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Sample records for huntingtin levels modulate

  1. Full-length huntingtin levels modulate body weight by influencing insulin-like growth factor 1 expression

    DEFF Research Database (Denmark)

    Pouladi, Mahmoud A; Xie, Yuanyun; Skotte, Niels Henning

    2010-01-01

    of the IGF-1 pathway in mediating the effect of htt on body weight. IGF-1 expression was examined in transgenic mouse lines expressing different levels of FL wild-type (WT) htt (YAC18 mice), FL mutant htt (YAC128 and BACHD mice) and truncated mutant htt (shortstop mice). We demonstrate that htt influences...... body weight by modulating the IGF-1 pathway. Plasma IGF-1 levels correlate with body weight and htt levels in the transgenic YAC mice expressing human htt. The effect of htt on IGF-1 expression is independent of CAG size. No effect on body weight is observed in transgenic YAC mice expressing...... and decreases the body weight of YAC128 animals to WT levels. Furthermore, given the ubiquitous expression of IGF-1 within the central nervous system, we also examined the impact of FL htt levels on IGF-1 expression in different regions of the brain, including the striatum, cerebellum of YAC18, YAC128...

  2. Normal aging modulates the neurotoxicity of mutant huntingtin.

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    Elsa Diguet

    Full Text Available Aging likely plays a role in neurodegenerative disorders. In Huntington's disease (HD, a disorder caused by an abnormal expansion of a polyglutamine tract in the protein huntingtin (Htt, the role of aging is unclear. For a given tract length, the probability of disease onset increases with age. There are mainly two hypotheses that could explain adult onset in HD: Either mutant Htt progressively produces cumulative defects over time or "normal" aging renders neurons more vulnerable to mutant Htt toxicity. In the present study, we directly explored whether aging affected the toxicity of mutant Htt in vivo. We studied the impact of aging on the effects produced by overexpression of an N-terminal fragment of mutant Htt, of wild-type Htt or of a beta-Galactosidase (beta-Gal reporter gene in the rat striatum. Stereotaxic injections of lentiviral vectors were performed simultaneously in young (3 week and old (15 month rats. Histological evaluation at different time points after infection demonstrated that the expression of mutant Htt led to pathological changes that were more severe in old rats, including an increase in the number of small Htt-containing aggregates in the neuropil, a greater loss of DARPP-32 immunoreactivity and striatal neurons as assessed by unbiased stereological counts.The present results support the hypothesis that "normal" aging is involved in HD pathogenesis, and suggest that age-related cellular defects might constitute potential therapeutic targets for HD.

  3. The mTOR kinase inhibitor Everolimus decreases S6 kinase phosphorylation but fails to reduce mutant huntingtin levels in brain and is not neuroprotective in the R6/2 mouse model of Huntington's disease

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    Frentzel Stefan

    2010-06-01

    Full Text Available Abstract Background Huntington's disease (HD is a progressive neurodegenerative disorder caused by a CAG repeat expansion within the huntingtin gene. Mutant huntingtin protein misfolds and accumulates within neurons where it mediates its toxic effects. Promoting mutant huntingtin clearance by activating macroautophagy is one approach for treating Huntington's disease (HD. In this study, we evaluated the mTOR kinase inhibitor and macroautophagy promoting drug everolimus in the R6/2 mouse model of HD. Results Everolimus decreased phosphorylation of the mTOR target protein S6 kinase indicating brain penetration. However, everolimus did not activate brain macroautophagy as measured by LC3B Western blot analysis. Everolimus protected against early declines in motor performance; however, we found no evidence for neuroprotection as determined by brain pathology. In muscle but not brain, everolimus significantly decreased soluble mutant huntingtin levels. Conclusions Our data suggests that beneficial behavioral effects of everolimus in R6/2 mice result primarily from effects on muscle. Even though everolimus significantly modulated its target brain S6 kinase, this did not decrease mutant huntingtin levels or provide neuroprotection.

  4. SUMO-2 and PIAS1 Modulate Insoluble Mutant Huntingtin Protein Accumulation

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    Jacqueline Gire O’Rourke

    2013-07-01

    Full Text Available A key feature in Huntington disease (HD is the accumulation of mutant Huntingtin (HTT protein, which may be regulated by posttranslational modifications. Here, we define the primary sites of SUMO modification in the amino-terminal domain of HTT, show modification downstream of this domain, and demonstrate that HTT is modified by the stress-inducible SUMO-2. A systematic study of E3 SUMO ligases demonstrates that PIAS1 is an E3 SUMO ligase for both HTT SUMO-1 and SUMO-2 modification and that reduction of dPIAS in a mutant HTT Drosophila model is protective. SUMO-2 modification regulates accumulation of insoluble HTT in HeLa cells in a manner that mimics proteasome inhibition and can be modulated by overexpression and acute knockdown of PIAS1. Finally, the accumulation of SUMO-2-modified proteins in the insoluble fraction of HD postmortem striata implicates SUMO-2 modification in the age-related pathogenic accumulation of mutant HTT and other cellular proteins that occurs during HD progression.

  5. Unbiased gene expression analysis implicates the huntingtin polyglutamine tract in extra-mitochondrial energy metabolism.

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    Jong-Min Lee

    2007-08-01

    Full Text Available The Huntington's disease (HD CAG repeat, encoding a polymorphic glutamine tract in huntingtin, is inversely correlated with cellular energy level, with alleles over approximately 37 repeats leading to the loss of striatal neurons. This early HD neuronal specificity can be modeled by respiratory chain inhibitor 3-nitropropionic acid (3-NP and, like 3-NP, mutant huntingtin has been proposed to directly influence the mitochondrion, via interaction or decreased PGC-1alpha expression. We have tested this hypothesis by comparing the gene expression changes due to mutant huntingtin accurately expressed in STHdh(Q111/Q111 cells with the changes produced by 3-NP treatment of wild-type striatal cells. In general, the HD mutation did not mimic 3-NP, although both produced a state of energy collapse that was mildly alleviated by the PGC-1alpha-coregulated nuclear respiratory factor 1 (Nrf-1. Moreover, unlike 3-NP, the HD CAG repeat did not significantly alter mitochondrial pathways in STHdh(Q111/Q111 cells, despite decreased Ppargc1a expression. Instead, the HD mutation enriched for processes linked to huntingtin normal function and Nf-kappaB signaling. Thus, rather than a direct impact on the mitochondrion, the polyglutamine tract may modulate some aspect of huntingtin's activity in extra-mitochondrial energy metabolism. Elucidation of this HD CAG-dependent pathway would spur efforts to achieve energy-based therapeutics in HD.

  6. Detection of ubiquitinated huntingtin species in intracellular aggregates

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    Katrin eJuenemann

    2015-01-01

    Full Text Available Protein conformation diseases, including polyglutamine diseases, result from the accumulation and aggregation of misfolded proteins. Huntington’s disease is one of nine diseases caused by an expanded polyglutamine repeat within the affected protein and is hallmarked by intracellular inclusion bodies composed of aggregated N-terminal huntingtin fragments and other sequestered proteins. Fluorescence microscopy and filter trap assay are conventional methods to study protein aggregates, but cannot be used to analyze the presence and levels of post-translational modifications of aggregated huntingtin such as ubiquitination. Ubiquitination of proteins can be a signal for degradation and intracellular localization, but also affects protein activity and protein-protein interactions. The function of ubiquitination relies on its mono- and polymeric isoforms attached to protein substrates. Studying the ubiquitination pattern of aggregated huntingtin fragments offers an important possibility to understand huntingtin degradation and aggregation processes within the cell. For the identification of aggregated huntingtin and its ubiquitinated species, solubilization of the cellular aggregates is mandatory. Here we describe methods to identify post-translational modifications such as ubiquitination of aggregated mutant huntingtin. This approach is specifically described for use with mammalian cell culture and is suitable to study other disease-related proteins prone to aggregate.

  7. Dysregulation of gene expression in the striatum of BACHD rats expressing full-length mutant huntingtin and associated abnormalities on molecular and protein levels.

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    Yu-Taeger, Libo; Bonin, Michael; Stricker-Shaver, Janice; Riess, Olaf; Nguyen, Hoa Huu Phuc

    2017-05-01

    Huntington disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the gene coding for the huntingtin protein (HTT). Mutant HTT (mHTT) has been proposed to cause neuronal dysfunction and neuronal loss through multiple mechanisms. Transcriptional changes may be a core pathogenic feature of HD. Utilizing the Affymetrix platform we performed a genome-wide RNA expression analysis in two BACHD transgenic rat lines (TG5 and TG9) at 12 months of age, both of which carry full-length human mHTT but with different expression levels. By defining the threshold of significance at p < 0.01, we found 1608 genes and 871 genes differentially expressed in both TG5 and TG9 rats when compared to the wild type littermates, respectively. We only chose the highly up-/down-regulated genes for further analysis by setting an additional threshold of 1.5 fold change. Comparing gene expression profiles of human HD brains and BACHD rats revealed a high concordance in both functional and IPA (Ingenuity Pathway Analysis) canonical pathways relevant to HD. In addition, we investigated the causes leading to gene expression changes at molecular and protein levels in BACHD rats including the involvement of polyQ-containing transcription factors TATA box-binding protein (TBP), Sp1 and CBP as well as the chromatin structure. We demonstrate that the BACHD rat model recapitulates the gene expression changes of the human disease supporting its role as a preclinical research animal model. We also show for the first time that TFIID complex formation is reduced, while soluble TBP is increased in an HD model. This finding suggests that mHTT is a competitor instead of a recruiter of polyQ-containing transcription factors in the transcription process in HD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Huntingtin is critical both pre- and postsynaptically for long-term learning-related synaptic plasticity in Aplysia.

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    Yun-Beom Choi

    Full Text Available Patients with Huntington's disease exhibit memory and cognitive deficits many years before manifesting motor disturbances. Similarly, several studies have shown that deficits in long-term synaptic plasticity, a cellular basis of memory formation and storage, occur well before motor disturbances in the hippocampus of the transgenic mouse models of Huntington's disease. The autosomal dominant inheritance pattern of Huntington's disease suggests the importance of the mutant protein, huntingtin, in pathogenesis of Huntington's disease, but wild type huntingtin also has been shown to be important for neuronal functions such as axonal transport. Yet, the role of wild type huntingtin in long-term synaptic plasticity has not been investigated in detail. We identified a huntingtin homolog in the marine snail Aplysia, and find that similar to the expression pattern in mammalian brain, huntingtin is widely expressed in neurons and glial cells. Importantly the expression of mRNAs of huntingtin is upregulated by repeated applications of serotonin, a modulatory transmitter released during learning in Aplysia. Furthermore, we find that huntingtin expression levels are critical, not only in presynaptic sensory neurons, but also in the postsynaptic motor neurons for serotonin-induced long-term facilitation at the sensory-to-motor neuron synapse of the Aplysia gill-withdrawal reflex. These results suggest a key role for huntingtin in long-term memory storage.

  9. Inhibition of PIP4Kγ ameliorates the pathological effects of mutant huntingtin protein.

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    Al-Ramahi, Ismael; Panapakkam Giridharan, Sai Srinivas; Chen, Yu-Chi; Patnaik, Samarjit; Safren, Nathaniel; Hasegawa, Junya; de Haro, Maria; Wagner Gee, Amanda K; Titus, Steven A; Jeong, Hyunkyung; Clarke, Jonathan; Krainc, Dimitri; Zheng, Wei; Irvine, Robin F; Barmada, Sami; Ferrer, Marc; Southall, Noel; Weisman, Lois S; Botas, Juan; Marugan, Juan Jose

    2017-12-26

    The discovery of the causative gene for Huntington's disease (HD) has promoted numerous efforts to uncover cellular pathways that lower levels of mutant huntingtin protein (mHtt) and potentially forestall the appearance of HD-related neurological defects. Using a cell-based model of pathogenic huntingtin expression, we identified a class of compounds that protect cells through selective inhibition of a lipid kinase, PIP4Kγ. Pharmacological inhibition or knock-down of PIP4Kγ modulates the equilibrium between phosphatidylinositide (PI) species within the cell and increases basal autophagy, reducing the total amount of mHtt protein in human patient fibroblasts and aggregates in neurons. In two Drosophila models of Huntington's disease, genetic knockdown of PIP4K ameliorated neuronal dysfunction and degeneration as assessed using motor performance and retinal degeneration assays respectively. Together, these results suggest that PIP4Kγ is a druggable target whose inhibition enhances productive autophagy and mHtt proteolysis, revealing a useful pharmacological point of intervention for the treatment of Huntington's disease, and potentially for other neurodegenerative disorders.

  10. Mutant Huntingtin Gene-Dose Impacts on Aggregate Deposition, DARPP32 Expression and Neuroinflammation in HdhQ150 Mice

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    Young, Douglas; Mayer, Franziska; Vidotto, Nella; Schweizer, Tatjana; Berth, Ramon; Abramowski, Dorothee; Shimshek, Derya R.; van der Putten, P. Herman; Schmid, Peter

    2013-01-01

    Huntington's disease (HD) is an autosomal dominant, progressive and fatal neurological disorder caused by an expansion of CAG repeats in exon-1 of the huntingtin gene. The encoded poly-glutamine stretch renders mutant huntingtin prone to aggregation. HdhQ150 mice genocopy a pathogenic repeat (∼150 CAGs) in the endogenous mouse huntingtin gene and model predominantly pre-manifest HD. Treating early is likely important to prevent or delay HD, and HdhQ150 mice may be useful to assess therapeutic strategies targeting pre-manifest HD. This requires appropriate markers and here we demonstrate, that pre-symptomatic HdhQ150 mice show several dramatic mutant huntingtin gene-dose dependent pathological changes including: (i) an increase of neuronal intra-nuclear inclusions (NIIs) in brain, (ii) an increase of extra-nuclear aggregates in dentate gyrus, (iii) a decrease of DARPP32 protein and (iv) an increase in glial markers of neuroinflammation, which curiously did not correlate with local neuronal mutant huntingtin inclusion-burden. HdhQ150 mice developed NIIs also in all retinal neuron cell-types, demonstrating that retinal NIIs are not specific to human exon-1 R6 HD mouse models. Taken together, the striking and robust mutant huntingtin gene-dose related changes in aggregate-load, DARPP32 levels and glial activation markers should greatly facilitate future testing of therapeutic strategies in the HdhQ150 HD mouse model. PMID:24086450

  11. Modulating the level of components within plants

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    Bobzin, Steven Craig; Apuya, Nestor; Chiang, Karen; Doukhanina, Elena; Feldmann, Kenneth; Jankowski, Boris; Margolles-Clark, Emilio; Mumenthaler, Daniel; Okamuro, Jack; Park, Joon-Hyun; Van Fleet, Jennifer E.; Zhang, Ke

    2017-09-12

    Materials and Methods for identifying lignin regulatory region-regulatory protein associations are disclosed. Materials and methods for modulating lignin accumulation are also disclosed. In addition, methods and materials for modulating (e.g., increasing or decreasing) the level of a component (e.g., protein, oil, lignin, carbon, a carotenoid, or a triterpenoid) in plants are disclosed.

  12. Binaural processing of modulated interaural level differences

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    Thompson, Eric Robert; Dau, Torsten

    2008-01-01

    Two experiments are presented that measure the acuity of binaural processing of modulated interaural level differences ILDs using psychoacoustic methods. In both experiments, dynamic ILDs were created by imposing an interaurally antiphasic sinusoidal amplitude modulation AM signal on high...... frequency, broadly tuned, bandpass-shaped patterns were obtained. Simulations with an existing binaural model show that a low-pass filter to limit the binaural temporal resolution is not sufficient to predict the results of the experiments....

  13. Onjisaponin B derived from Radix Polygalae enhances autophagy and accelerates the degradation of mutant α-synuclein and huntingtin in PC-12 cells.

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    Wu, An-Guo; Wong, Vincent Kam-Wai; Xu, Su-Wei; Chan, Wai-Kit; Ng, Choi-In; Liu, Liang; Law, Betty Yuen-Kwan

    2013-11-15

    Emerging evidence indicates important protective roles being played by autophagy in neurodegenerative disorders through clearance of aggregate-prone or mutant proteins. In the current study, we aimed to identify autophagy inducers from Chinese medicinal herbs as a potential neuroprotective agent that enhances the clearance of mutant huntingtin and α-synuclein in PC-12 cells. Through intensive screening using the green fluorescent protein-light chain 3 (GFP-LC3) autophagy detection platform, we found that the ethanol extracts of Radix Polygalae (Yuan Zhi) were capable of inducing autophagy. Further investigation showed that among three single components derived from Radix Polygalae--i.e., polygalacic acid, senegenin and onjisaponin B--onjisaponin B was able to induce autophagy and accelerate both the removal of mutant huntingtin and A53T α-synuclein, which are highly associated with Huntington disease and Parkinson disease, respectively. Our study further demonstrated that onjisaponin B induces autophagy via the AMPK-mTOR signaling pathway. Therefore, findings in the current study provide detailed insights into the protective mechanism of a novel autophagy inducer, which is valuable for further investigation as a new candidate agent for modulating neurodegenerative disorders through the reduction of toxicity and clearance of mutant proteins in the cellular level.

  14. Antisense downregulation of mutant huntingtin in a cell model

    DEFF Research Database (Denmark)

    Hasholt, L.; Abell, K.; Norremolle, A.

    2003-01-01

    or by addition to the culture medium. Results Expression of the fusion protein containing the mutant huntingtin fragment resulted in diffuse green fluorescence in the cytoplasm and formation of aggregates in some of the NT2 cells and NT2-N neurons. We obtained antisense sequence-specific inhibition of expression...... of the fusion protein and/or suppression of the aggregate formation in both cell types. In the NT2 cells the antisense effect was dependent on the way of administration of the oligo. Conclusions The PS-antisense oligo is effective in downregulation of mutant huntingtin, and the reduction of aggregate formation...... is a sensitive biological marker. The findings suggest that antisense knockdown of huntingtin could be a useful strategy for treatment of HD, and could also be suitable for studies of the normal and pathological function of huntingtin in different cellular model systems....

  15. Modularity for Modulating Exercises and Levels

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    Lund, Henrik Hautop; Nielsen, Camilla Balslev

    2011-01-01

    The modular interactive tiles aim at engaging anybody (elderly, carer, hospital personnel, children) in performing playful and motivating physical activities. Inspired by modular robotics, each tile is a self-contained module with processing power and communication to neighbouring modules....... In this paper, we investigate the therapeutic use. We show how the tiles are tested extensively with cardiac patients, COLD patients and stroke patients in hospitals and in the private homes of patients and elderly. We find that therapists are using the modular aspect of the tiles for personalized training...

  16. Mutated Huntingtin Causes Testicular Pathology in Transgenic Minipig Boars

    Czech Academy of Sciences Publication Activity Database

    Mačáková, Monika; Bohuslavová, Božena; Vochozková, Petra; Pavlok, Antonín; Sedláčková, M.; Vidinská, Daniela; Vochyánová, Klára; Lišková, Irena; Valeková, Ivona; Baxa, Monika; Ellederová, Zdeňka; Klíma, Jiří; Juhás, Štefan; Juhásová, Jana; Kloučková, J.; Haluzík, M.; Klempíř, J.; Hansíková, H.; Spáčilová, J.; Collins, R.; Blumenthal, I.; Talkowski, M.; Gusella, J. F.; Howland, D. S.; DiFiglia, M.; Motlík, Jan

    2016-01-01

    Roč. 16, 3-4 (2016), s. 245-259 ISSN 1660-2854 R&D Projects: GA MŠk ED2.1.00/03.0124; GA MŠk(CZ) LO1609; GA MŠk(CZ) 7F14308 Institutional support: RVO:67985904 Keywords : Huntington´s disease * pig model * mutant huntingtin Subject RIV: FH - Neurology Impact factor: 2.842, year: 2016

  17. Frequency of nuclear mutant huntingtin inclusion formation in neurons and glia is cell-type-specific

    NARCIS (Netherlands)

    Jansen, Anne H. P.; van Hal, Maurik; Op den Kelder, Ilse C.; Meier, Romy T.; de Ruiter, Anna-Aster; Schut, Menno H.; Smith, Donna L.; Grit, Corien; Brouwer, Nieske; Kamphuis, Willem; Boddeke, H. W. G. M.; den Dunnen, Wilfred F. A.; van Roon, Willeke M. C.; Bates, Gillian P.; Hol, Elly M.; Reits, Eric A.

    2017-01-01

    Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder that is caused by a CAG expansion in the Huntingtin (HTT) gene, leading to HTT inclusion formation in the brain. The mutant huntingtin protein (mHTT) is ubiquitously expressed and therefore nuclear inclusions

  18. Frequency of Nuclear Mutant Huntingtin Inclusion Formation in Neurons and Glia is Cell-Type-Specific

    NARCIS (Netherlands)

    Jansen, Anne H P; van Hal, Maurik; op den Kelder, Ilse C.; Meier, Romy T.; de Ruiter, Anna-Aster; Schut, Menno H.; Smith, Donna L.; Grit, Corien; Brouwer, Nieske; Kamphuis, Willem; Boddeke, H. W. G. M.; den Dunnen, Wilfred F. A.; van Roon, Willeke M. C.; Bates, Gillian P.; Hol, Elly M.; Reits, Eric A.

    Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder that is caused by a CAG expansion in the Huntingtin (HTT) gene, leading to HTT inclusion formation in the brain. The mutant huntingtin protein (mHTT) is ubiquitously expressed and therefore nuclear inclusions

  19. Functions of huntingtin in germ layer specification and organogenesis.

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    Giang D Nguyen

    Full Text Available Huntington's disease (HD is a neurodegenerative disease caused by abnormal polyglutamine expansion in the huntingtin protein (Htt. Although both Htt and the HD pathogenic mutation (mHtt are implicated in early developmental events, their individual involvement has not been adequately explored. In order to better define the developmental functions and pathological consequences of the normal and mutant proteins, respectively, we employed embryonic stem cell (ESC expansion, differentiation and induction experiments using huntingtin knock-out (KO and mutant huntingtin knock-in (Q111 mouse ESC lines. In KO ESCs, we observed impairments in the spontaneous specification and survival of ectodermal and mesodermal lineages during embryoid body formation and under inductive conditions using retinoic acid and Wnt3A, respectively. Ablation of BAX improves cell survival, but failed to correct defects in germ layer specification. In addition, we observed ensuing impairments in the specification and maturation of neural, hepatic, pancreatic and cardiomyocyte lineages. These developmental deficits occurred in concert with alterations in Notch, Hes1 and STAT3 signaling pathways. Moreover, in Q111 ESCs, we observed differential developmental stage-specific alterations in lineage specification and maturation. We also observed changes in Notch/STAT3 expression and activation. Our observations underscore essential roles of Htt in the specification of ectoderm, endoderm and mesoderm, in the specification of neural and non-neural organ-specific lineages, as well as cell survival during early embryogenesis. Remarkably, these developmental events are differentially deregulated by mHtt, raising the possibility that HD-associated early developmental impairments may contribute not only to region-specific neurodegeneration, but also to non-neural co-morbidities.

  20. Perturbation with intrabodies reveals that calpain cleavage is required for degradation of huntingtin exon 1.

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    Amber L Southwell

    2011-01-01

    Full Text Available Proteolytic processing of mutant huntingtin (mHtt, the protein that causes Huntington's disease (HD, is critical for mHtt toxicity and disease progression. mHtt contains several caspase and calpain cleavage sites that generate N-terminal fragments that are more toxic than full-length mHtt. Further processing is then required for the degradation of these fragments, which in turn, reduces toxicity. This unknown, secondary degradative process represents a promising therapeutic target for HD.We have used intrabodies, intracellularly expressed antibody fragments, to gain insight into the mechanism of mutant huntingtin exon 1 (mHDx-1 clearance. Happ1, an intrabody recognizing the proline-rich region of mHDx-1, reduces the level of soluble mHDx-1 by increasing clearance. While proteasome and macroautophagy inhibitors reduce turnover of mHDx-1, Happ1 is still able to reduce mHDx-1 under these conditions, indicating Happ1-accelerated mHDx-1 clearance does not rely on these processes. In contrast, a calpain inhibitor or an inhibitor of lysosomal pH block Happ1-mediated acceleration of mHDx-1 clearance. These results suggest that mHDx-1 is cleaved by calpain, likely followed by lysosomal degradation and this process regulates the turnover rate of mHDx-1. Sequence analysis identifies amino acid (AA 15 as a potential calpain cleavage site. Calpain cleavage of recombinant mHDx-1 in vitro yields fragments of sizes corresponding to this prediction. Moreover, when the site is blocked by binding of another intrabody, V(L12.3, turnover of soluble mHDx-1 in living cells is blocked.These results indicate that calpain-mediated removal of the 15 N-terminal AAs is required for the degradation of mHDx-1, a finding that may have therapeutic implications.

  1. Multi-stage decoding of multi-level modulation codes

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    Lin, Shu; Kasami, Tadao; Costello, Daniel J., Jr.

    1991-01-01

    Various types of multi-stage decoding for multi-level modulation codes are investigated. It is shown that if the component codes of a multi-level modulation code and types of decoding at various stages are chosen properly, high spectral efficiency and large coding gain can be achieved with reduced decoding complexity. Particularly, it is shown that the difference in performance between the suboptimum multi-stage soft-decision maximum likelihood decoding of a modulation code and the single-stage optimum soft-decision decoding of the code is very small, only a fraction of dB loss in signal to noise ratio at a bit error rate (BER) of 10(exp -6).

  2. A design of optical modulation system with pixel-level modulation accuracy

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    Zheng, Shiwei; Qu, Xinghua; Feng, Wei; Liang, Baoqiu

    2018-01-01

    Vision measurement has been widely used in the field of dimensional measurement and surface metrology. However, traditional methods of vision measurement have many limits such as low dynamic range and poor reconfigurability. The optical modulation system before image formation has the advantage of high dynamic range, high accuracy and more flexibility, and the modulation accuracy is the key parameter which determines the accuracy and effectiveness of optical modulation system. In this paper, an optical modulation system with pixel level accuracy is designed and built based on multi-points reflective imaging theory and digital micromirror device (DMD). The system consisted of digital micromirror device, CCD camera and lens. Firstly we achieved accurate pixel-to-pixel correspondence between the DMD mirrors and the CCD pixels by moire fringe and an image processing of sampling and interpolation. Then we built three coordinate systems and calculated the mathematic relationship between the coordinate of digital micro-mirror and CCD pixels using a checkerboard pattern. A verification experiment proves that the correspondence error is less than 0.5 pixel. The results show that the modulation accuracy of system meets the requirements of modulation. Furthermore, the high reflecting edge of a metal circular piece can be detected using the system, which proves the effectiveness of the optical modulation system.

  3. On decoding of multi-level MPSK modulation codes

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    Lin, Shu; Gupta, Alok Kumar

    1990-01-01

    The decoding problem of multi-level block modulation codes is investigated. The hardware design of soft-decision Viterbi decoder for some short length 8-PSK block modulation codes is presented. An effective way to reduce the hardware complexity of the decoder by reducing the branch metric and path metric, using a non-uniform floating-point to integer mapping scheme, is proposed and discussed. The simulation results of the design are presented. The multi-stage decoding (MSD) of multi-level modulation codes is also investigated. The cases of soft-decision and hard-decision MSD are considered and their performance are evaluated for several codes of different lengths and different minimum squared Euclidean distances. It is shown that the soft-decision MSD reduces the decoding complexity drastically and it is suboptimum. The hard-decision MSD further simplifies the decoding while still maintaining a reasonable coding gain over the uncoded system, if the component codes are chosen properly. Finally, some basic 3-level 8-PSK modulation codes using BCH codes as component codes are constructed and their coding gains are found for hard decision multistage decoding.

  4. The cryo-electron microscopy structure of huntingtin

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    Guo, Qiang; Bin Huang; Cheng, Jingdong; Seefelder, Manuel; Engler, Tatjana; Pfeifer, Günter; Oeckl, Patrick; Otto, Markus; Moser, Franziska; Maurer, Melanie; Pautsch, Alexander; Baumeister, Wolfgang; Fernández-Busnadiego, Rubén; Kochanek, Stefan

    2018-03-01

    Huntingtin (HTT) is a large (348 kDa) protein that is essential for embryonic development and is involved in diverse cellular activities such as vesicular transport, endocytosis, autophagy and the regulation of transcription. Although an integrative understanding of the biological functions of HTT is lacking, the large number of identified HTT interactors suggests that it serves as a protein-protein interaction hub. Furthermore, Huntington’s disease is caused by a mutation in the HTT gene, resulting in a pathogenic expansion of a polyglutamine repeat at the amino terminus of HTT. However, only limited structural information regarding HTT is currently available. Here we use cryo-electron microscopy to determine the structure of full-length human HTT in a complex with HTT-associated protein 40 (HAP40; encoded by three F8A genes in humans) to an overall resolution of 4 Å. HTT is largely α-helical and consists of three major domains. The amino- and carboxy-terminal domains contain multiple HEAT (huntingtin, elongation factor 3, protein phosphatase 2A and lipid kinase TOR) repeats arranged in a solenoid fashion. These domains are connected by a smaller bridge domain containing different types of tandem repeats. HAP40 is also largely α-helical and has a tetratricopeptide repeat-like organization. HAP40 binds in a cleft and contacts the three HTT domains by hydrophobic and electrostatic interactions, thereby stabilizing the conformation of HTT. These data rationalize previous biochemical results and pave the way for improved understanding of the diverse cellular functions of HTT.

  5. Impaired heat shock response in cells expressing full-length polyglutamine-expanded huntingtin.

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    Sidhartha M Chafekar

    Full Text Available The molecular mechanisms by which polyglutamine (polyQ-expanded huntingtin (Htt causes neurodegeneration in Huntington's disease (HD remain unclear. The malfunction of cellular proteostasis has been suggested as central in HD pathogenesis and also as a target of therapeutic interventions for the treatment of HD. We present results that offer a previously unexplored perspective regarding impaired proteostasis in HD. We find that, under non-stress conditions, the proteostatic capacity of cells expressing full length polyQ-expanded Htt is adequate. Yet, under stress conditions, the presence of polyQ-expanded Htt impairs the heat shock response, a key component of cellular proteostasis. This impaired heat shock response results in a reduced capacity to withstand the damage caused by cellular stress. We demonstrate that in cells expressing polyQ-expanded Htt the levels of heat shock transcription factor 1 (HSF1 are reduced, and, as a consequence, these cells have an impaired a heat shock response. Also, we found reduced HSF1 and HSP70 levels in the striata of HD knock-in mice when compared to wild-type mice. Our results suggests that full length, non-aggregated polyQ-expanded Htt blocks the effective induction of the heat shock response under stress conditions and may thus trigger the accumulation of cellular damage during the course of HD pathogenesis.

  6. Assembly of Huntingtin headpiece into α-helical bundles.

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    Ozgur, Beytullah; Sayar, Mehmet

    2017-05-24

    Protein aggregation is a hallmark of neurodegenerative disorders. In this group of brain-related disorders, a disease-specific "host" protein or fragment misfolds and adopts a metastatic, aggregate-prone conformation. Often, this misfolded conformation is structurally and thermodynamically different from its native state. Intermolecular contacts, which arise in this non-native state, promote aggregation. In this regard, understanding the molecular principles and mechanisms that lead to the formation of such a non-native state and further promote the formation of the critical nucleus for fiber growth is essential. In this study, the authors analyze the aggregation propensity of Huntingtin headpiece (htt NT ), which is known to facilitate the polyQ aggregation, in relation to the helix mediated aggregation mechanism proposed by the Wetzel group. The authors demonstrate that even though htt NT displays a degenerate conformational spectrum on its own, interfaces of macroscopic or molecular origin can promote the α-helix conformation, eliminating all other alternatives in the conformational phase space. Our findings indicate that htt NT molecules do not have a strong orientational preference for parallel or antiparallel orientation of the helices within the aggregate. However, a parallel packed bundle of helices would support the idea of increased polyglutamine concentration, to pave the way for cross-β structures.

  7. Personalising e-learning modules: targeting Rasmussen levels using XML.

    Science.gov (United States)

    Renard, J M; Leroy, S; Camus, H; Picavet, M; Beuscart, R

    2003-01-01

    The development of Internet technologies has made it possible to increase the number and the diversity of on-line resources for teachers and students. Initiatives like the French-speaking Virtual Medical University Project (UMVF) try to organise the access to these resources. But both teachers and students are working on a partly redundant subset of knowledge. From the analysis of some French courses we propose a model for knowledge organisation derived from Rasmussen's stepladder. In the context of decision-making Rasmussen has identified skill-based, rule-based and knowledge-based levels for the mental process. In the medical context of problem-solving, we apply these three levels to the definition of three students levels: beginners, intermediate-level learners, experts. Based on our model, we build a representation of the hierarchical structure of data using XML language. We use XSLT Transformation Language in order to filter relevant data according to student level and to propose an appropriate display on students' terminal. The model and the XML implementation we define help to design tools for building personalised e-learning modules.

  8. Preventing mutant huntingtin proteolysis and intermittent fasting promote autophagy in models of Huntington disease.

    Science.gov (United States)

    Ehrnhoefer, Dagmar E; Martin, Dale D O; Schmidt, Mandi E; Qiu, Xiaofan; Ladha, Safia; Caron, Nicholas S; Skotte, Niels H; Nguyen, Yen T N; Vaid, Kuljeet; Southwell, Amber L; Engemann, Sabine; Franciosi, Sonia; Hayden, Michael R

    2018-03-06

    Huntington disease (HD) is caused by the expression of mutant huntingtin (mHTT) bearing a polyglutamine expansion. In HD, mHTT accumulation is accompanied by a dysfunction in basal autophagy, which manifests as specific defects in cargo loading during selective autophagy. Here we show that the expression of mHTT resistant to proteolysis at the caspase cleavage site D586 (C6R mHTT) increases autophagy, which may be due to its increased binding to the autophagy adapter p62. This is accompanied by faster degradation of C6R mHTT in vitro and a lack of mHTT accumulation the C6R mouse model with age. These findings may explain the previously observed neuroprotective properties of C6R mHTT. As the C6R mutation cannot be easily translated into a therapeutic approach, we show that a scheduled feeding paradigm is sufficient to lower mHTT levels in YAC128 mice expressing cleavable mHTT. This is consistent with a previous model, where the presence of cleavable mHTT impairs basal autophagy, while fasting-induced autophagy remains functional. In HD, mHTT clearance and autophagy may become increasingly impaired as a function of age and disease stage, because of gradually increased activity of mHTT-processing enzymes. Our findings imply that mHTT clearance could be enhanced by a regulated dietary schedule that promotes autophagy.

  9. Levels of conflict in reasoning modulate right lateral prefrontal cortex.

    Science.gov (United States)

    Stollstorff, Melanie; Vartanian, Oshin; Goel, Vinod

    2012-01-05

    Right lateral prefrontal cortex (rlPFC) has previously been implicated in logical reasoning under conditions of conflict. A functional magnetic resonance imaging (fMRI) study was conducted to explore its role in conflict more precisely. Specifically, we distinguished between belief-logic conflict and belief-content conflict, and examined the role of rlPFC under each condition. The results demonstrated that a specific region of rlPFC is consistently activated under both types of conflict. Moreover, the results of a parametric analysis demonstrated that the same region was modulated by the level of conflict contained in reasoning arguments. This supports the idea that this specific region is engaged to resolve conflict, including during deductive reasoning. This article is part of a Special Issue entitled "The Cognitive Neuroscience of Thought". Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Analysis of Harmonic Injection to the Modulation of Multi-Level ...

    African Journals Online (AJOL)

    This paper explores the analysis of third and ninth harmonic injection to the modulation of a multilevel diode clamped converter (DCC) at a varying modulation index. The spectral distributions of the various multi-level waveforms obtained under normal modulation index of 0.8 and over modulation index of 1.15 were ...

  11. Module-level DC/DC conversion for photovoltaic systems

    NARCIS (Netherlands)

    Bergveld, H.J.; Büthker, D.; Castello, C.; Doorn, T.S.; Jong, de A.; van Otten, R.; Waal, de K.

    2011-01-01

    Photovoltaic (PV) systems are increasingly used to generate electrical energy from solar irradiance incident on PV modules. Each PV module is formed by placing a large amount of PV cells, typically 60, in series. The PV system is then formed by placing a number, typically 10–12, of PV modules in

  12. The Circuit-Level Decoupling Modulation Strategy for Three-Level Neutral-Point-Clamped (TL-NPC) Inverter

    DEFF Research Database (Denmark)

    Zhang, Zhe; Thomsen, Ole Cornelius; Andersen, Michael A. E.

    2011-01-01

    In this paper, a circuit-level decoupling modulation strategy is proposed for the three-level (TL) neutral-point-clamped (NPC) inverters. With the proposed modulation scheme, the TL-NPC inverter can be decoupled into two three-level Buck converters in each defined operating section, which makes...

  13. Space Vector Pulse Width Modulation of a Multi-Level Diode ...

    African Journals Online (AJOL)

    Space Vector Pulse Width Modulation of a Multi-Level Diode Clamped ... of MATLAB /SIMULINK modeling of the space vector pulse-width modulation and the ... two adjacent active vectors in determining the switching process of the multilevel ...

  14. Modulation detection as a function of carrier frequency and level

    NARCIS (Netherlands)

    Fassel, R.; Kohlrausch, A.G.

    1995-01-01

    This paper describes recent experiments investigating temporal processing in the auditory system. Subjects had to discriminate sinusoidal signals with a flat temporal envelope from those with a sinusoidal amplitude modulation. The modulation depth at threshold was measured for a wide range of

  15. Huntingtin interacting proteins are genetic modifiers of neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Linda S Kaltenbach

    2007-05-01

    Full Text Available Huntington's disease (HD is a fatal neurodegenerative condition caused by expansion of the polyglutamine tract in the huntingtin (Htt protein. Neuronal toxicity in HD is thought to be, at least in part, a consequence of protein interactions involving mutant Htt. We therefore hypothesized that genetic modifiers of HD neurodegeneration should be enriched among Htt protein interactors. To test this idea, we identified a comprehensive set of Htt interactors using two complementary approaches: high-throughput yeast two-hybrid screening and affinity pull down followed by mass spectrometry. This effort led to the identification of 234 high-confidence Htt-associated proteins, 104 of which were found with the yeast method and 130 with the pull downs. We then tested an arbitrary set of 60 genes encoding interacting proteins for their ability to behave as genetic modifiers of neurodegeneration in a Drosophila model of HD. This high-content validation assay showed that 27 of 60 orthologs tested were high-confidence genetic modifiers, as modification was observed with more than one allele. The 45% hit rate for genetic modifiers seen among the interactors is an order of magnitude higher than the 1%-4% typically observed in unbiased genetic screens. Genetic modifiers were similarly represented among proteins discovered using yeast two-hybrid and pull-down/mass spectrometry methods, supporting the notion that these complementary technologies are equally useful in identifying biologically relevant proteins. Interacting proteins confirmed as modifiers of the neurodegeneration phenotype represent a diverse array of biological functions, including synaptic transmission, cytoskeletal organization, signal transduction, and transcription. Among the modifiers were 17 loss-of-function suppressors of neurodegeneration, which can be considered potential targets for therapeutic intervention. Finally, we show that seven interacting proteins from among 11 tested were able to

  16. The role of polyglutamine expansion and protein context in disease-related huntingtin/lipid interactions

    Science.gov (United States)

    Burke, Kathleen Anne

    Huntington's Disease (HD) is a neurodegenerative disorder that is defined by the accumulation of nanoscale aggregates comprised of the huntingtin (htt) protein. Aggregation is directly caused by an expanded polyglutamine (polyQ) domain in htt, leading to a diverse population of aggregate species, such as oligomers, fibrils, and annular aggregates. Furthermore, the length of this polyQ domain is directly related to onset and severity of disease. The first 17 amino acids on the N-terminus (N17) and the polyproline domain on the C-terminal side of the polyQ domain have been shown to further modulate the aggregation process. Additionally, N17 appears to have lipid binding properties as htt interacts with a variety of membrane-containing structures present in cells, such as organelles, and interactions with these membrane surfaces may further modulate htt aggregation. To investigate the interaction between htt exon1 and lipid bilayers, in situ atomic force microscopy (AFM) was used to directly monitor the aggregation of htt exon1 constructs with varying Q-length (35Q, 46Q, 51Q, and myc- 53Q) or synthetic peptides with different polyQ domain flanking sequences (KK-Q35-KK, KK-Q 35-P10-KK, N17-Q35-KK, and N 17-Q35-P10-KK) on supported lipid membranes comprised of total brain lipid extract. The exon1 fragments accumulated on the lipid membranes, causing disruption of the membrane, in a polyQ dependent manner. By adding N-terminal tags to the htt exon1 fragments, the interaction with the lipid bilayer was impeded. The KK-Q35-KK and KK-Q 35-P10-KK peptides had no appreciable interaction with lipid bilayers. Interestingly, polyQ peptides with the N17 flanking sequence interacted with the bilayer. N17-Q35-KK formed discrete aggregates on the bilayer, but there was minimal membrane disruption. The N17-Q35-P10-KK peptide interacted more aggressively with the lipid bilayer in a manner reminiscent of the htt exon1 proteins.

  17. 47 CFR 73.1570 - Modulation levels: AM, FM, TV and Class A TV aural.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Modulation levels: AM, FM, TV and Class A TV... levels: AM, FM, TV and Class A TV aural. (a) The percentage of modulation is to be maintained at as high a level as is consistent with good quality of transmission and good broadcast service, with maximum...

