delayed chaotic systems via sliding mode based delayed feedback

    Energy Technology Data Exchange (ETDEWEB)

    Vasegh, Nastaran [Faculty of Electrical Engineering, K.N. Toosi University of Technology, Seyed Khandan Bridge, Shariati St. 16314, P.O. Box 16315-1355, Tehran (Iran, Islamic Republic of)], E-mail: vasegh@eetd.kntu.ac.ir; Sedigh, Ali Khaki [Faculty of Electrical Engineering, K.N. Toosi University of Technology, Seyed Khandan Bridge, Shariati St. 16314, P.O. Box 16315-1355, Tehran (Iran, Islamic Republic of)

    2009-04-15

    This paper investigates chaos control for scalar delayed chaotic systems using sliding mode control strategy. Sliding surface design is based on delayed feedback controller. It is shown that the proposed controller can achieve stability for an arbitrary unstable fixed point (UPF) or unstable periodic orbit (UPO) with arbitrary period. The chaotic system used in this study to illustrate the theoretical concepts is the well known Mackey-Glass model. Simulation results show the effectiveness of the designed nonlinear sliding mode controller.

  2. Chaos control in delayed chaotic systems via sliding mode based delayed feedback

    International Nuclear Information System (INIS)

    Vasegh, Nastaran; Sedigh, Ali Khaki

    2009-01-01

    This paper investigates chaos control for scalar delayed chaotic systems using sliding mode control strategy. Sliding surface design is based on delayed feedback controller. It is shown that the proposed controller can achieve stability for an arbitrary unstable fixed point (UPF) or unstable periodic orbit (UPO) with arbitrary period. The chaotic system used in this study to illustrate the theoretical concepts is the well known Mackey-Glass model. Simulation results show the effectiveness of the designed nonlinear sliding mode controller.

  3. Pinning synchronization of the complex networks with non-delayed and delayed coupling

    International Nuclear Information System (INIS)

    Guo Wanli; Austin, Francis; Chen Shihua; Sun Wen

    2009-01-01

    In this Letter, without assuming the symmetry of the coupling matrix, we investigate the global synchronization of the complex networks with non-delayed and delayed coupling based on the pinning controllers. Some sufficient conditions for the global synchronization by adding linear and adaptive feedback controllers to a part of nodes are obtained. Numerical examples are also provided to demonstrate the effectiveness of the theory.

  4. Delay-Dependent Asymptotic Stability of Cohen-Grossberg Models with Multiple Time-Varying Delays

    Directory of Open Access Journals (Sweden)

    Xiaofeng Liao

    2007-01-01

    Full Text Available Dynamical behavior of a class of Cohen-Grossberg models with multiple time-varying delays is studied in detail. Sufficient delay-dependent criteria to ensure local and global asymptotic stabilities of the equilibrium of this network are derived by constructing suitable Lyapunov functionals. The obtained conditions are shown to be less conservative and restrictive than those reported in the known literature. Some numerical examples are included to demonstrate our results.

  5. A novel delay-dependent criterion for delayed neural networks of neutral type

    International Nuclear Information System (INIS)

    Lee, S.M.; Kwon, O.M.; Park, Ju H.

    2010-01-01

    This Letter considers a robust stability analysis method for delayed neural networks of neutral type. By constructing a new Lyapunov functional, a novel delay-dependent criterion for the stability is derived in terms of LMIs (linear matrix inequalities). A less conservative stability criterion is derived by using nonlinear properties of the activation function of the neural networks. Two numerical examples are illustrated to show the effectiveness of the proposed method.

  6. Maternal Obesity: Risks for Developmental Delays in Early Childhood.

    Science.gov (United States)

    Duffany, Kathleen O'Connor; McVeigh, Katharine H; Kershaw, Trace S; Lipkind, Heather S; Ickovics, Jeannette R

    2016-02-01

    To assess the risk for neurodevelopmental delays for children of mothers who were obese (≥200 pounds) prior to pregnancy, and to characterize delays associated with maternal obesity among children referred to and found eligible to receive Early Intervention Program services. We conducted a retrospective cohort study (N = 541,816) using a population-based New York City data warehouse with linked birth and Early Intervention data. Risks for children suspected of a delay and 'significantly delayed', with two moderate or one severe delay, were calculated. Among the group of children eligible by delay for Early Intervention, analyses assessed risk for being identified with a moderate-to-severe delay across each of five functional domains as well as risks for multiple delays. Children of mothers who were obese were more likely to be suspected of a delay (adjusted RR 1.19 [CI 1.15-1.22]) and borderline association for 'significantly delayed' (adjusted RR 1.01 [CI 1.00-1.02). Among children eligible by delay, children of mothers who were obese evidenced an increased risk for moderate-to-severe cognitive (adjusted RR 1.04 [CI 1.02-1.07]) and physical (adjusted RR 1.04 [CI 1.01-1.08]) delays and for global developmental delay (adjusted RR 1.05 [CI 1.01-1.08]). Maternal obesity is associated with increased risk of developmental delay in offspring. Among children with moderate or severe delays, maternal obesity is associated with increased risk of cognitive and physical delays as well as with increased risk for global developmental delay. While causation remains uncertain, this adds to the growing body of research reporting an association between maternal obesity and neurodevelopmental delays in offspring.

  7. Delay-Dependent Guaranteed Cost Control of an Interval System with Interval Time-Varying Delay

    Directory of Open Access Journals (Sweden)

    Xiao Min

    2009-01-01

    Full Text Available This paper concerns the problem of the delay-dependent robust stability and guaranteed cost control for an interval system with time-varying delay. The interval system with matrix factorization is provided and leads to less conservative conclusions than solving a square root. The time-varying delay is assumed to belong to an interval and the derivative of the interval time-varying delay is not a restriction, which allows a fast time-varying delay; also its applicability is broad. Based on the Lyapunov-Ktasovskii approach, a delay-dependent criterion for the existence of a state feedback controller, which guarantees the closed-loop system stability, the upper bound of cost function, and disturbance attenuation lever for all admissible uncertainties as well as out perturbation, is proposed in terms of linear matrix inequalities (LMIs. The criterion is derived by free weighting matrices that can reduce the conservatism. The effectiveness has been verified in a number example and the compute results are presented to validate the proposed design method.

  8. REASONS FOR PATIENT DELAYS & HEALTH SYSTEM DELAYS FOR TUBERCULOSIS IN SOUTH INDIA

    Directory of Open Access Journals (Sweden)

    Kapil Goel

    2011-12-01

    Full Text Available Background: Globally, the burden of Tuberculosis is escalating. Early diagnosis and prompt initiation of tuberculosis treatment is essential for an effective tuberculosis control programme. Objectives: To study the self reported reasons for patient and health system (diagnosis & treatment delays in Tuberculosis patients. Methods: A community based cross sectional study was conducted among 98 new sputum positive TB cases aged > 15 years registered under RNTCP from Oct 2006 to June 2007 & receiving treatment under DOTS in Udupi taluk by interviewing them. Results: Total 98 patients were recruited and 68% were males. Out of 17 patients with patient delays, 82% felt that their symptoms were not severe, 71% felt that patient delay was due to lack of awareness and 71% did not take it seriously. Out of 86 patients with health system delays, 82.6% of patients mentioned that doctor has not advised for sputum examination, 76.7% of patients told that they first consulted a private doctor, 21% of them mentioned that doctor was unaware to diagnose TB. Conclusion: Symptoms not severe is the main reason for the patient delay and doctor didn’t advise for sputum examination is the main reason for health system delays.

  9. Lxr-driven enterocyte lipid droplet formation delays transport of ingested lipids.

    Science.gov (United States)

    Cruz-Garcia, Lourdes; Schlegel, Amnon

    2014-09-01

    Liver X receptors (Lxrs) are master regulators of cholesterol catabolism, driving the elimination of cholesterol from the periphery to the lumen of the intestine. Development of pharmacological agents to activate Lxrs has been hindered by synthetic Lxr agonists' induction of hepatic lipogenesis and hypertriglyceridemia. Elucidating the function of Lxrs in regulating enterocyte lipid handling might identify novel aspects of lipid metabolism that are pharmacologically amenable. We took a genetic approach centered on the single Lxr gene nr1h3 in zebrafish to study the role of Lxr in enterocyte lipid metabolism. Loss of nr1h3 function causes anticipated gene regulatory changes and cholesterol intolerance, collectively reflecting high evolutionary conservation of zebrafish Lxra function. Intestinal nr1h3 activation delays transport of absorbed neutral lipids, with accumulation of neutral lipids in enterocyte cytoplasmic droplets. This delay in transport of ingested neutral lipids protects animals from hypercholesterolemia and hepatic steatosis induced by a high-fat diet. On a gene regulatory level, Lxra induces expression of acsl3a, which encodes acyl-CoA synthetase long-chain family member 3a, a lipid droplet-anchored protein that directs fatty acyl chains into lipids. Forced overexpression of acls3a in enterocytes delays, in part, the appearance of neutral lipids in the vasculature of zebrafish larvae. Activation of Lxr in the intestine cell-autonomously regulates the rate of delivery of absorbed lipids by inducting a temporary lipid intestinal droplet storage depot. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

  10. Time-delayed feedback control of diffusion in random walkers

    Science.gov (United States)

    Ando, Hiroyasu; Takehara, Kohta; Kobayashi, Miki U.

    2017-07-01

    Time delay in general leads to instability in some systems, while specific feedback with delay can control fluctuated motion in nonlinear deterministic systems to a stable state. In this paper, we consider a stochastic process, i.e., a random walk, and observe its diffusion phenomenon with time-delayed feedback. As a result, the diffusion coefficient decreases with increasing delay time. We analytically illustrate this suppression of diffusion by using stochastic delay differential equations and justify the feasibility of this suppression by applying time-delayed feedback to a molecular dynamics model.