  18. Electromagnetic Cell Level Calibration for ATLAS Tile Calorimeter Modules

    CERN Document Server

    Kulchitskii, Yu A; Budagov, Yu A; Khubua, J I; Rusakovitch, N A; Vinogradov, V B; Henriques, A; Davidek, T; Tokar, S; Solodkov, A; Vichou, I

    2006-01-01

    We have determined the electromagnetic calibration constants of 11% TileCal modules exposed to electron beams with incident angles of 20 and 90 degrees. The gain of all the calorimeter cells have been pre-equalized using the radioactive Cs-source that will be also used in situ. The average values for these modules are equal to: for the flat filter method 1.154+/-0.002 pC/GeV and 1.192+/-0.002 pC/GeV for 20 and 90 degrees, for the fit method 1.040+/-0.002 pC/GeV and 1.068+/-0.003 pC/GeV, respectively. These average values for all cells of calibrated modules agree with the weighted average calibration constants for separate modules within the errors. Using the individual calibration constants for every module the RMS spread value of constants will be 1.9+/-0.1 %. In the case of the global constant this value will be 2.6+/-0.1 %. Finally, we present the global constants which should be used for the electromagnetic calibration of the ATLAS Tile hadronic calorimeter data in the ATHENA framework. These constants ar...

  19. The common inhaled anesthetic isoflurane increases aggregation of huntingtin and alters calcium homeostasis in a cell model of Huntington's disease

    International Nuclear Information System (INIS)

    Wang Qiujun; Liang Ge; Yang Hui; Wang Shouping; Eckenhoff, Maryellen F.; Wei Huafeng

    2011-01-01

    Isoflurane is known to increase β-amyloid aggregation and neuronal damage. We hypothesized that isoflurane will have similar effects on the polyglutamine huntingtin protein and will cause alterations in intracellular calcium homeostasis. We tested this hypothesis in striatal cells from the expanded glutamine huntingtin knock-in mouse (STHdh Q111/Q111 ) and wild type (STHdh Q7/Q7 ) striatal neurons. The primary cultured neurons were exposed for 24 h to equipotent concentrations of isoflurane, sevoflurane, and desflurane in the presence or absence of extracellular calcium and with or without xestospongin C, a potent endoplasmic reticulum inositol 1,4,5-trisphosphate (InsP 3 ) receptor antagonist. Aggregation of huntingtin protein, cell viability, and calcium concentrations were measured. Isoflurane, sevoflurane, and desflurane all increased the aggregation of huntingtin in STHdh Q111/Q111 cells, with isoflurane having the largest effect. Isoflurane induced greater calcium release from the ER and relatively more cell damage in the STHdh Q111/Q111 huntingtin cells than in the wild type STHdh Q7/Q7 striatal cells. However, sevoflurane and desflurane caused less calcium release from the ER and less cell damage. Xestospongin C inhibited the isoflurane-induced calcium release from the ER, aggregation of huntingtin, and cell damage in the STHdh Q111/Q111 cells. In summary, the Q111 form of huntingtin increases the vulnerability of striatal neurons to isoflurane neurotoxicity through combined actions on the ER IP 3 receptors. Calcium release from the ER contributes to the anesthetic induced huntingtin aggregation in STHdh Q111/Q111 striatal cells.

  20. The front-end (Level-0) electronics interface module for the LHCb RICH detectors

    Energy Technology Data Exchange (ETDEWEB)

    Adinolfi, M. [Sub-department of Particle Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford, OX1 3RH (United Kingdom); Bibby, J.H. [Sub-department of Particle Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford, OX1 3RH (United Kingdom); Brisbane, S. [Sub-department of Particle Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford, OX1 3RH (United Kingdom); Gibson, V. [Cavendish Laboratory, University of Cambridge, Madingley Road, Cambridge CB3 0HE (United Kingdom); Harnew, N. [Sub-department of Particle Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford, OX1 3RH (United Kingdom); Jones, M. [Sub-department of Particle Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford, OX1 3RH (United Kingdom); Libby, J. [Sub-department of Particle Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford, OX1 3RH (United Kingdom)]. E-mail: j.libby1@physics.ox.ac.uk; Powell, A. [Sub-department of Particle Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford, OX1 3RH (United Kingdom); Newby, C. [Sub-department of Particle Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford, OX1 3RH (United Kingdom); Rotolo, N. [Sub-department of Particle Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford, OX1 3RH (United Kingdom); Smale, N. [Sub-department of Particle Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford, OX1 3RH (United Kingdom); Somerville, L.; Sullivan, P.; Topp-Jorgensen, S. [Sub-department of Particle Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford, OX1 3RH (United Kingdom); Wotton, S. [Cavendish Laboratory, University of Cambridge, Madingley Road, Cambridge CB3 0HE (United Kingdom); Wyllie, K. [CERN, CH-1211, Geneva 23 (Switzerland)

    2007-03-11

    The front-end (Level-0) electronics interface module for the LHCb Ring Imaging Cherenkov (RICH) detectors is described. This module integrates the novel hybrid photon detectors (HPDs), which instrument the RICH detectors, to the LHCb trigger, data acquisition (DAQ) and control systems. The system operates at 40 MHz with a first-level trigger rate of 1 MHz. The module design is presented and results are given for both laboratory and beam tests.

  1. The front-end (Level-0) electronics interface module for the LHCb RICH detectors

    International Nuclear Information System (INIS)

    Adinolfi, M.; Bibby, J.H.; Brisbane, S.; Gibson, V.; Harnew, N.; Jones, M.; Libby, J.; Powell, A.; Newby, C.; Rotolo, N.; Smale, N.; Somerville, L.; Sullivan, P.; Topp-Jorgensen, S.; Wotton, S.; Wyllie, K.

    2007-01-01

    The front-end (Level-0) electronics interface module for the LHCb Ring Imaging Cherenkov (RICH) detectors is described. This module integrates the novel hybrid photon detectors (HPDs), which instrument the RICH detectors, to the LHCb trigger, data acquisition (DAQ) and control systems. The system operates at 40 MHz with a first-level trigger rate of 1 MHz. The module design is presented and results are given for both laboratory and beam tests

  2. Dose-Dependent Lowering of Mutant Huntingtin Using Antisense Oligonucleotides in Huntington Disease Patients.

    Science.gov (United States)

    van Roon-Mom, Willeke M C; Roos, Raymund A C; de Bot, Susanne T

    2018-04-01

    On December 11 of 2017, Ionis Pharmaceuticals published a press release announcing dose-dependent reductions of mutant huntingtin protein in their HTTRx Phase 1/2a study in Huntington disease (HD) patients. The results from this Ionis trial have gained much attention from the patient community and the oligonucleotide therapeutics field, since it is the first trial targeting the cause of HD, namely the mutant huntingtin protein, using antisense oligonucleotides (ASOs). The press release also states that the primary endpoints of the study (safety and tolerability) were met, but does not contain data. This news follows the approval of another therapeutic ASO nusinersen (trade name Spinraza) for a neurological disease, spinal muscular atrophy, by the U.S. Food and Drug Administration and European Medicines Agency, in 2016 and 2017, respectively. Combined, this offers hope for the development of the HTTRx therapy for HD patients.

  3. Expression of Huntingtons disease markers in the cornea of minipig transgenic for the human mutated huntingtin

    Czech Academy of Sciences Publication Activity Database

    Ardan, Taras; Juhás, Štefan; Motlík, Jan

    2013-01-01

    Roč. 91, č. 252 (2013), S016-S016 ISSN 1755-375X. [European Association for Vision and Eye Research EVER 2013. 18.09.2013-21.09.2013, Nice] R&D Projects: GA MŠk ED2.1.00/03.0124; GA TA ČR(CZ) TA01011466 Institutional support: RVO:67985904 Keywords : huntingtin Subject RIV: EB - Genetics ; Molecular Biology

  4. Modulation Methods for Three-level Neutral-Point-Clamped Inverter Achieving Stress Redistribution under Moderate Modulation Index

    DEFF Research Database (Denmark)

    Ma, Ke; Blaabjerg, Frede

    2016-01-01

    This letter investigates the loss and thermal behaviors of a three-level neutral-point-clamped (3L-NPC) inverter undergoing moderate modulation index, which is typically presented during minor voltage sags of the power grid or speed changes of the electric machines. A series of new space vector m...

  5. Understanding of phase modulation in two-level systems through inverse scattering

    International Nuclear Information System (INIS)

    Hasenfeld, A.; Hammes, S.L.; Warren, W.S.

    1988-01-01

    Analytical and numerical calculations describe the effects of shaped radiation pulses on two-level systems in terms of quantum-mechanical scattering. Previous results obtained in the reduced case of amplitude modulation are extended to the general case of simultaneous amplitude and phase modulation. We show that an infinite family of phase- and amplitude-modulated pulses all generate rectangular inversion profiles. Experimental measurements also verify the theoretical analysis

  6. Comparative Study on Atmospheric Dispersion Module of Level 3 PSA

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Dahye; Jang, Misuk; Kang, Hyun Sik; Kim, Seoung Rae [NESS, Daejeon (Korea, Republic of)

    2016-10-15

    Some regulation documents such as Regulatory Guides and NUREG publications from the U.S. Nuclear Regulatory Commission (NRC) have influences on domestic radiation environmental analyses. As renewal versions of NUREG-0800 and NUREG-1555 have issued lately, the assessment for Severe Accident (SA) with Probabilistic Safety Assessment (PSA) should be added to Safety Analysis Report (SAR) and Radiation Environmental Report (RER). Because these reports are the required documents for obtaining the construction permit and operating license, it is important to understand the PSA methodology and it needs to improve the site-specific input data of L3PSA codes for SA. First, our review focuses on the atmospheric dispersion and deposition related input data of L3PSA code in this paper. Then we will continue to review the improvements of other input data. Two atmospheric dispersion models, which are PAVAN developed for design basis accident and ATMOS of MACCS2 code developed for SA, were reviewed in this paper. L3PSA deals with the effects of severe accidents and basically includes the evaluation of both short- and long-term effects. Therefore, both the deposition effects and nuclide information(type, amount, and chemical characteristics of released radionuclide) would be considered as the input parameters of atmospheric dispersion model for L3PSA. Additionally, the meteorological data would be sampled randomly to meet the purpose of probabilistic method. However, the sampling method would be selected according to analysis purpose. After review, ATMOS module and its input data are suitably developed for the atmospheric dispersion analysis of L3PSA. However, ATMOS module was developed using the site-specific terrain and environment characteristics. For the domestic application, it needs to study the input data reflecting the Korean terrain and environment characteristics. It would be also continuously improved in response to the time- and site-specific changes of weather

  7. Chronic inflammation modulates ghrelin levels in humans and rats.

    Science.gov (United States)

    Otero, M; Nogueiras, R; Lago, F; Dieguez, C; Gomez-Reino, J J; Gualillo, O

    2004-03-01

    The aim of this work was to investigate whether changes in plasma ghrelin, the recently discovered 28-amino acid gastric hormone that regulates growth hormone (GH) secretion and energy homeostasis, occur during inflammation in adjuvant-induced arthritis (AA) in rats. For completeness, ghrelin plasma levels were measured in rheumatoid arthritis (RA) patients. AA was induced in male Lewis rats using Freund's complete adjuvant. Animals were monitored for weight and food intake, every 2 or 3 days, along all time-course experiments. Plasma ghrelin concentrations in 31 RA patients and 18 healthy controls, as well as in rats, were determined by a specific double-antibody radioimmunoassay. Gastric ghrelin mRNA expression was evaluated by northern blot analysis. Human GH and insulin-like growth factor (IGF)-1 were determined by quantitative chemiluminescence assay. Compared with controls, arthritic rats gained significantly (P Ghrelin plasma levels were significantly lower at day 7 after arthritis induction than in controls (AA 7 = 91.2 +/- 5.6 pg/ml vs controls = 124.75 +/- 5.9 pg/ml), but they recovered to control levels by day 15. RA patients had ghrelin plasma levels significantly lower than healthy controls (RA = 24.54 +/- 2.57 pg/ml vs 39.01 +/- 4.47 pg/ml of healthy controls; P = 0.0041). In AA, there is a compensatory variation of ghrelin levels that relates to body weight adjustments. Recovery of ghrelin levels in the latter stage suggests an adaptive response and may represent a compensatory mechanism under catabolic conditions. In RA patients, chronic imbalance in ghrelin levels suggests that this gastric hormone may participate, together with other factors, in alterations of metabolic status during inflammatory stress.

  8. Coherence modulation at the photon-counting level: A new scheme for secure communication

    International Nuclear Information System (INIS)

    Rhodes, William T; Boughanmi, Abdellatif; Moreno, Yezid Torres

    2016-01-01

    When operated at the photon-counting level, coherence modulation can provide quantifiably secure binary signal transmission between two entities, security being based on the nonclonability of photons. (paper)

  9. Potent and selective antisense oligonucleotides targeting single-nucleotide polymorphisms in the Huntington disease gene / allele-specific silencing of mutant huntingtin

    DEFF Research Database (Denmark)

    Carroll, Jeffrey B; Warby, Simon C; Southwell, Amber L

    2011-01-01

    Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG-expansion in the huntingtin gene (HTT) that results in a toxic gain of function in the mutant huntingtin protein (mHTT). Reducing the expression of mHTT is therefore an attractive therapy for HD. However, wild...

  10. Olfactory stimulation modulates the blood glucose level in rats.

    Science.gov (United States)

    Tsuji, Tadataka; Tanaka, Susumu; Bakhshishayan, Sanam; Kogo, Mikihiko; Yamamoto, Takashi

    2018-01-01

    In both humans and animals, chemosensory stimuli, including odors and tastes, induce a variety of physiologic and mental responses related to energy homeostasis, such as glucose kinetics. The present study examined the importance of olfactory function in glucose kinetics following ingestion behavior in a simplified experimental scenario. We applied a conventional glucose tolerance test to rats with and without olfactory function and analyzed subsequent blood glucose (BG) curves in detail. The loss of olfactory input due to experimental damage to the olfactory mucosa induced a marked decrease in the area under the BG curve. Exposure to grapefruit odor and its main component, limonene, both of which activate the sympathetic nerves, before glucose loading also greatly depressed the BG curve. Pre-loading exposure to lavender odor, a parasympathetic activator, stabilized the BG level. These results suggest that olfactory function is important for proper glucose kinetics after glucose intake and that certain fragrances could be utilized as tools for controlling BG levels.

  11. Modulation of Human Plasma Fibronectin Levels Following Exercise,

    Science.gov (United States)

    1988-01-01

    forms of this large molecular weight (440 kilodaltons) glycoprotein,(17. While the tissue type is cell-associated and important to cell adhesion and...increased under conditions of pathology, such as in obesity (6). cancer (3). proteinuria (4). diabetic retinopathy (5). and preeclampsia (27). in the absence...Res. 1977: 22:709-716. 27. Stubbs. T.M.. Lazarchick. J.. and Horger. E.O. Plasma fibronectin levels in preeclampsia : A possible biochemical marker

  12. Fitness Level Modulates Intraocular Pressure Responses to Strength Exercises.

    Science.gov (United States)

    Vera, Jesús; Jiménez, Raimundo; Redondo, Beatríz; Cárdenas, David; García-Ramos, Amador

    2018-06-01

    Purpose/Aim: The execution of strength exercises has demonstrated to increase the intraocular pressure (IOP) levels, and it may have a negative impact on the ocular health. We aimed to explore the influence of fitness level on the acute IOP response to strength exercises performed under different loading conditions, as well as to test whether the IOP responses differ between the bench press and jump squat when performed against the same relative loads. Forty military personnel males were divided in two subgroups (20 high-fit and 20 low-fit) based on their relative to body mass one-repetition maximum (1-RM). Participants performed an incremental loading test in the bench press and jump squat exercises, and IOP was assessed before and after each repetition by rebound tonometry. IOP increased immediately after executing both exercises (p e., high-fit and low-fit) and in both exercises (R 2 range: 0.81-1.00). Higher fitness level attenuated the IOP rise produced by both exercises (p < 0.01 in both cases). The bench press induced higher IOP increments than the jump squat for both groups at relative loads of ~50%1-RM and ~60%1-RM (p < 0.01 in all cases). These data indicate that IOP increases as a consequence of performing strength exercises, being the increment accentuated with the increase of the load and in the bench press compared to the jump squat exercise. Of special importance would be that the IOP responses were significantly reduced in high-fit individuals. These findings should be addressed in glaucoma patients.

  13. Space vector modulation strategy for neutral-point voltage balancing in three-level inverter systems

    DEFF Research Database (Denmark)

    Choi, Uimin; Lee, Kyo Beum

    2013-01-01

    This study proposes a space vector modulation (SVM) strategy to balance the neutral-point voltage of three-level inverter systems. The proposed method is implemented by combining conventional symmetric SVM with nearest three-vector (NTV) modulation. The conventional SVM is converted to NTV...... modulation by properly adding or subtracting a minimum gate-on time. In addition, using this method, the switching frequency is reduced and a decrease of switching loss would be yielded. The neutral-point voltage is balanced by the proposed SVM strategy without additional hardware or complex calculations....... Simulation and experimental results are shown to verify the validity and feasibility of the proposed SVM strategy....

  14. Multi-level trellis coded modulation and multi-stage decoding

    Science.gov (United States)

    Costello, Daniel J., Jr.; Wu, Jiantian; Lin, Shu

    1990-01-01

    Several constructions for multi-level trellis codes are presented and many codes with better performance than previously known codes are found. These codes provide a flexible trade-off between coding gain, decoding complexity, and decoding delay. New multi-level trellis coded modulation schemes using generalized set partitioning methods are developed for Quadrature Amplitude Modulation (QAM) and Phase Shift Keying (PSK) signal sets. New rotationally invariant multi-level trellis codes which can be combined with differential encoding to resolve phase ambiguity are presented.

  15. Spatial modulation of the Fermi level by coherent illumination of undoped GaAs

    Science.gov (United States)

    Nolte, D. D.; Olson, D. H.; Glass, A. M.

    1989-11-01

    The Fermi level in undoped GaAs has been modulated spatially by optically quenching EL2 defects. The spatial gradient of the Fermi level produces internal electric fields that are much larger than fields generated by thermal diffusion alone. The resulting band structure is equivalent to a periodic modulation-doped p-i-p structure of alternating insulating and p-type layers. The internal fields are detected via the electro-optic effect by the diffraction of a probe laser in a four-wave mixing geometry. The direct control of the Fermi level distinguishes this phenomenon from normal photorefractive behavior and introduces a novel nonlinear optical process.

  16. System Level Design of a Continuous-Time Delta-Sigma Modulator for Portable Ultrasound Scanners

    DEFF Research Database (Denmark)

    Llimos Muntal, Pere; Færch, Kjartan; Jørgensen, Ivan Harald Holger

    2015-01-01

    In this paper the system level design of a continuous-time ∆Σ modulator for portable ultrasound scanners is presented. The overall required signal-to-noise ratio (SNR) is derived to be 42 dB and the sampling frequency used is 320 MHz for an oversampling ratio of 16. In order to match these requir......, based on high-level VerilogA simulations, the performance of the ∆Σ modulator versus various block performance parameters is presented as trade-off curves. Based on these results, the block specifications are derived.......In this paper the system level design of a continuous-time ∆Σ modulator for portable ultrasound scanners is presented. The overall required signal-to-noise ratio (SNR) is derived to be 42 dB and the sampling frequency used is 320 MHz for an oversampling ratio of 16. In order to match...

  17. α-Synuclein and huntingtin exon 1 amyloid fibrils bind laterally to the cellular membrane.

    Science.gov (United States)

    Monsellier, Elodie; Bousset, Luc; Melki, Ronald

    2016-01-13

    Fibrillar aggregates involved in neurodegenerative diseases have the ability to spread from one cell to another in a prion-like manner. The underlying molecular mechanisms, in particular the binding mode of the fibrils to cell membranes, are poorly understood. In this work we decipher the modality by which aggregates bind to the cellular membrane, one of the obligatory steps of the propagation cycle. By characterizing the binding properties of aggregates made of α-synuclein or huntingtin exon 1 protein displaying similar composition and structure but different lengths to mammalian cells we demonstrate that in both cases aggregates bind laterally to the cellular membrane, with aggregates extremities displaying little or no role in membrane binding. Lateral binding to artificial liposomes was also observed by transmission electron microscopy. In addition we show that although α-synuclein and huntingtin exon 1 fibrils bind both laterally to the cellular membrane, their mechanisms of interaction differ. Our findings have important implications for the development of future therapeutic tools that aim to block protein aggregates propagation in the brain.

  18. TF.Learn: TensorFlow's High-level Module for Distributed Machine Learning

    OpenAIRE

    Tang, Yuan

    2016-01-01

    TF.Learn is a high-level Python module for distributed machine learning inside TensorFlow. It provides an easy-to-use Scikit-learn style interface to simplify the process of creating, configuring, training, evaluating, and experimenting a machine learning model. TF.Learn integrates a wide range of state-of-art machine learning algorithms built on top of TensorFlow's low level APIs for small to large-scale supervised and unsupervised problems. This module focuses on bringing machine learning t...