  11. Fundamentals of Delayed Coking Joint Industry Project

    Energy Technology Data Exchange (ETDEWEB)

    Michael Volk; Keith Wisecarver

    2003-09-26

    Delayed coking evolved steadily over the early to mid 1900s to enable refiners to convert high boiling, residual petroleum fractions to light products such as gasoline. Pound for pound, coking is the most energy intensive of any operation in a modern refinery. Large amounts of energy are required to heat the thick, poor-quality petroleum residuum to the 900 to 950 degrees F required to crack the heavy hydrocarbon molecules into lighter, more valuable products. One common misconception of delayed coking is that the product coke is a disadvantage. Although coke is a low valued (near zero economic value) byproduct, compared to transportation fuels, there is a significant worldwide trade and demand for coke as it is an economical fuel. Coke production has increased steadily over the last ten years, with further increases forecast for the foreseeable future. Current domestic production is near 111,000 tons per day. A major driving force behind this increase is the steady decline in crude quality available to refiners. Crude slates are expected to grow heavier with higher sulfur contents while environmental restrictions are expected to significantly reduce the demand for high-sulfur residual fuel oil. Light sweet crudes will continue to be available and in even greater demand than they are today. Refiners will be faced with the choice of purchasing light sweet crudes at a premium price, or adding bottom of the barrel upgrading capability, through additional new investments, to reduce the production of high-sulfur residual fuel oil and increase the production of low-sulfur distillate fuels. A second disadvantage is that liquid products from cokers frequently are unstable, i.e., they rapidly form gum and sediments. Because of intermediate investment and operating costs, delayed coking has increased in popularity among refiners worldwide. Based on the 2000 Worldwide Refining Survey published in the Oil and Gas, the delayed coking capacity for 101 refineries around the world

  12. Delayed Luminescence and Biophotons from Biological Materials

    Science.gov (United States)

    Knoesel, Ernst; Hann, Patrick; Garzon, Maria; Pfeiffer, Erik; Lofland, Samuel

    2008-03-01

    There has recently been increased interest in the field of biophotonics, since it is a non-invasive technique. Many biological systems, such as yeast, bacteria, leaves, seeds, and algae display the unusual phenomenon of a weak, delayed luminescence on the timescale of seconds to minutes after transient illumination. It is also observed that the time decay of the biophotonic emission is not exponential, even after the delay, and that there can be oscillations in intensity with time, which depend on the duration of the illumination. Results from two types of yeast, i.e. bread yeast, and saccharomyces, as well as those from several types of algae are presented. Possible mechanisms for the source of the ultraweak photon emission are discussed.

  13. Convergent dynamics for multistable delayed neural networks

    International Nuclear Information System (INIS)

    Shih, Chih-Wen; Tseng, Jui-Pin

    2008-01-01

    This investigation aims at developing a methodology to establish convergence of dynamics for delayed neural network systems with multiple stable equilibria. The present approach is general and can be applied to several network models. We take the Hopfield-type neural networks with both instantaneous and delayed feedbacks to illustrate the idea. We shall construct the complete dynamical scenario which comprises exactly 2 n stable equilibria and exactly (3 n − 2 n ) unstable equilibria for the n-neuron network. In addition, it is shown that every solution of the system converges to one of the equilibria as time tends to infinity. The approach is based on employing the geometrical structure of the network system. Positively invariant sets and componentwise dynamical properties are derived under the geometrical configuration. An iteration scheme is subsequently designed to confirm the convergence of dynamics for the system. Two examples with numerical simulations are arranged to illustrate the present theory

  14. Estimation of network path segment delays

    Science.gov (United States)

    Nichols, Kathleen Marie

    2018-05-01

    A method for estimation of a network path segment delay includes determining a scaled time stamp for each packet of a plurality of packets by scaling a time stamp for each respective packet to minimize a difference of at least one of a frequency and a frequency drift between a transport protocol clock of a host and a monitoring point. The time stamp for each packet is provided by the transport protocol clock of the host. A corrected time stamp for each packet is determined by removing from the scaled time stamp for each respective packet, a temporal offset between the transport protocol clock and the monitoring clock by minimizing a temporal delay variation of the plurality of packets traversing a segment between the host and the monitoring point.

  15. Approximating chaotic saddles for delay differential equations.

    Science.gov (United States)

    Taylor, S Richard; Campbell, Sue Ann

    2007-04-01

    Chaotic saddles are unstable invariant sets in the phase space of dynamical systems that exhibit transient chaos. They play a key role in mediating transport processes involving scattering and chaotic transients. Here we present evidence (long chaotic transients and fractal basins of attraction) of transient chaos in a "logistic" delay differential equation. We adapt an existing method (stagger-and-step) to numerically construct the chaotic saddle for this system. This is the first such analysis of transient chaos in an infinite-dimensional dynamical system, and in delay differential equations in particular. Using Poincaré section techniques we illustrate approaches to visualizing the saddle set, and confirm that the saddle has the Cantor-like fractal structure consistent with a chaotic saddle generated by horseshoe-type dynamics.