  19. ATLAS Level-1 Calorimeter Trigger Subsystem Tests of a Prototype Cluster Processor Module

    CERN Document Server

    Garvey, J; Apostologlou, P; Ay, C; Barnett, B M; Bauss, B; Brawn, I P; Bohm, C; Dahlhoff, A; Davis, A O; Edwards, J; Eisenhandler, E F; Gee, C N P; Gillman, A R; Hanke, P; Hellman, S; Hidévgi, A; Hillier, S J; Jakobs, K; Kluge, E E; Landon, M; Mahboubi, K; Mahout, G; Meier, K; Meshkov, P; Moye, T H; Mills, D; Moyse, E; Nix, O; Penno, K; Perera, V J O; Qian, W; Schmitt, K; Schäfer, U; Silverstein, S; Staley, R J; Thomas, J; Trefzger, T M; Watkins, P M; Watson, A; 9th Workshop On Electronics For LHC Experiments - LECC 2003

    2003-01-01

    The Level-1 Calorimeter Trigger consists of a Preprocessor (PP), a Cluster Processor (CP), and a Jet/Energy-sum Processor (JEP). The CP and JEP receive digitised trigger-tower data from the Preprocessor and produce trigger multiplicity and Region-of-Interest (RoI) information. The trigger will also provide intermediate results to the data acquisition (DAQ) system for monitoring and diagnostic purposes by using Readout Driver (ROD) Modules. The CP Modules (CPM) are designed to find isolated electron/photon and hadron/tau clusters in overlapping windows of trigger towers. Each pipelined CPM processes 8-bit data from a total of 128 trigger towers at each LHC crossing. Four full-specification prototypes of CPMs have been built and results of complete tests on individual boards will be presented. These modules were then integrated with other modules to build an ATLAS Level-1 Calorimeter Trigger subsystem test bench. Realtime data were exchanged between modules, and time-slice readout data were tagged and transferr...

  20. Building America Case Study: Photovoltaic Systems with Module-Level Power Electronics

    Energy Technology Data Exchange (ETDEWEB)

    2015-09-01

    Direct current (DC) power optimizers and microinverters (together known as module-level power electronics, or MLPE) are one of the fastest growing market segments in the solar industry. According to GTM Research in The Global PV Inverter Landscape 2015, over 55% of all residential photovoltaic (PV) installations in the United States used some form of MLPE in 2014.

  1. Robustness of MW-Level IGBT modules against gate oscillations under short circuit events

    DEFF Research Database (Denmark)

    Reigosa, Paula Diaz; Wu, Rui; Iannuzzo, Francesco

    2015-01-01

    The susceptibility of MW-level IGBT power modules to critical gate voltage oscillations during short circuit events has been evidenced experimentally. This paper proposes a sensitivity analysis method to better understand the oscillating behavior dependence on different operating conditions (i...... the oscillation phenomenon, as well as to further improve the device performance during short circuit....

  2. Polymer-based 2D/3D wafer level heterogeneous integration for SSL module

    NARCIS (Netherlands)

    Yuan, C.; Wei, J.; Ye, H.; Koh, S.; Harianto, S.; Nieuwenhof, M.A. van den; Zhang, G.Q.

    2012-01-01

    This paper demonstrates a heterogeneous integration of solid state lighting (SSL) module, including light source (LED) and driver/control components. Such integration has been realized by the polymer-based reconfigured wafer level package technologies and such structure has been prototyped and

  3. Discontinuous PWM Modulation Strategy with Circuit-Level Decoupling Concept of Three-Level Neutral-Point Clamped (NPC) Inverter

    DEFF Research Database (Denmark)

    Zhang, Zhe; Thomsen, Ole Cornelius; Andersen, Michael A. E.

    2013-01-01

    inverters, but also reduces the switching loss of the inverter along with an inherent neutral point (NP) voltage control. Based on a circuit-level decoupling concept, the NPC inverter can be decoupled into two three-level Buck converters in every defined operating section, and thereby the controller design...... can be reduced by one third. In order to explain the operation of this topology properly, the decoupling principle including the driving signal synthesis and the NP potential variation are analyzed in detail in this paper. Finally the viability and performance of the proposed modulation scheme...

  4. Modulation cues influence binaural masking-level difference in masking-pattern experiments.

    Science.gov (United States)

    Nitschmann, Marc; Verhey, Jesko L

    2012-03-01

    Binaural masking patterns show a steep decrease in the binaural masking-level difference (BMLD) when masker and signal have no frequency component in common. Experimental threshold data are presented together with model simulations for a diotic masker centered at 250 or 500 Hz and a bandwidth of 10 or 100 Hz masking a sinusoid interaurally in phase (S(0)) or in antiphase (S(π)). Simulations with a binaural model, including a modulation filterbank for the monaural analysis, indicate that a large portion of the decrease in the BMLD in remote-masking conditions may be due to an additional modulation cue available for monaural detection. © 2012 Acoustical Society of America

  5. Huntingtin gene repeat size variations affect risk of lifetime depression.

    Science.gov (United States)

    Gardiner, Sarah L; van Belzen, Martine J; Boogaard, Merel W; van Roon-Mom, Willeke M C; Rozing, Maarten P; van Hemert, Albert M; Smit, Johannes H; Beekman, Aartjan T F; van Grootheest, Gerard; Schoevers, Robert A; Oude Voshaar, Richard C; Roos, Raymund A C; Comijs, Hannie C; Penninx, Brenda W J H; van der Mast, Roos C; Aziz, N Ahmad

    2017-12-11

    Huntington disease (HD) is a severe neuropsychiatric disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the HTT gene. Although HD is frequently complicated by depression, it is still unknown to what extent common HTT CAG repeat size variations in the normal range could affect depression risk in the general population. Using binary logistic regression, we assessed the association between HTT CAG repeat size and depression risk in two well-characterized Dutch cohorts─the Netherlands Study of Depression and Anxiety and the Netherlands Study of Depression in Older Persons─including 2165 depressed and 1058 non-depressed persons. In both cohorts, separately as well as combined, there was a significant non-linear association between the risk of lifetime depression and HTT CAG repeat size in which both relatively short and relatively large alleles were associated with an increased risk of depression (β = -0.292 and β = 0.006 for the linear and the quadratic term, respectively; both P < 0.01 after adjustment for the effects of sex, age, and education level). The odds of lifetime depression were lowest in persons with a HTT CAG repeat size of 21 (odds ratio: 0.71, 95% confidence interval: 0.52 to 0.98) compared to the average odds in the total cohort. In conclusion, lifetime depression risk was higher with both relatively short and relatively large HTT CAG repeat sizes in the normal range. Our study provides important proof-of-principle that repeat polymorphisms can act as hitherto unappreciated but complex genetic modifiers of depression.

  6. Multi-stage decoding for multi-level block modulation codes

    Science.gov (United States)

    Lin, Shu

    1991-01-01

    In this paper, we investigate various types of multi-stage decoding for multi-level block modulation codes, in which the decoding of a component code at each stage can be either soft-decision or hard-decision, maximum likelihood or bounded-distance. Error performance of codes is analyzed for a memoryless additive channel based on various types of multi-stage decoding, and upper bounds on the probability of an incorrect decoding are derived. Based on our study and computation results, we find that, if component codes of a multi-level modulation code and types of decoding at various stages are chosen properly, high spectral efficiency and large coding gain can be achieved with reduced decoding complexity. In particular, we find that the difference in performance between the suboptimum multi-stage soft-decision maximum likelihood decoding of a modulation code and the single-stage optimum decoding of the overall code is very small: only a fraction of dB loss in SNR at the probability of an incorrect decoding for a block of 10(exp -6). Multi-stage decoding of multi-level modulation codes really offers a way to achieve the best of three worlds, bandwidth efficiency, coding gain, and decoding complexity.

  7. Modulation of C. elegans Touch Sensitivity Is Integrated at Multiple Levels

    Science.gov (United States)

    Chen, Xiaoyin

    2014-01-01

    Sensory systems can adapt to different environmental signals. Here we identify four conditions that modulate anterior touch sensitivity in Caenorhabditis elegans after several hours and demonstrate that such sensory modulation is integrated at multiple levels to produce a single output. Prolonged vibration involving integrin signaling directly sensitizes the touch receptor neurons (TRNs). In contrast, hypoxia, the dauer state, and high salt reduce touch sensitivity by preventing the release of long-range neuroregulators, including two insulin-like proteins. Integration of these latter inputs occurs at upstream neurohormonal cells and at the insulin signaling cascade within the TRNs. These signals and those from integrin signaling converge to modulate touch sensitivity by regulating AKT kinases and DAF-16/FOXO. Thus, activation of either the integrin or insulin pathways can compensate for defects in the other pathway. This modulatory system integrates conflicting signals from different modalities, and adapts touch sensitivity to both mechanical and non-mechanical conditions. PMID:24806678

  8. Modulation Schemes of Multi-phase Three-Level Z-Source Inverters

    DEFF Research Database (Denmark)

    Gao, F.; Loh, P.C.; Blaabjerg, Frede

    2007-01-01

    different modulation requirement and output performance. For clearly illustrating the detailed modulation process, time domain analysis instead of the traditional multi-dimensional space vector demonstration is assumed which reveals the right way to insert shoot-through durations in the switching sequence...... with minimal commutation count. Lastly, the theoretical findings are verified in Matlab/PLECS simulation and experimentally using constructed laboratory prototypes.......This paper investigates the modulation schemes of three-level multiphase Z-source inverters with either two Z-source networks or single Z-source network connected between the dc sources and inverter circuitry. With the proper offset added for achieving both desired four-leg operation and optimized...

  9. Photovoltaic Shading Testbed for Module-Level Power Electronics: 2016 Performance Data Update

    Energy Technology Data Exchange (ETDEWEB)

    Deline, Chris [National Renewable Energy Lab. (NREL), Golden, CO (United States); Meydbray, Jenya [PV Evolution Labs (PVEL), Davis, CA (United States); Donovan, Matt [PV Evolution Labs (PVEL), Davis, CA (United States)

    2016-09-01

    The 2012 NREL report 'Photovoltaic Shading Testbed for Module-Level Power Electronics' provides a standard methodology for estimating the performance benefit of distributed power electronics under partial shading conditions. Since the release of the report, experiments have been conducted for a number of products and for different system configurations. Drawing from these experiences, updates to the test and analysis methods are recommended. Proposed changes in data processing have the benefit of reducing the sensitivity to measurement errors and weather variability, as well as bringing the updated performance score in line with measured and simulated values of the shade recovery benefit of distributed PV power electronics. Also, due to the emergence of new technologies including sub-module embedded power electronics, the shading method has been extended to include power electronics that operate at a finer granularity than the module level. An update to the method is proposed to account for these emerging technologies that respond to shading differently than module-level devices. The partial shading test remains a repeatable test procedure that attempts to simulate shading situations as would be experienced by typical residential or commercial rooftop photovoltaic (PV) systems. Performance data for multiple products tested using this method are discussed, based on equipment from Enphase, Solar Edge, Maxim Integrated and SMA. In general, the annual recovery of shading losses from the module-level electronics evaluated is 25-35%, with the major difference between different trials being related to the number of parallel strings in the test installation rather than differences between the equipment tested. Appendix D data has been added in this update.

  10. Pulse width modulated buck-boost five-level current source inverters

    DEFF Research Database (Denmark)

    Blaabjerg, Frede; Gao, F.; Loh, P.C.

    2008-01-01

    , resulting in the natural balance of input current. For maintaining the normalized volt-sec average unchanged, the alternative phase opposition disposition (APOD) modulation scheme with typical gating signal mapping technique from voltage source inverter (VSI) to CSI can be assumed to control the five......This paper presents new five-level current source inverters (CSIs) with voltage/current buck-boost capability. Being different from the existing multilevel CSI, the proposed CSIs were first designed to regulate the flowing path of dc input current by controlling two additional active switches......-level buck-boost CSIs. Next by observing the hidden current charging path during inductive charging interval under APOD modulation, it is noted that the buck-boost five-level CSI can then be further modified with lesser active component without degrading output performance. To verify the theoretical findings...

  11. Women's hormone levels modulate the motivational salience of facial attractiveness and sexual dimorphism.

    Science.gov (United States)

    Wang, Hongyi; Hahn, Amanda C; Fisher, Claire I; DeBruine, Lisa M; Jones, Benedict C

    2014-12-01

    The physical attractiveness of faces is positively correlated with both behavioral and neural measures of their motivational salience. Although previous work suggests that hormone levels modulate women's perceptions of others' facial attractiveness, studies have not yet investigated whether hormone levels also modulate the motivational salience of facial characteristics. To address this issue, we investigated the relationships between within-subject changes in women's salivary hormone levels (estradiol, progesterone, testosterone, and estradiol-to-progesterone ratio) and within-subject changes in the motivational salience of attractiveness and sexual dimorphism in male and female faces. The motivational salience of physically attractive faces in general and feminine female faces, but not masculine male faces, was greater in test sessions where women had high testosterone levels. Additionally, the reward value of sexually dimorphic faces in general and attractive female faces, but not attractive male faces, was greater in test sessions where women had high estradiol-to-progesterone ratios. These results provide the first evidence that the motivational salience of facial attractiveness and sexual dimorphism is modulated by within-woman changes in hormone levels. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Hydrophobically Modified siRNAs Silence Huntingtin mRNA in Primary Neurons and Mouse Brain

    Directory of Open Access Journals (Sweden)

    Julia F Alterman

    2015-01-01

    Full Text Available Applications of RNA interference for neuroscience research have been limited by a lack of simple and efficient methods to deliver oligonucleotides to primary neurons in culture and to the brain. Here, we show that primary neurons rapidly internalize hydrophobically modified siRNAs (hsiRNAs added directly to the culture medium without lipid formulation. We identify functional hsiRNAs targeting the mRNA of huntingtin, the mutation of which is responsible for Huntington's disease, and show that direct uptake in neurons induces potent and specific silencing in vitro. Moreover, a single injection of unformulated hsiRNA into mouse brain silences Htt mRNA with minimal neuronal toxicity. Thus, hsiRNAs embody a class of therapeutic oligonucleotides that enable simple and straightforward functional studies of genes involved in neuronal biology and neurodegenerative disorders in a native biological context.

  13. Topological Design and Modulation Strategy for Buck-Boost Three-Level Inverters

    DEFF Research Database (Denmark)

    Gao, Feng; Loh, Poh Chiang; Teodorescu, Remus

    2009-01-01

    To date, designed topologies for dc-ac inversion with both voltage buck and boost capabilities are mainly focused on two-level circuitries with extensions to three-level possibilities left nearly unexplored. Contributing to this area of research, this paper presents the design of a number of viable...... can perform distinct five-level line voltage and three-level phase voltage switching by simply controlling the active switches located in the designed voltage boost section of the circuits. As a cost saving option, one active switch can further be removed from the voltage boost section of the circuits...... buck-boost threelevel inverters that can also support bidirectional power conversion. The proposed front-end circuitry is developed from the C´ ukderived buck-boost two-level inverter, and by using the "alternative phase opposition disposition" modulation scheme, the buck-boost three-level inverters...

  14. Synergistic effect of fluorination on molecular energy level modulation in highly efficient photovoltaic polymers.

    Science.gov (United States)

    Zhang, Maojie; Guo, Xia; Zhang, Shaoqing; Hou, Jianhui

    2014-02-01

    The synergistic effect of fluorination on molecular energy level modulation is realized by introducing fluorine atoms onto both the donor and the acceptor moieties in a D-A polymer, and as a result, the polymer solar cell device based on the trifluorinated polymer, PBT-3F, shows a high efficiency of 8.6%, under illumination of AM 1.5G, 100 mW cm(-) (2) . © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Different Forms of Huntingtin in the Most 
Affected Organs; Brain and Testes of Transgenic Minipigs

    Czech Academy of Sciences Publication Activity Database

    Vidinská, Daniela; Motlík, Jan; Ellederová, Zdeňka

    2015-01-01

    Roč. 78, Suppl 2 (2015), s. 66-69 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Disease s /3./. Liblice, 08.11.2015-10.11.2015] R&D Projects: GA MŠk ED2.1.00/03.0124; GA MŠk(CZ) 7F14308 Institutional support: RVO:67985904 Keywords : Huntington´s disease * transgenic minipig model * mutant huntingtin Subject RIV: FH - Neurology Impact factor: 0.209, year: 2015

  16. Achieving nonlinear optical modulation via four-wave mixing in a four-level atomic system

    Science.gov (United States)

    Li, Hai-Chao; Ge, Guo-Qin; Zubairy, M. Suhail

    2018-05-01

    We propose an accessible scheme for implementing tunable nonlinear optical amplification and attenuation via a synergetic mechanism of four-wave mixing (FWM) and optical interference in a four-level ladder-type atomic system. By constructing a cyclic atom-field interaction, we show that two reverse FWM processes can coexist via optical transitions in different branches. In the suitable input-field conditions, strong interference effects between the input fields and the generated FWM fields can be induced and result in large amplification and deep attenuation of the output fields. Moreover, such an optical modulation from enhancement to suppression can be controlled by tuning the relative phase. The quantum system can be served as a switchable optical modulator with potential applications in quantum nonlinear optics.

  17. Modulation of the sound press level by the treatment of polymer diaphragms through ion implantation method

    International Nuclear Information System (INIS)

    Yeo, Sunmog; Park, Jaewon; Lee, Hojae

    2010-01-01

    We present two different surface modification treatments, an ion implantation, and an ion beam mixing, and show that the surface modifications caused by these treatments are useful tools to modulate the sound press level. The ion implantations on various polymer diaphragms cause an increase in the resonant frequency so that the sound press level is lowered at low frequencies. On the contrary, a Cu or Fe 2 O 3 coating by using an ion beam mixing method causes a decrease in the resonant frequency, resulting in a high sound press level at low frequencies. We discuss the physical reasons for the change in the sound press level due to the ion-implantation methods.

  18. The data module, the missing link in high level control languages

    International Nuclear Information System (INIS)

    Crowley-Milling, M.C.

    1979-01-01

    In order to be able to use the full power and simplicity of a high level language for writing plant control programs, it must be possible to use the plant variables in the same manner as program variables, completely transparent to the address structure of the hardware and interface. Some of the high level languages provide facilities for writing procedures or subroutines to make this possible. However, most of the facilities provided share a number of disadvantages: they are usually relatively complicated for the user, involving passing many parameters which the programmer has to specify at each call; they usually have restrictions on the data types that can be used, and the data bases are normally organised to suit the interface system. However, the high level programmer is interested in the equipment to be controlled such as motors, pumps, power supplies, valves, etc., rather than the means of interfacing the equipment, and it greatly simplifies his task if he can call for actions on these items, using simple mnemonic names and a simple format. The design of the control system for the CERN 400 GeV proton accelerator, using a network of some thirty computers, provided the opportunity to try out a different approach, using an interpreter for the high-level control language NODAL, together with special functions which are called 'data modules'. The use of the data module and interpreter are described. (author)

  19. A RhABF2/Ferritin module affects rose (Rosa hybrida) petal dehydration tolerance and senescence by modulating iron levels.

    Science.gov (United States)

    Liu, Jitao; Fan, Youwei; Zou, Jing; Fang, Yiqun; Wang, Linghao; Wang, Meng; Jiang, Xinqiang; Liu, Yiqing; Gao, Junping; Zhang, Changqing

    2017-12-01

    Plants often develop the capacity to tolerate moderate and reversible environmental stresses, such as drought, and to re-establish normal development once the stress has been removed. An example of this phenomenon is provided by cut rose (Rosa hybrida) flowers, which experience typical reversible dehydration stresses during post-harvest handling after harvesting at the bud stages. The molecular mechanisms involved in rose flower dehydration tolerance are not known, however. Here, we characterized a dehydration- and abscisic acid (ABA)-induced ferritin gene (RhFer1). Dehydration-induced free ferrous iron (Fe 2+ ) is preferentially sequestered by RhFer1 and not transported outside of the petal cells, to restrict oxidative stresses during dehydration. Free Fe 2+ accumulation resulted in more serious oxidative stresses and the induction of genes encoding antioxidant enzyme in RhFer1-silenced petals, and poorer dehydration tolerance was observed compared with tobacco rattle virus (TRV) controls. We also determined that RhABF2, an AREB/ABF transcription factor involved in the ABA signaling pathway, can activate RhFer1 expression by directly binding to its promoter. The silencing of RhABF2 decreased dehydration tolerance and disrupted Fe homeostasis in rose petals during dehydration, as did the silencing of RhFer1. Although both RhFer1 and Fe transporter genes are induced during flower natural senescence in plants, the silencing of RhABF2 or RhFer1 accelerates the petal senescence processes. These results suggest that the regulatory module RhABF2/RhFer1 contributes to the maintenance of Fe levels and enhances dehydration tolerance through the action of RhFer1 locally sequestering free Fe 2+ under dehydration conditions, and plays synergistic roles with transporter genes during flower senescence. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  20. BACHD rats expressing full-length mutant huntingtin exhibit differences in social behavior compared to wild-type littermates.

    Science.gov (United States)

    Manfré, Giuseppe; Novati, Arianna; Faccini, Ilaria; Rossetti, Andrea C; Bosch, Kari; Molteni, Raffaella; Riva, Marco A; Van der Harst, Johanneke E; Nguyen, Huu Phuc; Homberg, Judith R

    2018-01-01

    Huntington disease (HD) is a devastating inherited neurodegenerative disorder characterized by progressive motor, cognitive, and psychiatric symptoms without any cure to slow down or stop the progress of the disease. The BACHD rat model for HD carrying the human full-length mutant huntingtin protein (mHTT) with 97 polyQ repeats has been recently established as a promising model which reproduces several HD-like features. While motor and cognitive functions have been characterized in BACHD rats, little is known about their social phenotype. This study focuses especially on social behavior since evidence for social disturbances exists in human patients. Our objective was to compare social behavior in BACHD and wild-type (WT) rats at different ages, using two different measures of sociability. Animals were tested longitudinally at the age of 2, 4 and 8 months in the social interaction test to examine different parameters of sociability. A separate cohort of 7 month old rats was tested in the three chamber social test to measure both sociability and social novelty. Gene expression analyses in 8 months old animals were performed by real time qRT-PCR to evaluate a potential involvement of D1 and D2 dopaminergic receptors and the contribution of Brain-derived neurotrophic factor (BDNF) to the observed behavioral alterations. In the social interaction test, BACHD rats showed age-dependent changes in behaviour when they were-re introduced to their cagemate after a 24 hours-period of individual housing. The time spent on nape attacks increased with aging. Furthermore, a significant higher level of pinning at 2 months of age was shown in the BACHD rats compared to wild-types, followed by a reduction at 4 and 8 months. On the other hand, BACHD rats exhibited a decreased active social behaviour compared to wild-types, reflected by genotype-effects on approaching, following and social nose contact. In the three chamber social test, BACHD rats seemed to show a mild deficit in

  1. BACHD rats expressing full-length mutant huntingtin exhibit differences in social behavior compared to wild-type littermates.

    Directory of Open Access Journals (Sweden)

    Giuseppe Manfré

    Full Text Available Huntington disease (HD is a devastating inherited neurodegenerative disorder characterized by progressive motor, cognitive, and psychiatric symptoms without any cure to slow down or stop the progress of the disease. The BACHD rat model for HD carrying the human full-length mutant huntingtin protein (mHTT with 97 polyQ repeats has been recently established as a promising model which reproduces several HD-like features. While motor and cognitive functions have been characterized in BACHD rats, little is known about their social phenotype.This study focuses especially on social behavior since evidence for social disturbances exists in human patients. Our objective was to compare social behavior in BACHD and wild-type (WT rats at different ages, using two different measures of sociability.Animals were tested longitudinally at the age of 2, 4 and 8 months in the social interaction test to examine different parameters of sociability. A separate cohort of 7 month old rats was tested in the three chamber social test to measure both sociability and social novelty. Gene expression analyses in 8 months old animals were performed by real time qRT-PCR to evaluate a potential involvement of D1 and D2 dopaminergic receptors and the contribution of Brain-derived neurotrophic factor (BDNF to the observed behavioral alterations.In the social interaction test, BACHD rats showed age-dependent changes in behaviour when they were-re introduced to their cagemate after a 24 hours-period of individual housing. The time spent on nape attacks increased with aging. Furthermore, a significant higher level of pinning at 2 months of age was shown in the BACHD rats compared to wild-types, followed by a reduction at 4 and 8 months. On the other hand, BACHD rats exhibited a decreased active social behaviour compared to wild-types, reflected by genotype-effects on approaching, following and social nose contact. In the three chamber social test, BACHD rats seemed to show a mild

  2. BACHD rats expressing full-length mutant huntingtin exhibit differences in social behavior compared to wild-type littermates

    Science.gov (United States)

    Manfré, Giuseppe; Novati, Arianna; Faccini, Ilaria; Rossetti, Andrea C.; Bosch, Kari; Molteni, Raffaella; Riva, Marco A.; Van der Harst, Johanneke E.; Homberg, Judith R.

    2018-01-01

    Background Huntington disease (HD) is a devastating inherited neurodegenerative disorder characterized by progressive motor, cognitive, and psychiatric symptoms without any cure to slow down or stop the progress of the disease. The BACHD rat model for HD carrying the human full-length mutant huntingtin protein (mHTT) with 97 polyQ repeats has been recently established as a promising model which reproduces several HD-like features. While motor and cognitive functions have been characterized in BACHD rats, little is known about their social phenotype. Objective This study focuses especially on social behavior since evidence for social disturbances exists in human patients. Our objective was to compare social behavior in BACHD and wild-type (WT) rats at different ages, using two different measures of sociability. Methods Animals were tested longitudinally at the age of 2, 4 and 8 months in the social interaction test to examine different parameters of sociability. A separate cohort of 7 month old rats was tested in the three chamber social test to measure both sociability and social novelty. Gene expression analyses in 8 months old animals were performed by real time qRT-PCR to evaluate a potential involvement of D1 and D2 dopaminergic receptors and the contribution of Brain-derived neurotrophic factor (BDNF) to the observed behavioral alterations. Results In the social interaction test, BACHD rats showed age-dependent changes in behaviour when they were-re introduced to their cagemate after a 24 hours-period of individual housing. The time spent on nape attacks increased with aging. Furthermore, a significant higher level of pinning at 2 months of age was shown in the BACHD rats compared to wild-types, followed by a reduction at 4 and 8 months. On the other hand, BACHD rats exhibited a decreased active social behaviour compared to wild-types, reflected by genotype-effects on approaching, following and social nose contact. In the three chamber social test, BACHD rats

  3. [Plasma IL-18 levels are related to insulin and are modulated by IL-18 gene polymorphisms].

    Science.gov (United States)

    Martinez-Hervas, Sergio; Martínez-Barquero, Vanesa; Nuñez Savall, Ester; Lendínez, Verónica; Olivares, Laura; Benito, Esther; Real, Jose T; Chaves, F Javier; Ascaso, Juan F

    2015-01-01

    Atherosclerosis is an inflammatory chronic disease influenced by multiple factors. Different prospective studies have shown that plasmatic levels of inflammatory markers were related to atherosclerosis and cardiovascular disease. To evaluate whether plasmatic levels of interleukin 18 (IL-18) are modulated by SNPs (single nucleotide polymorphisms) of the IL 18 gene and its possible association with insulin levels and other cardiovascular risk factors. 746 individuals were studied for a period of two years by opportunistic selection in the metropolitan area of Valencia. Parameters of lipid and glucose metabolism were analyzed by standard methodology. IL-18 was measured by ELISA. Individuals with insulin resistance showed significant higher levels of IL-18. IL 18 was significantly correlated with insulin levels and other cardiovascular risk factors. The CC genotype of the rs1834481 SNP was significantly associated with lower levels of IL-18. However, the GG genotype of the rs7559479 was associated with significant higher levels of IL-18. IL-18 is associated with insulin resistance and other cardiovascular risk factors, being those levels genetically regulated. Copyright © 2015 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  4. 4G/5G polymorphism modulates PAI-1 circulating levels in obese women.

    Science.gov (United States)

    Fernandes, Karla S; Sandrim, Valéria C

    2012-05-01

    The increase in plasminogen activator inhibitor type 1 (PAI-1) has been described as a risk factor to thrombosis-related diseases. In addition, it has been demonstrated that the variant 4G of polymorphism 4G/5G located in promoter region of PAI-1 gene is associated with higher PAI-1 levels. We investigate the role of this polymorphism on circulating PAI-1 concentration in a population of 57 obese women (23%, 4G/4G; 49%, 4G/5G and 28%, 5G/5G genotypes). Our results demonstrate a genotype-specific modulation on PAI-1 levels in obese women, thus 5G/5G genotype presented significantly lower levels of plasma PAI-1 when compared to 4G/4G group (46 ± 19 ng/mL vs. 63 ± 13 ng/mL, respectively). Our findings indicate that obese carriers of 4G/4G genotype may have increased risk to develop thrombotic diseases.

  5. Modulation of ROS levels in fibroblasts by altering mitochondria regulates the process of wound healing.

    Science.gov (United States)

    Janda, Jaroslav; Nfonsam, Valentine; Calienes, Fernanda; Sligh, James E; Jandova, Jana

    2016-05-01

    Mitochondria are the major source of reactive oxygen species (ROS) in fibroblasts which are thought to be crucial regulators of wound healing with a potential to affect the expression of nuclear genes involved in this process. ROS generated by mitochondria are involved in all stages of tissue repair process but the regulation of ROS-generating system in fibroblasts still remains poorly understood. The purpose of this study was to better understand molecular mechanisms of how the regulation of ROS levels generated by mitochondria may influence the process of wound repair. Cybrid model system of mtDNA variations was used to study the functional consequences of altered ROS levels on wound healing responses in a uniform nuclear background of cultured ρ(0) fibroblasts. Mitochondrial ROS in cybrids were modulated by antioxidants that quench ROS to examine their ability to close the wound. Real-time PCR arrays were used to investigate whether ROS generated by specific mtDNA variants have the ability to alter expression of some key nuclear-encoded genes central to the wound healing response and oxidative stress. Our data suggest levels of mitochondrial ROS affect expression of some nuclear encoded genes central to wound healing response and oxidative stress and modulation of mitochondrial ROS by antioxidants positively affects in vitro process of wound closure. Thus, regulation of mitochondrial ROS-generating system in fibroblasts can be used as effective natural redox-based strategy to help treat non-healing wounds.

  6. Dosimetric analysis of testicular doses in prostate intensity-modulated and volumetric-modulated arc radiation therapy at different energy levels

    Energy Technology Data Exchange (ETDEWEB)

    Onal, Cem, E-mail: hcemonal@hotmail.com; Arslan, Gungor; Dolek, Yemliha; Efe, Esma

    2016-01-01

    The aim of this study is to evaluate the incidental testicular doses during prostate radiation therapy with intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc radiotherapy (VMAT) at different energies. Dosimetric data of 15 patients with intermediate-risk prostate cancer who were treated with radiotherapy were analyzed. The prescribed dose was 78 Gy in 39 fractions. Dosimetric analysis compared testicular doses generated by 7-field intensity-modulated radiotherapy and volumetric-modulated arc radiotherapy with a single arc at 6, 10, and 15 MV energy levels. Testicular doses calculated from the treatment planning system and doses measured from the detectors were analyzed. Mean testicular doses from the intensity-modulated radiotherapy and volumetric-modulated arc radiotherapy per fraction calculated in the treatment planning system were 16.3 ± 10.3 cGy vs 21.5 ± 11.2 cGy (p = 0.03) at 6 MV, 13.4 ± 10.4 cGy vs 17.8 ± 10.7 cGy (p = 0.04) at 10 MV, and 10.6 ± 8.5 cGy vs 14.5 ± 8.6 cGy (p = 0.03) at 15 MV, respectively. Mean scattered testicular doses in the phantom measurements were 99.5 ± 17.2 cGy, 118.7 ± 16.4 cGy, and 193.9 ± 14.5 cGy at 6, 10, and 15 MV, respectively, in the intensity-modulated radiotherapy plans. In the volumetric-modulated arc radiotherapy plans, corresponding testicular doses per course were 90.4 ± 16.3 cGy, 103.6 ± 16.4 cGy, and 139.3 ± 14.6 cGy at 6, 10, and 15 MV, respectively. In conclusions, this study was the first to measure the incidental testicular doses by intensity-modulated radiotherapy and volumetric-modulated arc radiotherapy plans at different energy levels during prostate-only irradiation. Higher photon energy and volumetric-modulated arc radiotherapy plans resulted in higher incidental testicular doses compared with lower photon energy and intensity-modulated radiotherapy plans.

  7. Level-one modules library for DSNP: Dynamic Simulator for Nuclear Power-plants

    International Nuclear Information System (INIS)

    Saphier, D.

    1978-09-01

    The Dynamic Simulator for Nuclear Power-plants (DSNP) is a system of programs and data sets by which a nuclear power plant or part thereof can be simulated at different levels of sophistication. The acronym DSNP is used interchangeably for the DSNP language, for the DSNP precompiler, for the DSNP libraries, and for the DSNP document generator. The DSNP language is a set of simple block oriented statements, which together with the appropriate data, comprise a simulation of a nuclear power plant. The majority of the DSNP statements will result in the inclusion of a simulated physical module into the program. FORTRAN statements can be inserted with no restrictions among DSNP statements

  8. Extended Pulse-Powered Humidity-Freeze Cycling for Testing Module-Level Power Electronics

    Energy Technology Data Exchange (ETDEWEB)

    Hacke, Peter L [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Rodriguez, Miguel [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Kempe, Michael D [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Repins, Ingrid L [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-11-28

    An EMI suppression capacitor (polypropylene film type) failed by 'popcorning' due to vapor outgassing in pulse powered humidity-freeze cycles. No shorts or shunts could be detected despite mildly corroded metallization visible in the failed capacitor. Humidity-freeze cycling is optimized to break into moisture barriers. However, further studies will be required on additional module level power electronic (MLPE) devices to optimize the stress testing for condensation to precipitate any weakness to short circuiting and other humidity/bias failure modes.

  9. Discovery of novel isoforms of huntingtin reveals a new hominid-specific exon.

    Directory of Open Access Journals (Sweden)

    Albert Ruzo

    Full Text Available Huntington's disease (HD is a devastating neurological disorder that is caused by an expansion of the poly-Q tract in exon 1 of the Huntingtin gene (HTT. HTT is an evolutionarily conserved and ubiquitously expressed protein that has been linked to a variety of functions including transcriptional regulation, mitochondrial function, and vesicle transport. This large protein has numerous caspase and calpain cleavage sites and can be decorated with several post-translational modifications such as phosphorylations, acetylations, sumoylations, and palmitoylations. However, the exact function of HTT and the role played by its modifications in the cell are still not well understood. Scrutiny of HTT function has been focused on a single, full length mRNA. In this study, we report the discovery of 5 novel HTT mRNA splice isoforms that are expressed in normal and HTT-expanded human embryonic stem cell (hESC lines as well as in cortical neurons differentiated from hESCs. Interestingly, none of the novel isoforms generates a truncated protein. Instead, 4 of the 5 new isoforms specifically eliminate domains and modifications to generate smaller HTT proteins. The fifth novel isoform incorporates a previously unreported additional exon, dubbed 41b, which is hominid-specific and introduces a potential phosphorylation site in the protein. The discovery of this hominid-specific isoform may shed light on human-specific pathogenic mechanisms of HTT, which could not be investigated with current mouse models of the disease.

  10. Discovery of Novel Isoforms of Huntingtin Reveals a New Hominid-Specific Exon

    Science.gov (United States)

    Popowski, Melissa; Haremaki, Tomomi; Croft, Gist F.; Deglincerti, Alessia; Brivanlou, Ali H.

    2015-01-01

    Huntington’s disease (HD) is a devastating neurological disorder that is caused by an expansion of the poly-Q tract in exon 1 of the Huntingtin gene (HTT). HTT is an evolutionarily conserved and ubiquitously expressed protein that has been linked to a variety of functions including transcriptional regulation, mitochondrial function, and vesicle transport. This large protein has numerous caspase and calpain cleavage sites and can be decorated with several post-translational modifications such as phosphorylations, acetylations, sumoylations, and palmitoylations. However, the exact function of HTT and the role played by its modifications in the cell are still not well understood. Scrutiny of HTT function has been focused on a single, full length mRNA. In this study, we report the discovery of 5 novel HTT mRNA splice isoforms that are expressed in normal and HTT-expanded human embryonic stem cell (hESC) lines as well as in cortical neurons differentiated from hESCs. Interestingly, none of the novel isoforms generates a truncated protein. Instead, 4 of the 5 new isoforms specifically eliminate domains and modifications to generate smaller HTT proteins. The fifth novel isoform incorporates a previously unreported additional exon, dubbed 41b, which is hominid-specific and introduces a potential phosphorylation site in the protein. The discovery of this hominid-specific isoform may shed light on human-specific pathogenic mechanisms of HTT, which could not be investigated with current mouse models of the disease. PMID:26010866

  11. Loss of Huntingtin stimulates capture of retrograde dense-core vesicles to increase synaptic neuropeptide stores.

    Science.gov (United States)

    Bulgari, Dinara; Deitcher, David L; Levitan, Edwin S

    2017-08-01

    The Huntington's disease protein Huntingtin (Htt) regulates axonal transport of dense-core vesicles (DCVs) containing neurotrophins and neuropeptides. DCVs travel down axons to reach nerve terminals where they are either captured in synaptic boutons to support later release or reverse direction to reenter the axon as part of vesicle circulation. Currently, the impact of Htt on DCV dynamics in the terminal is unknown. Here we report that knockout of Drosophila Htt selectively reduces retrograde DCV flux at proximal boutons of motoneuron terminals. However, initiation of retrograde transport at the most distal bouton and transport velocity are unaffected suggesting that synaptic capture rate of these retrograde DCVs could be altered. In fact, tracking DCVs shows that retrograde synaptic capture efficiency is significantly elevated by Htt knockout or knockdown. Furthermore, synaptic boutons contain more neuropeptide in Htt knockout larvae even though bouton size, single DCV fluorescence intensity, neuropeptide release in response to electrical stimulation and subsequent activity-dependent capture are unaffected. Thus, loss of Htt increases synaptic capture as DCVs travel by retrograde transport through boutons resulting in reduced transport toward the axon and increased neuropeptide in the terminal. These results therefore identify native Htt as a regulator of synaptic capture and neuropeptide storage. Copyright © 2017 Elsevier GmbH. All rights reserved.

  12. Sequestration of Sup35 by aggregates of huntingtin fragments causes toxicity of [PSI+] yeast.

    Science.gov (United States)

    Zhao, Xiaohong; Park, Yang-Nim; Todor, Horia; Moomau, Christine; Masison, Daniel; Eisenberg, Evan; Greene, Lois E

    2012-07-06

    Expression of huntingtin fragments with 103 glutamines (HttQ103) is toxic in yeast containing either the [PIN(+)] prion, which is the amyloid form of Rnq1, or [PSI(+)] prion, which is the amyloid form of Sup35. We find that HttQP103, which has a polyproline region at the C-terminal end of the polyQ repeat region, is significantly more toxic in [PSI(+)] yeast than in [PIN(+)], even though HttQP103 formed multiple aggregates in both [PSI(+)] and [PIN(+)] yeast. This toxicity was only observed in the strong [PSI(+)] variant, not the weak [PSI(+)] variant, which has more soluble Sup35 present than the strong variant. Furthermore, expression of the MC domains of Sup35, which retains the C-terminal domain of Sup35, but lacks the N-terminal prion domain, almost completely rescued HttQP103 toxicity, but was less effective in rescuing HttQ103 toxicity. Therefore, the toxicity of HttQP103 in yeast containing the [PSI(+)] prion is primarily due to sequestration of the essential protein, Sup35.

  13. Length and sequence dependence in the association of Huntingtin protein with lipid membranes

    Science.gov (United States)

    Jawahery, Sudi; Nagarajan, Anu; Matysiak, Silvina

    2013-03-01

    There is a fundamental gap in our understanding of how aggregates of mutant Huntingtin protein (htt) with overextended polyglutamine (polyQ) sequences gain the toxic properties that cause Huntington's disease (HD). Experimental studies have shown that the most important step associated with toxicity is the binding of mutant htt aggregates to lipid membranes. Studies have also shown that flanking amino acid sequences around the polyQ sequence directly affect interactions with the lipid bilayer, and that polyQ sequences of greater than 35 glutamine repeats in htt are a characteristic of HD. The key steps that determine how flanking sequences and polyQ length affect the structure of lipid bilayers remain unknown. In this study, we use atomistic molecular dynamics simulations to study the interactions between lipid membranes of varying compositions and polyQ peptides of varying lengths and flanking sequences. We find that overextended polyQ interactions do cause deformation in model membranes, and that the flanking sequences do play a role in intensifying this deformation by altering the shape of the affected regions.

  14. Huntingtin coordinates the dynein-mediated dynamic positioning of endosomes and lysosomes

    Science.gov (United States)

    Caviston, Juliane P.; Zajac, Allison L.; Tokito, Mariko; Holzbaur, Erika L.F.