  16. Differential games in economic systems with delays

    Science.gov (United States)

    Kim, A. V.; Kormyshev, V. M.; Novikov, M. Yu.; Nikonov, M. A.

    2017-11-01

    In the paper, we consider application of i-smooth analysis (A.V. Kim, 2015) to differential games with delays in economics (Dockner E.J., et all, 2000; R. Isaacs, 1999). The approach is developed in the framework of the theory of positional differential games (N.N. Krasovskii, A.I. Subbotin, 1988; A.V. Kryazhimskii, Yu.S. Osipov, 1973; Yu.S. Osipov, J. Appl. Math. Mech. Vol. 35, № 1, № 6, 1971) and is based on application of the extremal shift strategy. We consider basic notions and constructions of the approach-evasion problem for linear systems with delays. The necessary and sufficient conditions of solvability the approach-evasion problem in terms of special u-stable sets are presented in another paper.

  17. Delayed reactions to reusable protective gloves.

    Science.gov (United States)

    Pontén, Ann; Dubnika, Inese

    2009-04-01

    The materials in plastic protective gloves are thought to cause less contact allergy than rubber gloves. Our aim was to estimate the frequency of delayed reactions to different types of reusable protective gloves among dermatitis patients. 2 x 2 cm pieces of polyvinyl chloride (PVC) gloves, nitrile gloves, and natural rubber latex (NRL) gloves were tested as is in consecutive dermatitis patients tested with the baseline series. Among 658 patients, 6 patients reacted to PVC gloves and 6 patients to the NRL gloves. None reacted to both these types of gloves. Five of six patients with reactions to rubber gloves reacted to thiuram mix in the baseline series. Delayed reactions to reusable PVC gloves may be as common as to reusable NRL gloves. In contrast to most reactions to the NRL glove, the reactions to the PVC glove had no obvious association with reactions to any allergen(s) in the baseline series.

  18. Approximating chaotic saddles for delay differential equations

    Science.gov (United States)

    Taylor, S. Richard; Campbell, Sue Ann

    2007-04-01

    Chaotic saddles are unstable invariant sets in the phase space of dynamical systems that exhibit transient chaos. They play a key role in mediating transport processes involving scattering and chaotic transients. Here we present evidence (long chaotic transients and fractal basins of attraction) of transient chaos in a “logistic” delay differential equation. We adapt an existing method (stagger-and-step) to numerically construct the chaotic saddle for this system. This is the first such analysis of transient chaos in an infinite-dimensional dynamical system, and in delay differential equations in particular. Using Poincaré section techniques we illustrate approaches to visualizing the saddle set, and confirm that the saddle has the Cantor-like fractal structure consistent with a chaotic saddle generated by horseshoe-type dynamics.

  19. Delayed chromosomal instability induced by DNA damage

    International Nuclear Information System (INIS)

    Morgan, W.F.; Marder, B.A.; Day, J.P.

    1994-01-01

    Cellular exposure to DNA damaging agents rapidly results in a dose dependent increase in chromosomal breakage and gross structural chromosomal rearrangements. Over recent years, evidence has been accumulating indicating genomic instability can manifest multiple generations after cellular exposure to physical and chemical DNA damaging agents. Genomic instability manifests in the progeny of surviving cells, and has been implicated in mutation, gene application, cellular transformation, and cell killing. To investigate chromosome instability following DNA damage, we have used fluorescence in situ hybridization to detect chromosomal rearrangements in a human/hamster somatic hybrid cell line following exposure to ionizing radiation. Delayed chromosomal instability was detected when multiple populations of uniquely arranged metaphases were observed in clonal isolates raised from single cells surviving X-irradiation many generations after exposure. At higher radiation doses, chromosomal instability was observed in a relatively high frequency of surviving clones and, in general, those clones showed delayed chromosome instability also showed reduced survival as measured by colony forming ability

  20. Energy management - The delayed flap approach

    Science.gov (United States)

    Bull, J. S.

    1976-01-01

    Flight test evaluation of a Delayed Flap approach procedure intended to provide reductions in noise and fuel consumption is underway using the NASA CV-990 test aircraft. Approach is initiated at a high airspeed (240 kt) and in a drag configuration that allows for low thrust. The aircraft is flown along the conventional ILS glide slope. A Fast/Slow message display signals the pilot when to extend approach flaps, landing gear, and land flaps. Implementation of the procedure in commercial service may require the addition of a DME navigation aid co-located with the ILS glide slope transmitter. The Delayed Flap approach saves 250 lb of fuel over the Reduced Flap approach, with a 95 EPNdB noise contour only 43% as large.

  1. Tropospheric Delay from VLBI and GNSS Measurements

    Science.gov (United States)

    Gubanov, V. S.

    2018-02-01

    Using an updated version of the QUASAR software package developed at the Institute of Applied Astronomy of the Russian Academy of Sciences, we have processed the VLBI observations within the international CONT14 program (May 6-20, 2014), in which a global network of 17 stations was involved (a total of 250 000 observations). The package update concerned the optimization of data structure and the refinement of stochastic models for the random variations in wet tropospheric delay and atomic clock difference. The main goal of this paper is to compare the VLBI determinations of the tropospheric delay with its independent determinations using global navigation satellite systems (GNSS). We show that both these determinations agree well between themselves only in the case of a global analysis of the VLBI observations, where the VLBI station coordinates are also refined, along with the tropospheric delay and the clock synchronization and Earth orientation parameters. If, alternatively, the station coordinates are insufficiently accurate and are not refined from VLBI observations, then it is appropriate not to determine the tropospheric delay from these observations, but to take it from the publicly accessible independent GNSS data. However, this requires that the VLBI and GNSS techniques operate simultaneously at a common observing site. We have established the shortcomings of the universally accepted method of stabilizing the global solution associated with the absence of a criterion for choosing reference stations and radio sources. Two ways of their elimination are proposed: (i) introducing a coordinated list of weight factors for the errors in the coordinates of such stations and sources into the stabilization algorithm and (ii) adopting a coordinated list of stations and sources the refinement of whose coordinates is not required at all for a certain time.

  2. Climate models with delay differential equations

    Science.gov (United States)

    Keane, Andrew; Krauskopf, Bernd; Postlethwaite, Claire M.

    2017-11-01

    A fundamental challenge in mathematical modelling is to find a model that embodies the essential underlying physics of a system, while at the same time being simple enough to allow for mathematical analysis. Delay differential equations (DDEs) can often assist in this goal because, in some cases, only the delayed effects of complex processes need to be described and not the processes themselves. This is true for some climate systems, whose dynamics are driven in part by delayed feedback loops associated with transport times of mass or energy from one location of the globe to another. The infinite-dimensional nature of DDEs allows them to be sufficiently complex to reproduce realistic dynamics accurately with a small number of variables and parameters. In this paper, we review how DDEs have been used to model climate systems at a conceptual level. Most studies of DDE climate models have focused on gaining insights into either the global energy balance or the fundamental workings of the El Niño Southern Oscillation (ENSO) system. For example, studies of DDEs have led to proposed mechanisms for the interannual oscillations in sea-surface temperature that is characteristic of ENSO, the irregular behaviour that makes ENSO difficult to forecast and the tendency of El Niño events to occur near Christmas. We also discuss the tools used to analyse such DDE models. In particular, the recent development of continuation software for DDEs makes it possible to explore large regions of parameter space in an efficient manner in order to provide a "global picture" of the possible dynamics. We also point out some directions for future research, including the incorporation of non-constant delays, which we believe could improve the descriptive power of DDE climate models.

  3. Superconducting delay lines and chirp filters

    International Nuclear Information System (INIS)

    Hoefer, G.J.; Kratz, H.A.

    1993-01-01

    High temperature superconductor (HTSC) thin films are now good enough to realize certain devices, particularly passive analog broadband devices requiring only a single layer of high quality material. This is especially true for long delay lines and related structures, e. g. chirp filters, where low loss and dispersion result in large usable bandwidths. The availability of these devices may hasten the commercialization of the high temperature superconductors, because they take full advantage of their unique properties. (orig.)

  4. Climate models with delay differential equations.

    Science.gov (United States)

    Keane, Andrew; Krauskopf, Bernd; Postlethwaite, Claire M

    2017-11-01

    A fundamental challenge in mathematical modelling is to find a model that embodies the essential underlying physics of a system, while at the same time being simple enough to allow for mathematical analysis. Delay differential equations (DDEs) can often assist in this goal because, in some cases, only the delayed effects of complex processes need to be described and not the processes themselves. This is true for some climate systems, whose dynamics are driven in part by delayed feedback loops associated with transport times of mass or energy from one location of the globe to another. The infinite-dimensional nature of DDEs allows them to be sufficiently complex to reproduce realistic dynamics accurately with a small number of variables and parameters. In this paper, we review how DDEs have been used to model climate systems at a conceptual level. Most studies of DDE climate models have focused on gaining insights into either the global energy balance or the fundamental workings of the El Niño Southern Oscillation (ENSO) system. For example, studies of DDEs have led to proposed mechanisms for the interannual oscillations in sea-surface temperature that is characteristic of ENSO, the irregular behaviour that makes ENSO difficult to forecast and the tendency of El Niño events to occur near Christmas. We also discuss the tools used to analyse such DDE models. In particular, the recent development of continuation software for DDEs makes it possible to explore large regions of parameter space in an efficient manner in order to provide a "global picture" of the possible dynamics. We also point out some directions for future research, including the incorporation of non-constant delays, which we believe could improve the descriptive power of DDE climate models.