    2011-01-01

    Huntingtin (Htt) is a membrane-associated scaffolding protein that interacts with microtubule motors as well as actin-associated adaptor molecules. We examined a role for Htt in the dynein-mediated intracellular trafficking of endosomes and lysosomes. In HeLa cells depleted of either Htt or dynein, early, recycling, and late endosomes (LE)/lysosomes all become dispersed. Despite altered organelle localization, kinetic assays indicate only minor defects in intracellular trafficking. Expression of full-length Htt is required to restore organelle localization in Htt-depleted cells, supporting a role for Htt as a scaffold that promotes functional interactions along its length. In dynein-depleted cells, LE/lysosomes accumulate in tight patches near the cortex, apparently enmeshed by cortactin-positive actin filaments; Latrunculin B-treatment disperses these patches. Peripheral LE/lysosomes in dynein-depleted cells no longer colocalize with microtubules. Htt may be required for this off-loading, as the loss of microtubule association is not seen in Htt-depleted cells or in cells depleted of both dynein and Htt. Inhibition of kinesin-1 relocalizes peripheral LE/lysosomes induced by Htt depletion but not by dynein depletion, consistent with their detachment from microtubules upon dynein knockdown. Together, these data support a model of Htt as a facilitator of dynein-mediated trafficking that may regulate the cytoskeletal association of dynamic organelles. PMID:21169558

  15. A new Caenorhabditis elegans model of human huntingtin 513 aggregation and toxicity in body wall muscles.

    Directory of Open Access Journals (Sweden)

    Amy L Lee

    Full Text Available Expanded polyglutamine repeats in different proteins are the known determinants of at least nine progressive neurodegenerative disorders whose symptoms include cognitive and motor impairment that worsen as patients age. One such disorder is Huntington's Disease (HD that is caused by a polyglutamine expansion in the human huntingtin protein (htt. The polyglutamine expansion destabilizes htt leading to protein misfolding, which in turn triggers neurodegeneration and the disruption of energy metabolism in muscle cells. However, the molecular mechanisms that underlie htt proteotoxicity have been somewhat elusive, and the muscle phenotypes have not been well studied. To generate tools to elucidate the basis for muscle dysfunction, we engineered Caenorhabditis elegans to express a disease-associated 513 amino acid fragment of human htt in body wall muscle cells. We show that this htt fragment aggregates in C. elegans in a polyglutamine length-dependent manner and is toxic. Toxicity manifests as motor impairment and a shortened lifespan. Compared to previous models, the data suggest that the protein context in which a polyglutamine tract is embedded alters aggregation propensity and toxicity, likely by affecting interactions with the muscle cell environment.

  16. Comparative Study of Modulation Techniques for Two-Level Voltage Source Inverters

    Directory of Open Access Journals (Sweden)

    Barry W. Williams

    2016-06-01

    Full Text Available A detailed comparative study of modulation techniques for single and three phase dc-ac inverters is presented.  Sinusoidal Pulse Width Modulation, Triplen Sinusoidal Pulse Width Modulation, Space Vector Modulation, Selective Harmonic Elimination and Wavelet Modulation are assessed and compared in terms of maximum fundamental output, harmonic performance, switching losses and operational mode.  The presented modulation techniques are applied to single and three phase voltage source inverters and are simulated using SIMULINK.  The simulation results clarify the inverter performance achieved using the different modulations techniques.

  17. Intracellular calcium levels determine differential modulation of allosteric interactions within G protein-coupled receptor heteromers.

    Science.gov (United States)

    Navarro, Gemma; Aguinaga, David; Moreno, Estefania; Hradsky, Johannes; Reddy, Pasham P; Cortés, Antoni; Mallol, Josefa; Casadó, Vicent; Mikhaylova, Marina; Kreutz, Michael R; Lluís, Carme; Canela, Enric I; McCormick, Peter J; Ferré, Sergi

    2014-11-20

    The pharmacological significance of the adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromer is well established and it is being considered as an important target for the treatment of Parkinson’s disease and other neuropsychiatric disorders. However, the physiological factors that control its distinctive biochemical properties are still unknown. We demonstrate that different intracellular Ca2+ levels exert a differential modulation of A2AR-D2R heteromer-mediated adenylyl-cyclase and MAPK signaling in striatal cells. This depends on the ability of low and high Ca2+ levels to promote a selective interaction of the heteromer with the neuronal Ca2+-binding proteins NCS-1 and calneuron-1, respectively. These Ca2+-binding proteins differentially modulate allosteric interactions within the A2AR-D2R heteromer, which constitutes a unique cellular device that integrates extracellular (adenosine and dopamine) and intracellular (Ca+2) signals to produce a specific functional response.

  18. Lithium modulates the chronic stress-induced effect on blood glucose level of male rats

    Directory of Open Access Journals (Sweden)

    Popović Nataša

    2010-01-01

    Full Text Available In the present study we examined gross changes in the mass of whole adrenal glands and that of the adrenal cortex, as well as the serum corticosterone and glucose level of mature male Wistar rats subjected to three different treatments: animals subjected to chronic restraint-stress, animals injected with lithium (Li and chronically stressed rats treated with Li. Under all three conditions we observed hypertrophy of whole adrenals, as well as the adrenal cortices. Chronic restraint stress, solely or in combination with Li treatment, significantly elevated the corticosterone level, but did not change the blood glucose level. Animals treated only with Li exhibited an elevated serum corticosterone level and blood glucose level. The aim of our study was to investigate the modulation of the chronic stress-induced effect on the blood glucose level by lithium, as a possible mechanism of avoiding the damage caused by chronic stress. Our results showed that lithium is an agent of choice which may help to reduce stress-elevated corticosterone and replenish exhausted glucose storages in an organism.

  19. Experiments of Multi-Level Read-Only Recording Using Readout Signal Wave-Shape Modulation

    International Nuclear Information System (INIS)

    Yi, Tang; Jing, Pei; Long-Fa, Pan; Yi, Ni; Hua, Hu; Bu-Qing, Zhang

    2008-01-01

    An innovative multilevel read-only recording method is proposed. In this method, a short pit/land is deliberately inserted to the original land/pit. This modifies the wave-shape of readout signal. Taking the wave-shape as the symbol of level detection, a signal wave-shape modulation (SWSM) multilevel method is realized. This method is carried out and validated on the DVD read-only manufacture and readout system. A capacity of 15 GB can be expected, and a bit error rate of 10 −4 is achieved. The capacity can meet the demand of high definition movie publication. This method also provides a potential multi-level solution for other storage formats and systems. (fundamental areas of phenomenology (including applications))

  20. Adipose tissue branched chain amino acid (BCAA) metabolism modulates circulating BCAA levels.

    Science.gov (United States)

    Herman, Mark A; She, Pengxiang; Peroni, Odile D; Lynch, Christopher J; Kahn, Barbara B

    2010-04-09

    Whereas the role of adipose tissue in glucose and lipid homeostasis is widely recognized, its role in systemic protein and amino acid metabolism is less well-appreciated. In vitro and ex vivo experiments suggest that adipose tissue can metabolize substantial amounts of branched chain amino acids (BCAAs). However, the role of adipose tissue in regulating BCAA metabolism in vivo is controversial. Interest in the contribution of adipose tissue to BCAA metabolism has been renewed with recent observations demonstrating down-regulation of BCAA oxidation enzymes in adipose tissue in obese and insulin-resistant humans. Using gene set enrichment analysis, we observe alterations in adipose-tissue BCAA enzyme expression caused by adipose-selective genetic alterations in the GLUT4 glucose-transporter expression. We show that the rate of adipose tissue BCAA oxidation per mg of tissue from normal mice is higher than in skeletal muscle. In mice overexpressing GLUT4 specifically in adipose tissue, we observe coordinate down-regulation of BCAA metabolizing enzymes selectively in adipose tissue. This decreases BCAA oxidation rates in adipose tissue, but not in muscle, in association with increased circulating BCAA levels. To confirm the capacity of adipose tissue to modulate circulating BCAA levels in vivo, we demonstrate that transplantation of normal adipose tissue into mice that are globally defective in peripheral BCAA metabolism reduces circulating BCAA levels by 30% (fasting)-50% (fed state). These results demonstrate for the first time the capacity of adipose tissue to catabolize circulating BCAAs in vivo and that coordinate regulation of adipose-tissue BCAA enzymes may modulate circulating BCAA levels.

  1. Power penalties for multi-level PAM modulation formats at arbitrary bit error rates

    Science.gov (United States)

    Kaliteevskiy, Nikolay A.; Wood, William A.; Downie, John D.; Hurley, Jason; Sterlingov, Petr

    2016-03-01

    There is considerable interest in combining multi-level pulsed amplitude modulation formats (PAM-L) and forward error correction (FEC) in next-generation, short-range optical communications links for increased capacity. In this paper we derive new formulas for the optical power penalties due to modulation format complexity relative to PAM-2 and due to inter-symbol interference (ISI). We show that these penalties depend on the required system bit-error rate (BER) and that the conventional formulas overestimate link penalties. Our corrections to the standard formulas are very small at conventional BER levels (typically 1×10-12) but become significant at the higher BER levels enabled by FEC technology, especially for signal distortions due to ISI. The standard formula for format complexity, P = 10log(L-1), is shown to overestimate the actual penalty for PAM-4 and PAM-8 by approximately 0.1 and 0.25 dB respectively at 1×10-3 BER. Then we extend the well-known PAM-2 ISI penalty estimation formula from the IEEE 802.3 standard 10G link modeling spreadsheet to the large BER case and generalize it for arbitrary PAM-L formats. To demonstrate and verify the BER dependence of the ISI penalty, a set of PAM-2 experiments and Monte-Carlo modeling simulations are reported. The experimental results and simulations confirm that the conventional formulas can significantly overestimate ISI penalties at relatively high BER levels. In the experiments, overestimates up to 2 dB are observed at 1×10-3 BER.

  2. The role of the habenula-interpeduncular pathway in modulating levels of circulating adrenal hormones.

    Science.gov (United States)

    Murray, M; Murphy, C A; Ross, L L; Haun, F

    1994-01-01

    The fasciculus retroflexus (FR) is the major pathway by which the medial and lateral habenular nuclei project to the interpeduncular nucleus (IPN) and ventral tegmentum. Recent work has suggested that the habenula-interpeduncular system may be involved in the regulation of states of arousal. Bilateral FR lesions have been shown to disrupt chronically, and habenula transplants have been shown to restore normal sleep patterns in rats [J. NeuroscL, 12 (1992) 3282-3290]. In this study, we examined whether FR lesions and habenula cell transplants would also modify chronically the circulating plasma levels of the stress-related hormones, norepinephrine (NE), epinephrine (EPI) and corticosterone. When plasma samples were obtained via retro-orbital eye-bleed during anesthesia, animals with FR lesions had significantly increased levels of plasma NE, EPI and corticosterone 2-3 months postoperatively compared to unoperated controls. Transplants of embryonic habenula cells placed near the denervated IPN in FR-lesioned animals restored levels of NE and EPI to normal, but did not attenuate elevated corticosterone levels. When plasma samples were obtained in conscious animals via indwelling arterial cannulae, FR-lesioned rats likewise exhibited increased basal levels of corticosterone but plasma levels of catecholamines were similar to those of unoperated controls. Differences in our results obtained using the two methods of blood sampling may be explained by the effects of anesthesia and stress associated with the eye-bleed method. Thus, the effect of FR lesions in increasing plasma levels of catecholamines may not reflect a difference in basal hormone levels, but a heightened sympathetic adrenomedullary response to stress. While these results indicate that the integrity of the habenular efferent pathway is important in modulating circulating levels of hormones associated with the stress response, two separate mechanisms appear to control its interactions with sympathetic

  3. Parvovirus B19 infection modulates the levels of cytokines in the plasma of rheumatoid arthritis patients.

    Science.gov (United States)

    Naciute, Milda; Mieliauskaite, Diana; Rugiene, Rita; Maciunaite, Gabriele; Mauricas, Mykolas; Murovska, Modra; Girkontaite, Irute

    2017-08-01

    Parvovirus B19 (B19V) infection is associated with various autoimmune diseases. We investigated the levels of pro-inflammatory (IFNᵧ, TNFα, IL-2, IL-12) and anti-inflammatory (IL-4, IL-10) cytokines in the plasma of B19V DNA positive (B19 + ) and negative (B19 - ) rheumatoid arthritis (RA) patients in comparison with the control group (healthy persons). Blood samples were collected from 118 patients with RA and 49 healthy voluntaries. B19V sequence was determined in whole blood and cell-free plasma DNA by nested PCR. The levels of cytokines in the plasma and cell culture medium from Concanavalin A (ConA) or B19V VP1 protein stimulated PBMC were determined by ELISA. The levels of IL-4, IL-10, IL-12, IL-2 and TNFα were higher in plasma of RA patients in comparison with control persons. B19 + controls and RA patients had lower levels of IFNᵧ in comparison with B19 - controls and RA patients. Within RA patients the plasma levels of IFNᵧ were lower in patients with low RA disease activity or remission. Plasma level of IL-4 was increased and IL-10 level was decreased in B19 + RA patients in comparison with B19 - RA patients and did not differ between B19 + and B19 - controls. B19V infection did not affect plasma levels of IL-12, IL-2, and TNFα. ConA and B19 VP1 protein stimulated PBMC from RA patients produced less IFNᵧ than stimulated PBMC from the healthy controls. B19V infection could differently modulate the amount of cytokines in the plasma of healthy persons and RA patients. Decreased production of IFNᵧ and raised level of plasma IL-4 in RA patients could lower antiviral clearance. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. ∑∆ Modulator System-Level Considerations for Hearing-Aid Audio Class-D Output Stage Application

    DEFF Research Database (Denmark)

    Pracný, Peter; Bruun, Erik

    2012-01-01

    This paper deals with a system-level design of a digital sigma-delta (∑∆) modulator for hearing-aid audio Class D output stage application. The aim of this paper is to provide a thorough discussion on various possibilities and tradeoffs of ∑∆ modulator system-level design parameter combinations...... - order, oversampling ratio (OSR) and number of bits in the quantizer - including their impact on interpolation filter design as well. The system is kept in digital domain up to the input of the Class D power stage including the digital pulse width modulation (DPWM) block. Notes on the impact of the DPWM...

  5. The Wnt receptor Ryk reduces neuronal and cell survival capacity by repressing FOXO activity during the early phases of mutant huntingtin pathogenicity.

    Directory of Open Access Journals (Sweden)

    Cendrine Tourette

    2014-06-01

    Full Text Available The Wnt receptor Ryk is an evolutionary-conserved protein important during neuronal differentiation through several mechanisms, including γ-secretase cleavage and nuclear translocation of its intracellular domain (Ryk-ICD. Although the Wnt pathway may be neuroprotective, the role of Ryk in neurodegenerative disease remains unknown. We found that Ryk is up-regulated in neurons expressing mutant huntingtin (HTT in several models of Huntington's disease (HD. Further investigation in Caenorhabditis elegans and mouse striatal cell models of HD provided a model in which the early-stage increase of Ryk promotes neuronal dysfunction by repressing the neuroprotective activity of the longevity-promoting factor FOXO through a noncanonical mechanism that implicates the Ryk-ICD fragment and its binding to the FOXO co-factor β-catenin. The Ryk-ICD fragment suppressed neuroprotection by lin-18/Ryk loss-of-function in expanded-polyQ nematodes, repressed FOXO transcriptional activity, and abolished β-catenin protection of mutant htt striatal cells against cell death vulnerability. Additionally, Ryk-ICD was increased in the nucleus of mutant htt cells, and reducing γ-secretase PS1 levels compensated for the cytotoxicity of full-length Ryk in these cells. These findings reveal that the Ryk-ICD pathway may impair FOXO protective activity in mutant polyglutamine neurons, suggesting that neurons are unable to efficiently maintain function and resist disease from the earliest phases of the pathogenic process in HD.

  6. Enhanced susceptibility to seizures modulated by high interleukin-1β levels during early life malnutrition.

    Science.gov (United States)

    Simão, Fabrício; Habekost Oliveira, Victória; Lahorgue Nunes, Magda

    2016-10-01

    Early malnutrition in life has permanent consequences on brain development and has been suggested to influence seizure susceptibility. Despite malnutrition is not a direct cause of seizures, we hypothesize that malnutrition may modulate inflammatory response and result in cerebral vulnerability to seizures. In this study, we provide evidence that malnutrition may increase susceptibility to seizures in the postnatal period by interleukin-1β (IL-1β) in the hippocampus. Malnourished rats were maintained on a nutritional deprivation regimen from postnatal day 1 (P1) to P10. From P7 to P10, the threshold to seizures induced by flurothyl was used as an index of seizure susceptibility. ELISA and western blot was performed to evaluate levels of IL-1β, IL-1R1, PSD-95 and synapsin. The role of inflammation in the changes of seizure threshold was studied with inhibitors of IL-1β and IL-1R1. A significant decrease in body weight and seizure threshold was observed in postnatal malnourished rats. Early malnutrition modulates inflammation by high levels of IL-1β in hippocampus and in serum. Furthermore, our malnutrition paradigm induced an increase in corticosterone levels. Injection of IL-1β and IL-1R1 inhibitors before seizure induction augments seizure threshold in malnourished rats similar to nourished group. Malnutrition did not change PSD-95 and synapsin expression in the hippocampus. We suggest that malnutrition-induced inflammation might contribute to seizure susceptibility in the postnatal period. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1150-1159, 2016. © 2016 Wiley Periodicals, Inc.

  7. Resveratrol confers protection against rotenone-induced neurotoxicity by modulating myeloperoxidase levels in glial cells.

    Directory of Open Access Journals (Sweden)

    Chi Young Chang

    Full Text Available Myeloperoxidase (MPO functions as a key molecular component of the host defense system against diverse pathogens. We have previously reported that increased MPO levels and activity is a distinguishing feature of rotenone-exposed glial cells, and that either overactivation or deficiency of MPO leads to pathological conditions in the brain. Here, we provide that modulation of MPO levels in glia by resveratrol confers protective effects on rotenone-induced neurotoxicity. We show that resveratrol significantly reduced MPO levels but did not trigger abnormal nitric oxide (NO production in microglia and astrocytes. Resveratrol-induced down-regulation of MPO, in the absence of an associated overproduction of NO, markedly attenuated rotenone-triggered inflammatory responses including phagocytic activity and reactive oxygen species production in primary microglia and astrocytes. In addition, impaired responses of primary mixed glia from Mpo (-/- mice to rotenone were relieved by treatment with resveratrol. We further show that rotenone-induced neuronal injury, particularly dopaminergic cell death, was attenuated by resveratrol in neuron-glia co-cultures, but not in neurons cultured alone. Similar regulatory effects of resveratrol on MPO levels were observed in microglia treated with MPP(+, another Parkinson's disease-linked neurotoxin, supporting the beneficial effects of resveratrol on the brain. Collectively, our findings provide that resveratrol influences glial responses to rotenone by regulating both MPO and NO, and thus protects against rotenone-induced neuronal injury.

  8. Open-Source Python Modules to Estimate Level Ice Thickness from Ice Charts

    Science.gov (United States)

    Geiger, C. A.; Deliberty, T. L.; Bernstein, E. R.; Helfrich, S.

    2012-12-01

    A collaborative research effort between the University of Delaware (UD) and National Ice Center (NIC) addresses the task of providing open-source translations of sea ice stage-of-development into level ice thickness estimates on a 4km grid for the Interactive Multisensor Snow and Ice Mapping System (IMS). The characteristics for stage-of-development are quantified from remote sensing imagery with estimates of level ice thickness categories originating from World Meteorological Organization (WMO) egg coded ice charts codified since the 1970s. Conversions utilize Python scripting modules which transform electronic ice charts with WMO egg code characteristics into five level ice thickness categories, in centimeters, (0-10, 10-30, 30-70, 70-120, >120cm) and five ice types (open water, first year pack ice, fast ice, multiyear ice, and glacial ice with a reserve slot for deformed ice fractions). Both level ice thickness categories and ice concentration fractions are reported with uncertainties propagated based on WMO ice stage ranges which serve as proxy estimates for standard deviation. These products are in preparation for use by NCEP, CMC, and NAVO by 2014 based on their modeling requirements for daily products in near-real time. In addition to development, continuing research tests the value of these estimated products against in situ observations to improve both value and uncertainty estimates.

  9. Three-Level Inverters with Common-Mode Voltage Cancellation Based on Synchronous Pulsewidth Modulation

    DEFF Research Database (Denmark)

    Oleschuk, Valentin; Blaabjerg, Frede

    2002-01-01

    A novel method of direct synchronous pulse-width modulation (PWM) is disseminated to three-level voltage source inverters with control algorithms with elimination of the common-mode voltages in three-phase drive systems with PWM. It provides smooth pulses-ratio changing and a quarter-wave symmetry...... of the voltage waveforms during the whole control range including overmodulation. Continuous, discontinuous and "direct-direct" schemes of synchronous PWM with both algebraic and trigonometric control functions have been analysed and compared. Simulations give the behaviour of the proposed methods and show some...... advantages of synchronous PWM in comparison with asynchronous at low ratios between the switching frequency and fundamental frequency....

  10. Two-level modulation scheme to reduce latency for optical mobile fronthaul networks.

    Science.gov (United States)

    Sung, Jiun-Yu; Chow, Chi-Wai; Yeh, Chien-Hung; Chang, Gee-Kung

    2016-10-31

    A system using optical two-level orthogonal-frequency-division-multiplexing (OFDM) - amplitude-shift-keying (ASK) modulation is proposed and demonstrated to reduce the processing latency for the optical mobile fronthaul networks. At the proposed remote-radio-head (RRH), the high data rate OFDM signal does not need to be processed, but is directly launched into a high speed photodiode (HSPD) and subsequently emitted by an antenna. Only a low bandwidth PD is needed to recover the low data rate ASK control signal. Hence, it is simple and provides low-latency. Furthermore, transporting the proposed system over the already deployed optical-distribution-networks (ODNs) of passive-optical-networks (PONs) is also demonstrated with 256 ODN split-ratios.

  11. The importance of macro- versus microstructure in modulating light levels inside coral colonies

    DEFF Research Database (Denmark)

    Kaniewska, Paulina; Magnusson, Sveinn H.; Anthony, Ken R. N.

    2011-01-01

    Adjusting the light exposure and capture of their symbiotic photosynthetic dinoflagellates (genus Symbiodinium Freud.) is central to the success of reef-building corals (order Scleractinia) across high spatio-temporal variation in the light environment of coral reefs. We tested the hypothesis...... irradiances at the level of coral photosymbionts. Key index words: irradiance; morphology; photoacclimation; scale; scleractinian coral; Symbiodinium Abbreviations: a chl a, specific absorption coefficient of chl a; Ddn, diadinoxanthin; Dtn, diatoxanthin; GBR, Great Barrier Reef; GFP, green fluorescent...... that optical properties of tissues in some coral species can provide light management at the tissue scale comparable to light modulation by colony architecture in other species. We compared within-tissue scalar irradiance in two coral species from the same light habitat but with contrasting colony growth forms...

  12. Synchronised Voltage Space Vector Modulation for Three-level Inverters with Common-mode Voltage Elimination

    DEFF Research Database (Denmark)

    Oleschuk, Valentin; Blaabjerg, Frede

    2002-01-01

    A novel method of direct synchronous pulse-width modulation (PWM) is disseminated to three-level voltage source inverters with control algorithms with elimination of the common-mode voltages in three-phase drive systems with PWM. It provides smooth pulses-ratio changing and a quarter-wave symmetry...... of the voltage waveforms during the whole control range including overmodulation. Continuous, discontinuous and "direct-direct" schemes of synchronous PWM with both algebraic and trigonometric control functions have been analysed and compared. Simulations give the behaviour of the proposed methods and show some...... advantages of synchronous PWM in comparison with asynchronous at low ratios between the switching frequency and fundamental frequency....

  13. Module-level DC/DC conversion for photovotaic systems : the delta-conversion concept

    NARCIS (Netherlands)

    Bergveld, H.J.; Büthker, D.; Castello, C.; Doorn, T.S.; Jong, de A.; van Otten, R.; Waal, de K.

    2013-01-01

    Photovoltaic (PV) systems are increasingly used to generate electrical energy from solar irradiation incident on PV modules. PV modules are formed by placing many PV cells in series. The PV system is then formed by placing a number of PV modules in series in a string. In practical cases, differences

  14. Binding, internalization and fate of Huntingtin Exon1 fibrillar assemblies in mitotic and nonmitotic neuroblastoma cells.

    Science.gov (United States)

    Ruiz-Arlandis, G; Pieri, L; Bousset, L; Melki, R

    2016-02-01

    The aggregation of Huntingtin (HTT) protein and of its moiety encoded by its Exon1 (HTTExon1) into fibrillar structures inside neurons is the molecular hallmark of Huntington's disease. Prion-like transmission of these aggregates between cells has been demonstrated. The cell-to-cell transmission mechanisms of these protein aggregates and the susceptibility of different kinds of neuronal cells to these toxic assemblies still need assessment. Here, we documented the binding to and internalization by differentiated and undifferentiated neuroblastoma cells of exogenous fibrillar HTTExon1 and polyglutamine (polyQ) polypeptides containing the same number of glutamines. We assessed the contribution of endocytosis to fibrillar HTTExon1 uptake, their intracellular localization and fate. We observed that undifferentiated neuroblastoma cells were more susceptible to fibrillar HTTExon1 and polyQ than their differentiated counterparts. Furthermore, we demonstrated that exogenous HTTExon1 aggregates are mainly taken up by endocytosis and directed to lysosomal compartments in both mitotic and quiescent cells. These data suggest that the rates of endocytic processes that differ in mitotic and quiescent cells strongly impact the uptake of exogenous HTTExon1 and polyQ fibrils. This may be either the consequence of distinct metabolisms or distributions of specific protein partners for amyloid-like assemblies at the surface of highly dividing versus quiescent cells. Our results highlight the importance of endocytic processes in the internalization of exogenous HTTExon1 fibrils and suggest that a proportion of those assemblies reach the cytosol where they can amplify by recruiting the endogenous protein after escaping, by yet an unknown process, from the endo-lysosomal compartments. © 2015 British Neuropathological Society.

  15. Scalable production in human cells and biochemical characterization of full-length normal and mutant huntingtin.

    Directory of Open Access Journals (Sweden)

    Bin Huang

    Full Text Available Huntingtin (Htt is a 350 kD intracellular protein, ubiquitously expressed and mainly localized in the cytoplasm. Huntington's disease (HD is caused by a CAG triplet amplification in exon 1 of the corresponding gene resulting in a polyglutamine (polyQ expansion at the N-terminus of Htt. Production of full-length Htt has been difficult in the past and so far a scalable system or process has not been established for recombinant production of Htt in human cells. The ability to produce Htt in milligram quantities would be a prerequisite for many biochemical and biophysical studies aiming in a better understanding of Htt function under physiological conditions and in case of mutation and disease. For scalable production of full-length normal (17Q and mutant (46Q and 128Q Htt we have established two different systems, the first based on doxycycline-inducible Htt expression in stable cell lines, the second on "gutless" adenovirus mediated gene transfer. Purified material has then been used for biochemical characterization of full-length Htt. Posttranslational modifications (PTMs were determined and several new phosphorylation sites were identified. Nearly all PTMs in full-length Htt localized to areas outside of predicted alpha-solenoid protein regions. In all detected N-terminal peptides methionine as the first amino acid was missing and the second, alanine, was found to be acetylated. Differences in secondary structure between normal and mutant Htt, a helix-rich protein, were not observed in our study. Purified Htt tends to form dimers and higher order oligomers, thus resembling the situation observed with N-terminal fragments, although the mechanism of oligomer formation may be different.

  16. Trace levels of innate immune response modulating impurities (IIRMIs) synergize to break tolerance to therapeutic proteins.

    Science.gov (United States)

    Verthelyi, Daniela; Wang, Vivian

    2010-12-22

    Therapeutic proteins such as monoclonal antibodies, replacement enzymes and toxins have significantly improved the therapeutic options for multiple diseases, including cancer and inflammatory diseases as well as enzyme deficiencies and inborn errors of metabolism. However, immune responses to these products are frequent and can seriously impact their safety and efficacy. Of the many factors that can impact protein immunogenicity, this study focuses on the role of innate immune response modulating impurities (IIRMIs) that could be present despite product purification and whether these impurities can synergize to facilitate an immunogenic response to therapeutic proteins. Using lipopolysaccharide (LPS) and CpG ODN as IIRMIs we showed that trace levels of these impurities synergized to induce IgM, IFNγ, TNFα and IL-6 expression. In vivo, trace levels of these impurities synergized to increase antigen-specific IgG antibodies to ovalbumin. Further, whereas mice treated with human erythropoietin showed a transient increase in hematocrit, those that received human erythropoietin containing low levels of IIRMIs had reduced response to erythropoietin after the 1(st) dose and developed long-lasting anemia following subsequent doses. This suggests that the presence of IIRMIs facilitated a breach in tolerance to the endogenous mouse erythropoietin. Overall, these studies indicate that the risk of enhancing immunogenicity should be considered when establishing acceptance limits of IIRMIs for therapeutic proteins.

  17. Trace levels of innate immune response modulating impurities (IIRMIs synergize to break tolerance to therapeutic proteins.

    Directory of Open Access Journals (Sweden)

    Daniela Verthelyi

    Full Text Available Therapeutic proteins such as monoclonal antibodies, replacement enzymes and toxins have significantly improved the therapeutic options for multiple diseases, including cancer and inflammatory diseases as well as enzyme deficiencies and inborn errors of metabolism. However, immune responses to these products are frequent and can seriously impact their safety and efficacy. Of the many factors that can impact protein immunogenicity, this study focuses on the role of innate immune response modulating impurities (IIRMIs that could be present despite product purification and whether these impurities can synergize to facilitate an immunogenic response to therapeutic proteins. Using lipopolysaccharide (LPS and CpG ODN as IIRMIs we showed that trace levels of these impurities synergized to induce IgM, IFNγ, TNFα and IL-6 expression. In vivo, trace levels of these impurities synergized to increase antigen-specific IgG antibodies to ovalbumin. Further, whereas mice treated with human erythropoietin showed a transient increase in hematocrit, those that received human erythropoietin containing low levels of IIRMIs had reduced response to erythropoietin after the 1(st dose and developed long-lasting anemia following subsequent doses. This suggests that the presence of IIRMIs facilitated a breach in tolerance to the endogenous mouse erythropoietin. Overall, these studies indicate that the risk of enhancing immunogenicity should be considered when establishing acceptance limits of IIRMIs for therapeutic proteins.

  18. Moderate variations in CDC25B protein levels modulate the response to DNA damaging agents

    International Nuclear Information System (INIS)

    Aressy, B.; Bugler, B.; Valette, A.; Ducommun, B.; Biard, D.

    2008-01-01

    CDC25B, one of the three members of the CDC25 dual-specificity phosphatase family, plays a critical role in the control of the cell cycle and in the checkpoint response to DNA damage. CDC25B is responsible for the initial dephosphorylation and activation of the cyclin-dependent kinases, thus initiating the train of events leading to entry into mitosis. The critical role played by CDC25B is illustrated by the fact that it is specifically required for checkpoint recovery and that unscheduled accumulation of CDC25B is responsible for illegitimate entry into mitosis. Here, we report that in p53 colon carcinoma cells, a moderate increase in the CDC25B level is sufficient to impair the DNA damage checkpoint, to increase spontaneous mutagenesis, and to sensitize cells to ionising radiation and genotoxic agents. Using a tumour cell spheroid assay as an alternative to animal studies, we demonstrate that the level of CDC25B expression modulates growth inhibition and apoptotic death. Since CDC25B overexpression has been observed in a significant number of human cancers, including colon carcinoma, and is often associated with high grade tumours and poor prognosis, our work suggests that the expression level of CDC25B might be a potential key parameter of the cellular response to cancer therapy. (authors)

  19. Low level light in combination with metabolic modulators for effective therapy

    Science.gov (United States)

    Dong, Tingting; Zhang, Qi; Hamblin, Michael R.; Wu, Mei X.

    2015-03-01

    Vascular damage occurs frequently at the injured brain causing hypoxia and is associated with poor outcomes in the clinics. We found high levels of glycolysis, reduced ATP generation, and increased formation of reactive oxygen species (ROS) and apoptosis in neurons under hypoxia. Strikingly, these adverse events were reversed significantly by noninvasive exposure of injured brain to low-level light (LLL). LLL illumination sustained the mitochondrial membrane potential, constrained cytochrome C leakage in hypoxic cells, and protected them from apoptosis, underscoring a unique property of LLL. The effect of LLL was further bolstered by combination with metabolic substrates such as pyruvate or lactate both in vivo and in vitro. The combinational treatment retained memory and learning activities of injured mice to a normal level, whereas those treated with LLL or pyruvate alone, or sham light displayed partial or severe deficiency in these cognitive functions. In accordance with well-protected learning and memory function, the hippocampal region primarily responsible for learning and memory was completely protected by a combination of LLL and pyruvate, in marked contrast to the severe loss of hippocampal tissue due to secondary damage in control mice. These data clearly suggest that energy metabolic modulators can additively or synergistically enhance the therapeutic effect of LLL in energy-producing insufficient tissues like injured brain. Keywords:

  20. Two discrete components of the 20 Hz steady-state response are distinguished through the modulation of activation level

    DEFF Research Database (Denmark)

    Griskova, Inga; Mørup, Morten; Parnas, Josef

    2009-01-01

    Objective: To investigate the modulation of amplitude and phase precision of the auditory steady-state response (SSR) to 20 Hz stimulation in two conditions varying in the level of activation. Methods: Click stimuli (20 Hz) were applied while subjects were sitting upright silently reading a book......-negative multi-way factorization (NMWF). Results: The NMWF decomposition of amplitude and phase precision measures resulted in the observation of two distinct components: a component at the frequency of stimulation – 20 Hz SSR and a component emerging at 40 Hz – 20 Hz SSR-related 40 Hz activity. Modulation...... by the activation level was observed only for 20 Hz SSR-related 40 Hz activity as increased amplitude and phase precision during low activation level. No such effects were observed for 20 Hz SSR. Conclusion: The discrete components of the 20 Hz SSR are distinguished through modulation of activation level, 20 Hz SSR...

  1. High fat diet and inflammation - modulation of Haptoglobin level in rat brain

    Directory of Open Access Journals (Sweden)

    Maria Stefania eSpagnuolo

    2015-12-01

    Full Text Available Obesity and dietary fats are well known risk factors for the pathogenesis of neurodegenerative diseases. The analysis of specific markers, whose brain level can be affected by diet, might contribute to unveil the intersection between inflammation/obesity and neurodegeneration. Haptoglobin (Hpt is an acute phase protein, which acts as antioxidant by binding free Haemoglobin (Hb, thus neutralizing its pro-oxidative action. We previously demonstrated that Hpt plays critical functions in brain, modulating cholesterol trafficking in neuroblastoma cell lines, beta-amyloid (Aβ uptake by astrocyte, and limiting Aβ toxicity on these cells. A major aim of this study was to evaluate whether a long term (12 or 24 weeks high-fat diet (HFD influences Hpt and Hb expression in rat hippocampus. We also assessed the development of obesity-induced inflammation by measuring hippocampal level of TNF-alpha, and the extent of protein oxidation by titrating nitro-tyrosine (N-Tyr. Hpt concentration was lower (p<0.001 in hippocampus of HFD rats than in control animals, both in the 12 and in the 24 weeks fed groups. HFD was also associated in hippocampus with the increase of Hb level (p<0.01, inflammation and protein oxidative modification, as evidenced by the increase in the concentration of TNF-alpha and nitro-tyrosine. In fact, TNF-alpha concentration was higher in rats receiving HFD for 12 (p<0.01 or 24 weeks (p<0.001 compared to those receiving the control diet. N-Tyr concentration was more elevated in hippocampus of HFD than in control rats in both 12 weeks (p=0.04 and 24 weeks groups (p=0.01, and a positive correlation between Hb and N-Tyr concentration was found in each group. Finally, we found that the treatment of the human glioblastoma-astrocytoma cell line U-87 MG with cholesterol and fatty acids, such as palmitic and linoleic acid, significantly impairs (p<0.001 Hpt secretion in the extracellular compartment.We hypothesize that the HFD-dependent decrease of

  2. A Comprehensive Investigation on the Short Circuit Performance of MW-level IGBT Power Modules

    DEFF Research Database (Denmark)

    Wu, Rui; Reigosa, Paula Diaz; Iannuzzo, Francesco

    2015-01-01

    This paper investigates the short circuit performance of commercial 1.7 kV / 1 kA IGBT power modules by means of a 6 kA Non-Destructive-Tester. A mismatched current distribution among the parallel chips has been observed, which can reduce the short circuit capability of the IGBT power module unde...... short circuit conditions. Further Spice simulations reveal that the stray parameters inside the module play an important role in contributing to such a phenomenon....

  3. Screening with an NMNAT2-MSD platform identifies small molecules that modulate NMNAT2 levels in cortical neurons.

    Science.gov (United States)

    Ali, Yousuf O; Bradley, Gillian; Lu, Hui-Chen

    2017-03-07

    Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a key neuronal maintenance factor and provides potent neuroprotection in numerous preclinical models of neurological disorders. NMNAT2 is significantly reduced in Alzheimer's, Huntington's, Parkinson's diseases. Here we developed a Meso Scale Discovery (MSD)-based screening platform to quantify endogenous NMNAT2 in cortical neurons. The high sensitivity and large dynamic range of this NMNAT2-MSD platform allowed us to screen the Sigma LOPAC library consisting of 1280 compounds. This library had a 2.89% hit rate, with 24 NMNAT2 positive and 13 negative modulators identified. Western analysis was conducted to validate and determine the dose-dependency of identified modulators. Caffeine, one identified NMNAT2 positive-modulator, when systemically administered restored NMNAT2 expression in rTg4510 tauopathy mice to normal levels. We confirmed in a cell culture model that four selected positive-modulators exerted NMNAT2-specific neuroprotection against vincristine-induced cell death while four selected NMNAT2 negative modulators reduced neuronal viability in an NMNAT2-dependent manner. Many of the identified NMNAT2 positive modulators are predicted to increase cAMP concentration, suggesting that neuronal NMNAT2 levels are tightly regulated by cAMP signaling. Taken together, our findings indicate that the NMNAT2-MSD platform provides a sensitive phenotypic screen to detect NMNAT2 in neurons.

  4. Modulation of neurological related allergic reaction in mice exposed to low-level toluene

    International Nuclear Information System (INIS)

    Tin-Tin-Win-Shwe; Yamamoto, Shoji; Nakajima, Daisuke; Furuyama, Akiko; Fukushima, Atsushi; Ahmed, Sohel; Goto, Sumio; Fujimaki, Hidekazu

    2007-01-01

    The contributing role of indoor air pollution to the development of allergic disease has become increasingly evident in public health problems. It has been reported that extensive communication exists between neurons and immune cells, and neurotrophins are molecules potentially responsible for regulating and controlling this neuroimmune crosstalk. The adverse effects of volatile organic compounds which are main indoor pollutants on induction or augmentation of neuroimmune interaction have not been fully characterized yet. To investigate the effects of low-level toluene inhalation on the airway inflammatory responses, male C3H mice were exposed to filtered air (control), 9 ppm, and 90 ppm toluene for 30 min by nose-only inhalation on Days 0, 1, 2, 7, 14, 21, and 28. Some groups of mice were injected with ovalbumin intraperitoneally before starting exposure schedule and these mice were then challenged with aerosolized ovalbumin as booster dose. For analysis of airway inflammation, bronchoalveolar lavage (BAL) fluid were collected to determine inflammatory cell influx and lung tissue and blood samples were collected to determine cytokine and neurotrophin mRNA and protein expressions and plasma antibody titers using real-time RT-PCR and ELISA methods respectively. Exposure of the ovalbumin-immunized mice to low-level toluene resulted in (1) increased inflammatory cells infiltration in BAL fluid; (2) increased IL-5 mRNA, decreased nerve growth factor receptor tropomyosin-related kinase A and brain-derived neurotrophic factor mRNAs in lung; and (3) increased IgE and IgG 1 antibodies and nerve growth factor content in the plasma. These findings suggest that low-level toluene exposure aggravates the airway inflammatory responses in ovalbumin-immunized mice by modulating neuroimmune crosstalk

  5. Reproductive parameters and mitochondrial function in spermatozoa of F1 and F2 minipig boars transgenic for n-terminal part of the human mutated huntingtin

    Czech Academy of Sciences Publication Activity Database

    Mačáková, Monika; Hansíková, H.; Pavlok, Antonín; Hajková, Z.; Sádková, J.; Juhás, Štefan; Juhásová, Jana; Baxa, Monika; Zeman, J.; Motlík, Jan

    2012-01-01

    Roč. 83, Suppl 1 (2012), A16-A16 ISSN 0022-3050. [European Huntington´s disease network 2012 plenary meeting. 14.09.2012-16.09.2012, Stockholm] R&D Projects: GA TA ČR TA01011466 Institutional support: RVO:67985904 Keywords : huntingtin Subject RIV: EB - Genetics ; Molecular Biology

  6. Folding Landscape of Mutant Huntingtin Exon1: Diffusible Multimers, Oligomers and Fibrils, and No Detectable Monomer.

    Directory of Open Access Journals (Sweden)

    Bankanidhi Sahoo

    Full Text Available Expansion of the polyglutamine (polyQ track of the Huntingtin (HTT protein above 36 is associated with a sharply enhanced risk of Huntington's disease (HD. Although there is general agreement that HTT toxicity resides primarily in N-terminal fragments such as the HTT exon1 protein, there is no consensus on the nature of the physical states of HTT exon1 that are induced by polyQ expansion, nor on which of these states might be responsible for toxicity. One hypothesis is that polyQ expansion induces an alternative, toxic conformation in the HTT exon1 monomer. Alternative hypotheses posit that the toxic species is one of several possible aggregated states. Defining the nature of the toxic species is particularly challenging because of facile interconversion between physical states as well as challenges to identifying these states, especially in vivo. Here we describe the use of fluorescence correlation spectroscopy (FCS to characterize the detailed time and repeat length dependent self-association of HTT exon1-like fragments both with chemically synthesized peptides in vitro and with cell-produced proteins in extracts and in living cells. We find that, in vitro, mutant HTT exon1 peptides engage in polyQ repeat length dependent dimer and tetramer formation, followed by time dependent formation of diffusible spherical and fibrillar oligomers and finally by larger, sedimentable amyloid fibrils. For expanded polyQ HTT exon1 expressed in PC12 cells, monomers are absent, with tetramers being the smallest molecular form detected, followed in the incubation time course by small, diffusible aggregates at 6-9 hours and larger, sedimentable aggregates that begin to build up at 12 hrs. In these cell cultures, significant nuclear DNA damage appears by 6 hours, followed at later times by caspase 3 induction, mitochondrial dysfunction, and cell death. Our data thus defines limits on the sizes and concentrations of different physical states of HTT exon1 along the