  5. Dynamics in a delayed-neural network

    International Nuclear Information System (INIS)

    Yuan Yuan

    2007-01-01

    In this paper, we consider a neural network of four identical neurons with time-delayed connections. Some parameter regions are given for global, local stability and synchronization using the theory of functional differential equations. The root distributions in the corresponding characteristic transcendental equation are analyzed, Pitchfork bifurcation, Hopf and equivariant Hopf bifurcations are investigated by revealing the center manifolds and normal forms. Numerical simulations are shown the agreements with the theoretical results

  6. Direct 'delay' reductions of the Toda equation

    International Nuclear Information System (INIS)

    Joshi, Nalini

    2009-01-01

    A new direct method of obtaining reductions of the Toda equation is described. We find a canonical and complete class of all possible reductions under certain assumptions. The resulting equations are ordinary differential-difference equations, sometimes referred to as delay-differential equations. The representative equation of this class is hypothesized to be a new version of one of the classical Painleve equations. The Lax pair associated with this equation is obtained, also by reduction. (fast track communication)

  7. CERN boss quashes LHC delay rumours

    CERN Multimedia

    2007-01-01

    "Robert Aymar, the director general of CERN, has dispelled rumours that a series of buckled electrical connectors at the Large Hadron Collider will delay the accelerator's official start-up date of May 2008. Writing in this week's CERN Bulletin, Aymar says that the problem concerns only a small percentage of the connectors and that it is "business as usual" for bringing the new accelerator online." (1,5 page)

  8. Bilingualism delays clinical manifestation of Alzheimer's disease

    OpenAIRE

    Woumans, Evy; Santens, Patrick; Sieben, Anne; Versijpt, Jan; Stevens, Michaël; Duyck, Wouter

    2015-01-01

    The current study investigated the effects of bilingualism on the clinical manifestation of Alzheimer's disease (AD) in a European sample of patients. We assessed all incoming AD patients in two university hospitals within a specified timeframe. Sixty-nine monolinguals and 65 bilinguals diagnosed with probable AD were compared for time of clinical AD manifestation and diagnosis. The influence of other potentially interacting variables was also examined. Results indicated a significant delay f...

  9. Accelerating Smaller Cutbacks to Delay Larger Ones?

    DEFF Research Database (Denmark)

    Tepe, Markus; Vanhuysse, Pieter

    2012-01-01

    . Investigating both medium and large cutbacks in ageing welfare states, we test whether, in addition to conventional demographic and economic variables, political-institutional variables capturing partisanship (political ideology), electioneering (political cycle), and institutional constraints (political...... effects of unemployment and population aging: these socio-demographic variables tend to delay large-size cutbacks, but to accelerate medium-size cutbacks in pension generosity, possibly because they function as alarm bell signals urging policymakers to take still feasible incremental action through...

  10. Delayed Antiwindup Control Using a Decoupling Structure

    Directory of Open Access Journals (Sweden)

    Huawei Zhu

    2013-01-01

    Full Text Available This paper investigates the antiwindup (AW control problem for plants with input saturation. The AW compensator is not activated as soon as input saturation occurs as usual. A delayed decoupling structure is first proposed. Then, appropriate linear matrix inequalities (LMIs are developed to determine a plant-order AW compensator. Effectiveness of the presented AW technique is illustrated by a fighter aircraft model.

  11. Torness delay is storing up trouble

    International Nuclear Information System (INIS)

    Cavenagh, Andrew.

    1994-01-01

    A recent decision by the Scottish Office to delay planning permission for the construction of a 50 million dry store for spent nuclear fuel at Torness Power Station is proving frustrating and inexplicable to many in the nuclear industry. The possible reasons for this apparent about face in government policy on spent fuel management are debated and the economic ramifications of the decision for British Nuclear Fuels Limited (BNFL), if the store were to go ahead, are outlined. (UK)

  12. Earth system commitments due to delayed mitigation

    International Nuclear Information System (INIS)

    Pfister, Patrik L; Stocker, Thomas F

    2016-01-01

    As long as global CO 2 emissions continue to increase annually, long-term committed Earth system changes grow much faster than current observations. A novel metric linking this future growth to policy decisions today is the mitigation delay sensitivity (MDS), but MDS estimates for Earth system variables other than peak temperature (ΔT max ) are missing. Using an Earth System Model of Intermediate Complexity, we show that the current emission increase rate causes a ΔT max increase roughly 3–7.5 times as fast as observed warming, and a millenial steric sea level rise (SSLR) 7–25 times as fast as observed SSLR, depending on the achievable rate of emission reductions after the peak of emissions. These ranges are only slightly affected by the uncertainty range in equilibrium climate sensitivity, which is included in the above values. The extent of ocean acidification at the end of the century is also strongly dependent on the starting time and rate of emission reductions. The preservable surface ocean area with sufficient aragonite supersaturation for coral reef growth is diminished globally at an MDS of roughly 25%–80% per decade. A near-complete loss of this area becomes unavoidable if mitigation is delayed for a few years to decades. Also with respect to aragonite, 12%–18% of the Southern Ocean surface become undersaturated per decade, if emission reductions are delayed beyond 2015–2040. We conclude that the consequences of delaying global emission reductions are much better captured if the MDS of relevant Earth system variables is communicated in addition to current trends and total projected future changes. (letter)

  13. Delayed somatic effects following extended radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Slanina, J

    1977-10-27

    A group of 135 patients was investigated, who suffered from Hodgkin's disease with long-term remission following radiotherapy. By restricting the investigations to the patient group with long-term remission and correlative examinations, differentiation was made between exclusive or principal delayed radiation effects and delayed effects due to other factors. The study reports the most significant results obtained in the fields of catamnesis, laboratory diagnostics, hematology, pulmology, cardiology, thyroid function tests, neurology, andrology and dermatology. Due to the numerous detectable delayed effects the group of patients with long-term remission receives a special status. Although those effects are in no proportion to the deletary risks of an untreated Hodgkin's disease and though they are consequently tolerable in the present state of the therapeutic development, they must initiate the completion of the therapeutic concept including performance of radiotherapy and aftercare, because only then the risk for the patient provoked by these effects, which ranges beyond the malignity of this disease can be reduced or prevented.

  14. PROMPT Ia SUPERNOVAE ARE SIGNIFICANTLY DELAYED

    International Nuclear Information System (INIS)

    Raskin, Cody; Scannapieco, Evan; Rhoads, James; Della Valle, Massimo

    2009-01-01

    The time delay between the formation of a population of stars and the onset of type Ia supernovae (SNe Ia) sets important limits on the masses and nature of SN Ia progenitors. Here, we use a new observational technique to measure this time delay by comparing the spatial distributions of SNe Ia to their local environments. Previous work attempted such analyses encompassing the entire host of each SN Ia, yielding inconclusive results. Our approach confines the analysis only to the relevant portions of the hosts, allowing us to show that even so-called prompt SNe Ia that trace star formation on cosmic timescales exhibit a significant delay time of 200-500 million years. This implies that either the majority of Ia companion stars have main-sequence masses less than 3 M sun , or that most SNe Ia arise from double white dwarf binaries. Our results are also consistent with a SNe Ia rate that traces the white dwarf formation rate, scaled by a fixed efficiency factor.

  15. Best matching Barenblatt profiles are delayed

    International Nuclear Information System (INIS)

    Dolbeault, Jean; Toscani, Giuseppe

    2015-01-01

    The growth of the second moments of the solutions of fast diffusion equations is asymptotically governed by the behavior of self-similar solutions. However, at next order, there is a correction term which amounts to a delay depending on the nonlinearity and on a distance of the initial data to the set of self-similar Barenblatt solutions. This distance can be measured in terms of a relative entropy to the best matching Barenblatt profile. This best matching Barenblatt function determines a scale. In new variables based on this scale, which are given by a self-similar change of variables if and only if the initial datum is one of the Barenblatt profiles, the typical scale is monotone and has a limit. Coming back to original variables, the best matching Barenblatt profile is delayed compared to the self-similar solution with same initial second moment as the initial datum. Such a delay is a new phenomenon, which has to be taken into account for instance when fitting experimental data. (paper)

  16. Atrial fibrillation and delayed gastric emptying.

    Directory of Open Access Journals (Sweden)

    Isadora C Botwinick

    Full Text Available BACKGROUND: Atrial fibrillation and delayed gastric emptying (DGE are common after pancreaticoduodenectomy. Our aim was to investigate a potential relationship between atrial fibrillation and DGE, which we defined as failure to tolerate a regular diet by the 7(th postoperative day. METHODS: We performed a retrospective chart review of 249 patients who underwent pancreaticoduodenectomy at our institution between 2000 and 2009. Data was analyzed with Fisher exact test for categorical variables and Mann-Whitney U or unpaired T-test for continuous variables. RESULTS: Approximately 5% of the 249 patients included in the analysis experienced at least one episode of postoperative atrial fibrillation. Median age of patients with atrial fibrillation was 74 years, compared with 66 years in patients without atrial fibrillation (p = 0.0005. Patients with atrial fibrillation were more likely to have a history of atrial fibrillation (p = 0.03. 92% of the patients with atrial fibrillation suffered from DGE, compared to 46% of patients without atrial fibrillation (p = 0.0007. This association held true when controlling for age. CONCLUSION: Patients with postoperative atrial fibrillation are more likely to experience delayed gastric emptying. Interventions to manage delayed gastric function might be prudent in patients at high risk for postoperative atrial fibrillation.

  17. Delayed shear enhancement in mesoscale atmospheric dispersion

    Energy Technology Data Exchange (ETDEWEB)

    Moran, M.D. [Atmospheric Environment Service, Ontario (Canada); Pielke, R.A. [Colorado State Univ., Fort Collins, CO (United States)

    1994-12-31

    Mesoscale atmospheric dispersion (MAD) is more complicated than smaller-scale dispersion because the mean wind field can no longer be considered steady or horizontally homogeneous over mesoscale time and space scales. Wind shear also plays a much more important role on the mesoscale: horizontal dispersion can be enhanced and often dominated by vertical wind shear on these scales through the interaction of horizontal differential advection and vertical mixing. Just over 30 years ago, Pasquill suggested that this interaction need not be simultaneous and that the combination of differential horizontal advection with delayed or subsequent vertical mixing could maintain effective horizontal diffusion in spite of temporal or spatial reductions in boundary-layer turbulence intensity. This two-step mechanism has not received much attention since then, but a recent analysis of observations from and numerical simulations of two mesoscale tracer experiments suggests that delayed shear enhancement can play an important role in MAD. This paper presents an overview of this analysis, with particular emphasis on the influence of resolvable vertical shear on MAD in these two case studies and the contributions made by delayed shear enhancement.

  18. Development of delayed radiation necrosis. Case report

    Energy Technology Data Exchange (ETDEWEB)

    Ohara, ShigFeki; Takagi, Terumasa [Meitetsu Hospital, Nagoya (Japan); Shibata, Taichiro; Nagai, Hajime

    1983-04-01

    The authors discussed the developing process of delayed radiation necrosis of the brain from the case of a 42-year-old female who developed intracranial hypertension and left hemiparesis 5 and a half years after radiotherapy for pituitary adenoma. The initial sign of radiation necrosis was from a CT scan taken 3 and a half years after radiotherapy showing an irregular low density lesion in the right temporal lobe. CT scan 2 years later demonstrated displacement of the midline structures to the left and a larger low density lesion with partially high density in the right MCA territory that was enhanced with intravenous contrast medium. Recovery after a right temporal lobectomy and administration of steroid hormone were uneventful. Eight months later there were no signs of raised intracranial pressure nor of neurological deficits. Tissues obtained from the right temporal lobe at lobectomy revealed the characteristic changes of delayed radiation necrosis; a mixture of fresh, recent, and old vascular lesions in the same specimen. From these findings, it was speculated that delayed radiation necrosis might initially occur within several years after radiotherapy and might gradually take a progressive and extended course, even in cases whose clinical symptoms develop much later.

  19. Oncolytic adenovirus targeting cyclin E overexpression repressed tumor growth in syngeneic immunocompetent mice

    International Nuclear Information System (INIS)

    Cheng, Pei-Hsin; Rao, Xiao-Mei; Wechman, Stephen L.; Li, Xiao-Feng; McMasters, Kelly M.; Zhou, Heshan Sam

    2015-01-01

    Clinical trials have indicated that preclinical results obtained with human tumor xenografts in mouse models may overstate the potential of adenovirus (Ad)-mediated oncolytic therapies. We have previously demonstrated that the replication of human Ads depends on cyclin E dysregulation or overexpression in cancer cells. ED-1 cell derived from mouse lung adenocarcinomas triggered by transgenic overexpression of human cyclin E may be applied to investigate the antitumor efficacy of oncolytic Ads. Ad-cycE was used to target cyclin E overexpression in ED-1 cells and repress tumor growth in a syngeneic mouse model for investigation of oncolytic virotherapies. Murine ED-1 cells were permissive for human Ad replication and Ad-cycE repressed ED-1 tumor growth in immunocompetent FVB mice. ED-1 cells destroyed by oncolytic Ads in tumors were encircled in capsule-like structures, while cells outside the capsules were not infected and survived the treatment. Ad-cycE can target cyclin E overexpression in cancer cells and repress tumor growth in syngeneic mouse models. The capsule structures formed after Ad intratumoral injection may prevent viral particles from spreading to the entire tumor. The online version of this article (doi:10.1186/s12885-015-1731-x) contains supplementary material, which is available to authorized users

  20. Overexpression of cypin alters dendrite morphology, single neuron activity, and network properties via distinct mechanisms

    Science.gov (United States)

    Rodríguez, Ana R.; O'Neill, Kate M.; Swiatkowski, Przemyslaw; Patel, Mihir V.; Firestein, Bonnie L.

    2018-02-01

    Objective. This study investigates the effect that overexpression of cytosolic PSD-95 interactor (cypin), a regulator of synaptic PSD-95 protein localization and a core regulator of dendrite branching, exerts on the electrical activity of rat hippocampal neurons and networks. Approach. We cultured rat hippocampal neurons and used lipid-mediated transfection and lentiviral gene transfer to achieve high levels of cypin or cypin mutant (cypinΔPDZ PSD-95 non-binding) expression cellularly and network-wide, respectively. Main results. Our analysis revealed that although overexpression of cypin and cypinΔPDZ increase dendrite numbers and decrease spine density, cypin and cypinΔPDZ distinctly regulate neuronal activity. At the single cell level, cypin promotes decreases in bursting activity while cypinΔPDZ reduces sEPSC frequency and further decreases bursting compared to cypin. At the network level, by using the Fano factor as a measure of spike count variability, cypin overexpression results in an increase in variability of spike count, and this effect is abolished when cypin cannot bind PSD-95. This variability is also dependent on baseline activity levels and on mean spike rate over time. Finally, our spike sorting data show that overexpression of cypin results in a more complex distribution of spike waveforms and that binding to PSD-95 is essential for this complexity. Significance. Our data suggest that dendrite morphology does not play a major role in cypin action on electrical activity.