  7. Level of processing modulates the neural correlates of emotional memory formation

    Science.gov (United States)

    Ritchey, Maureen; LaBar, Kevin S.; Cabeza, Roberto

    2010-01-01

    Emotion is known to influence multiple aspects of memory formation, including the initial encoding of the memory trace and its consolidation over time. However, the neural mechanisms whereby emotion impacts memory encoding remain largely unexplored. The present study employed a levels-of-processing manipulation to characterize the impact of emotion on encoding with and without the influence of elaborative processes. Participants viewed emotionally negative, neutral, and positive scenes under two conditions: a shallow condition focused on the perceptual features of the scenes and a deep condition that queried their semantic meaning. Recognition memory was tested 2 days later. Results showed that emotional memory enhancements were greatest in the shallow condition. FMRI analyses revealed that the right amygdala predicted subsequent emotional memory in the shallow more than deep condition, whereas the right ventrolateral prefrontal cortex demonstrated the reverse pattern. Furthermore, the association of these regions with the hippocampus was modulated by valence: the amygdala-hippocampal link was strongest for negative stimuli, whereas the prefrontal-hippocampal link was strongest for positive stimuli. Taken together, these results suggest two distinct activation patterns underlying emotional memory formation: an amygdala component that promotes memory during shallow encoding, especially for negative information, and a prefrontal component that provides extra benefits during deep encoding, especially for positive information. PMID:20350176

  8. Level of processing modulates the neural correlates of emotional memory formation.

    Science.gov (United States)

    Ritchey, Maureen; LaBar, Kevin S; Cabeza, Roberto

    2011-04-01

    Emotion is known to influence multiple aspects of memory formation, including the initial encoding of the memory trace and its consolidation over time. However, the neural mechanisms whereby emotion impacts memory encoding remain largely unexplored. The present study used a levels-of-processing manipulation to characterize the impact of emotion on encoding with and without the influence of elaborative processes. Participants viewed emotionally negative, neutral, and positive scenes under two conditions: a shallow condition focused on the perceptual features of the scenes and a deep condition that queried their semantic meaning. Recognition memory was tested 2 days later. Results showed that emotional memory enhancements were greatest in the shallow condition. fMRI analyses revealed that the right amygdala predicted subsequent emotional memory in the shallow more than deep condition, whereas the right ventrolateral PFC demonstrated the reverse pattern. Furthermore, the association of these regions with the hippocampus was modulated by valence: the amygdala-hippocampal link was strongest for negative stimuli, whereas the prefrontal-hippocampal link was strongest for positive stimuli. Taken together, these results suggest two distinct activation patterns underlying emotional memory formation: an amygdala component that promotes memory during shallow encoding, especially for negative information, and a prefrontal component that provides extra benefits during deep encoding, especially for positive information.

  9. Laterality of brain activity during motor imagery is modulated by the provision of source level neurofeedback.

    Science.gov (United States)

    Boe, Shaun; Gionfriddo, Alicia; Kraeutner, Sarah; Tremblay, Antoine; Little, Graham; Bardouille, Timothy

    2014-11-01

    Motor imagery (MI) may be effective as an adjunct to physical practice for motor skill acquisition. For example, MI is emerging as an effective treatment in stroke neurorehabilitation. As in physical practice, the repetitive activation of neural pathways during MI can drive short- and long-term brain changes that underlie functional recovery. However, the lack of feedback about MI performance may be a factor limiting its effectiveness. The provision of feedback about MI-related brain activity may overcome this limitation by providing the opportunity for individuals to monitor their own performance of this endogenous process. We completed a controlled study to isolate neurofeedback as the factor driving changes in MI-related brain activity across repeated sessions. Eighteen healthy participants took part in 3 sessions comprised of both actual and imagined performance of a button press task. During MI, participants in the neurofeedback group received source level feedback based on activity from the left and right sensorimotor cortex obtained using magnetoencephalography. Participants in the control group received no neurofeedback. MI-related brain activity increased in the sensorimotor cortex contralateral to the imagined movement across sessions in the neurofeedback group, but not in controls. Task performance improved across sessions but did not differ between groups. Our results indicate that the provision of neurofeedback during MI allows healthy individuals to modulate regional brain activity. This finding has the potential to improve the effectiveness of MI as a tool in neurorehabilitation. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Modulation of genetic associations with serum urate levels by body-mass-index in humans.

    Directory of Open Access Journals (Sweden)

    Jennifer E Huffman

    Full Text Available We tested for interactions between body mass index (BMI and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, Pinter= 2.6 x 10-8. Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDARADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10-8, a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10-8, regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10-4. Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment.

  11. LRP5 and plasma cholesterol levels modulate the canonical Wnt pathway in peripheral blood leukocytes.

    Science.gov (United States)

    Borrell-Pages, Maria; Carolina Romero, July; Badimon, Lina

    2015-08-01

    Inflammation is triggered after invasion or injury to restore homeostasis. Although the activation of Wnt/β-catenin signaling is one of the first molecular responses to cellular damage, its role in inflammation is still unclear. It was our hypothesis that the low-density lipoprotein (LDL) receptor-related protein 5 (LRP5) and the canonical Wnt signaling pathway are modulators of inflammatory mechanisms. Wild-type (WT) and LRP5(-/-) mice were fed a hypercholesterolemic (HC) diet to trigger dislipidemia and chronic inflammation. Diets were supplemented with plant sterol esters (PSEs) to induce LDL cholesterol lowering and the reduction of inflammation. HC WT mice showed increased serum cholesterol levels that correlated with increased Lrp5 and Wnt/β-catenin gene expression while in the HC LRP5(-/-) mice Wnt/β-catenin pathway was shut down. Functionally, HC induced pro-inflammatory gene expression in LRP5(-/-) mice, suggesting an inhibitory role of the Wnt pathway in inflammation. Dietary PSE administration downregulated serum cholesterol levels in WT and LRP5(-/-) mice. Furthermore, in WT mice PSE increased anti-inflammatory genes expression and inhibited Wnt/β-catenin activation. Hepatic gene expression of Vldlr, Lrp2 and Lrp6 was increased after HC feeding in WT mice but not in LRP5(-/-) mice, suggesting a role for these receptors in the clearance of plasmatic lipoproteins. Finally, an antiatherogenic role for LRP5 was demonstrated as HC LRP5(-/-) mice developed larger aortic atherosclerotic lesions than WT mice. Our results show an anti-inflammatory, pro-survival role for LRP5 and the Wnt signaling pathway in peripheral blood leukocytes.

  12. MO-AB-BRA-01: A Global Level Set Based Formulation for Volumetric Modulated Arc Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, D; Lyu, Q; Ruan, D; O’Connor, D; Low, D; Sheng, K [Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA (United States)

    2016-06-15

    Purpose: The current clinical Volumetric Modulated Arc Therapy (VMAT) optimization is formulated as a non-convex problem and various greedy heuristics have been employed for an empirical solution, jeopardizing plan consistency and quality. We introduce a novel global direct aperture optimization method for VMAT to overcome these limitations. Methods: The global VMAT (gVMAT) planning was formulated as an optimization problem with an L2-norm fidelity term and an anisotropic total variation term. A level set function was used to describe the aperture shapes and adjacent aperture shapes were penalized to control MLC motion range. An alternating optimization strategy was implemented to solve the fluence intensity and aperture shapes simultaneously. Single arc gVMAT plans, utilizing 180 beams with 2° angular resolution, were generated for a glioblastoma multiforme (GBM), lung (LNG), and 2 head and neck cases—one with 3 PTVs (H&N3PTV) and one with 4 PTVs (H&N4PTV). The plans were compared against the clinical VMAT (cVMAT) plans utilizing two overlapping coplanar arcs. Results: The optimization of the gVMAT plans had converged within 600 iterations. gVMAT reduced the average max and mean OAR dose by 6.59% and 7.45% of the prescription dose. Reductions in max dose and mean dose were as high as 14.5 Gy in the LNG case and 15.3 Gy in the H&N3PTV case. PTV coverages (D95, D98, D99) were within 0.25% of the prescription dose. By globally considering all beams, the gVMAT optimizer allowed some beams to deliver higher intensities, yielding a dose distribution that resembles a static beam IMRT plan with beam orientation optimization. Conclusions: The novel VMAT approach allows for the search of an optimal plan in the global solution space and generates deliverable apertures directly. The single arc VMAT approach fully utilizes the digital linacs’ capability in dose rate and gantry rotation speed modulation. Varian Medical Systems, NIH grant R01CA188300, NIH grant R43CA183390.

  13. dNTP pool levels modulate mutator phenotypes of error-prone DNA polymerase ε variants.

    Science.gov (United States)

    Williams, Lindsey N; Marjavaara, Lisette; Knowels, Gary M; Schultz, Eric M; Fox, Edward J; Chabes, Andrei; Herr, Alan J

    2015-05-12

    Mutator phenotypes create genetic diversity that fuels tumor evolution. DNA polymerase (Pol) ε mediates leading strand DNA replication. Proofreading defects in this enzyme drive a number of human malignancies. Here, using budding yeast, we show that mutator variants of Pol ε depend on damage uninducible (Dun)1, an S-phase checkpoint kinase that maintains dNTP levels during a normal cell cycle and up-regulates dNTP synthesis upon checkpoint activation. Deletion of DUN1 (dun1Δ) suppresses the mutator phenotype of pol2-4 (encoding Pol ε proofreading deficiency) and is synthetically lethal with pol2-M644G (encoding altered Pol ε base selectivity). Although pol2-4 cells cycle normally, pol2-M644G cells progress slowly through S-phase. The pol2-M644G cells tolerate deletions of mediator of the replication checkpoint (MRC) 1 (mrc1Δ) and radiation sensitive (Rad) 9 (rad9Δ), which encode mediators of checkpoint responses to replication stress and DNA damage, respectively. The pol2-M644G mutator phenotype is partially suppressed by mrc1Δ but not rad9Δ; neither deletion suppresses the pol2-4 mutator phenotype. Thus, checkpoint activation augments the Dun1 effect on replication fidelity but is not required for it. Deletions of genes encoding key Dun1 targets that negatively regulate dNTP synthesis, suppress the dun1Δ pol2-M644G synthetic lethality and restore the mutator phenotype of pol2-4 in dun1Δ cells. DUN1 pol2-M644G cells have constitutively high dNTP levels, consistent with checkpoint activation. In contrast, pol2-4 and POL2 cells have similar dNTP levels, which decline in the absence of Dun1 and rise in the absence of the negative regulators of dNTP synthesis. Thus, dNTP pool levels correlate with Pol ε mutator severity, suggesting that treatments targeting dNTP pools could modulate mutator phenotypes for therapy.

  14. PSCAD modeling of a two-level space vector pulse width modulation algorithm for power electronics education

    Directory of Open Access Journals (Sweden)

    Ahmet Mete Vural

    2016-09-01

    Full Text Available This paper presents the design details of a two-level space vector pulse width modulation algorithm in PSCAD that is able to generate pulses for three-phase two-level DC/AC converters with two different switching patterns. The presented FORTRAN code is generic and can be easily modified to meet many other kinds of space vector modulation strategies. The code is also editable for hardware programming. The new component is tested and verified by comparing its output as six gating signals with those of a similar component in MATLAB library. Moreover the component is used to generate digital signals for closed-loop control of STATCOM for reactive power compensation in PSCAD. This add-on can be an effective tool to give students better understanding of the space vector modulation algorithm for different control tasks in power electronics area, and can motivate them for learning.

  15. Space Vector Pulse Width Modulation Strategy for Single-Phase Three-Level CIC T-source Inverter

    DEFF Research Database (Denmark)

    Shults, Tatiana E.; Husev, Oleksandr O.; Blaabjerg, Frede

    2016-01-01

    This paper presents a novel space vector pulse-width modulation strategy for a single-phase three-level buck-boost inverter based on an impedance-source network. The case study system is based on T-source inverter with continuous input current. To demonstrate the improved performance of the inver......This paper presents a novel space vector pulse-width modulation strategy for a single-phase three-level buck-boost inverter based on an impedance-source network. The case study system is based on T-source inverter with continuous input current. To demonstrate the improved performance...... of the inverter, the strategy was compared the traditional pulse-width modulation. It is shown that the approach proposed has fewer switching states and does not suffer from neutral point misbalance....

  16. Fractal analysis for assessing the level of modulation of IMRT fields

    International Nuclear Information System (INIS)

    Nauta, Marcel; Villarreal-Barajas, J. Eduardo; Tambasco, Mauro

    2011-01-01

    Purpose: To investigate the potential of three fractal dimension (FD) analysis methods (i.e., the variation, power spectrum, and variogram methods) as metrics for quantifying the degree of modulation in planned intensity modulated radiation therapy (IMRT) treatment fields, and compare the most suitable FD method to the number of monitor units (MUs), the average leaf gap, and the 2D modulation index (2D MI) for assessing modulation. Methods: The authors implemented, validated, and compared the variation, power spectrum, and variogram methods for computing the FD. Validation of the methods was done using mathematical fractional Brownian surfaces of known FD that ranged in size from 128 x 128 to 512 x 512. The authors used a test set consisting of seven head and neck carcinoma plans (50 prescribed treatment fields) to choose an FD cut-point that ensures no false positives (100% specificity) in distinguishing between moderate and high degrees of field modulation. The degree of field modulation was controlled by adjusting the fluence smoothing parameters in the Eclipse treatment planning system (Varian Medical Systems, Palo Alto, CA). The moderate modulation fields were representative of the degree of modulation used clinically at the authors' institution. The authors performed IMRT quality assurance (QA) on the 50 test fields using the MapCHECK device. The FD cut-point was applied to a validation set consisting of four head and neck plans (28 fields). The area under the curve (AUC) from receiver operating characteristic (ROC) analysis was used to compare the ability of FD, number of MUs, average leaf gap, and the 2D MI for distinguishing between the moderate and high modulation fields. Results: The authors found the variogram FD method to be the most suitable for assessing the modulation complexity of IMRT fields for head and neck carcinomas. Pass rates as measured by the gamma criterion for the MapCHECK IMRT field measurements were higher for the moderately modulated

  17. Carrier-based modulation schemes for various three-level matrix converters

    DEFF Research Database (Denmark)

    Blaabjerg, Frede; Loh, P.C.; Rong, R.C.

    2008-01-01

    different performance merits. To avoid confusion and hence fasten the converter applications in the industry, it would surely be better for modulation schemes to be developed from a common set of modulation principles that unfortunately has not yet been thoroughly defined. Contributing to that area...... a limited set of switching vectors because of its lower semiconductor count. Through simulation and experimental testing, all the evaluated matrix converters are shown to produce satisfactory sinusoidal input and output quantities using the same set of generic modulation principles, which can conveniently...

  18. Development of Chemistry Triangle Oriented Module on Topic of Reaction Rate for Senior High School Level Grade XI Chemistry Learning.

    Science.gov (United States)

    Sari, D. R.; Hardeli; Bayharti

    2018-04-01

    This study aims to produce chemistry triangle oriented module on topic of reaction rate, and to reveal the validity and practicality level of the generated module. The type of research used is EducationalDesign Research (EDR) with development model is Plompmodel. This model consists of three phases, which are preliminary research, prototyping phase, and assessment phase. The instrument used in this research is questionnaire validity and practicality. The data of the research were analyzed by using Kappa Cohen formula. The chemistry triangle oriented module validation sheet was given to 5 validators consisting of 3 chemistry lecturers and 2 high school chemistry teachers, while the practicality sheet was given to 2 chemistry teachers, 6 students of SMAN 10 Padang grade XII MIA 5 on the small groupevaluation and 25 students of SMAN 10 Padang grade XII MIA 6 on the field test. Based on the questionnaire validity analysis, the validity level of the module is very high with the value of kappa moment 0.87. The level of practicality based on teacher questionnaire response is very high category with a kappa moment value 0.96. Based on the questionnaire of student responses on small group evaluation, the level of practicality is very high category with a kappa moment 0.81, and the practicality is very high category with kappa moment value 0.83 based on questionnaire of student response on field test.

  19. Positive lysosomal modulation as a unique strategy to treat age-related protein accumulation diseases.

    Science.gov (United States)

    Bahr, Ben A; Wisniewski, Meagan L; Butler, David

    2012-04-01

    Lysosomes are involved in degrading and recycling cellular ingredients, and their disruption with age may contribute to amyloidogenesis, paired helical filaments (PHFs), and α-synuclein and mutant huntingtin aggregation. Lysosomal cathepsins are upregulated by accumulating proteins and more so by the modulator Z-Phe-Ala-diazomethylketone (PADK). Such positive modulators of the lysosomal system have been studied in the well-characterized hippocampal slice model of protein accumulation that exhibits the pathogenic cascade of tau aggregation, tubulin breakdown, microtubule destabilization, transport failure, and synaptic decline. Active cathepsins were upregulated by PADK; Rab proteins were modified as well, indicating enhanced trafficking, whereas lysosome-associated membrane protein and proteasome markers were unchanged. Lysosomal modulation reduced the pre-existing PHF deposits, restored tubulin structure and transport, and recovered synaptic components. Further proof-of-principle studies used Alzheimer disease mouse models. It was recently reported that systemic PADK administration caused dramatic increases in cathepsin B protein and activity levels, whereas neprilysin, insulin-degrading enzyme, α-secretase, and β-secretase were unaffected by PADK. In the transgenic models, PADK treatment resulted in clearance of intracellular amyloid beta (Aβ) peptide and concomitant reduction of extracellular deposits. Production of the less pathogenic Aβ(1-38) peptide corresponded with decreased levels of Aβ(1-42), supporting the lysosome's antiamyloidogenic role through intracellular truncation. Amelioration of synaptic and behavioral deficits also indicates a neuroprotective function of the lysosomal system, identifying lysosomal modulation as an avenue for disease-modifying therapies. From the in vitro and in vivo findings, unique lysosomal modulators represent a minimally invasive, pharmacologically controlled strategy against protein accumulation disorders to enhance

  20. A Temperature-Dependent Thermal Model of IGBT Modules Suitable for Circuit-Level Simulations

    DEFF Research Database (Denmark)

    Wu, Rui; Wang, Huai; Ma, Ke

    2014-01-01

    Thermal impedance of IGBT modules may vary with operating conditions due to that the thermal conductivity and heat capacity of materials are temperature dependent. This paper proposes a Cauer thermal model for a 1700 V/1000 A IGBT module with temperature-dependent thermal resistances and thermal ...... relevant reliability aspect performance. A test bench is built up with an ultra-fast infrared (IR) camera to validate the proposed thermal impedance model....

  1. Environmental factors as modulators of neurodegeneration: insights from gene-environment interactions in Huntington's disease.

    Science.gov (United States)

    Mo, Christina; Hannan, Anthony J; Renoir, Thibault

    2015-05-01

    Unlike many other neurodegenerative diseases with established gene-environment interactions, Huntington's disease (HD) is viewed as a disorder governed by genetics. The cause of the disease is a highly penetrant tandem repeat expansion encoding an extended polyglutamine tract in the huntingtin protein. In the year 2000, a pioneering study showed that the disease could be delayed in transgenic mice by enriched housing conditions. This review describes subsequent human and preclinical studies identifying environmental modulation of motor, cognitive, affective and other symptoms found in HD. Alongside the behavioral observations we also discuss potential mechanisms and the relevance to other neurodegenerative disorders, including Alzheimer's and Parkinson's disease. In mouse models of HD, increased sensorimotor and cognitive stimulation can delay or ameliorate various endophenotypes. Potential mechanisms include increased trophic support, synaptic plasticity, adult neurogenesis, and other forms of experience-dependent cellular plasticity. Subsequent clinical investigations support a role for lifetime activity levels in modulating the onset and progression of HD. Stress can accelerate memory and olfactory deficits and exacerbate cellular dysfunctions in HD mice. In the absence of effective treatments to slow the course of HD, environmental interventions offer feasible approaches to delay the disease, however further preclinical and human studies are needed in order to generate clinical recommendations. Environmental interventions could be combined with future pharmacological therapies and stimulate the identification of enviromimetics, drugs which mimic or enhance the beneficial effects of cognitive stimulation and physical activity. Copyright © 2015. Published by Elsevier Ltd.

  2. New Modulation Strategy to Balance the Neutral-Point Voltage for Three-Level Neutral-Clamped Inverter Systems

    DEFF Research Database (Denmark)

    Choi, Uimin; Lee, June-Seok; Lee, Kyo-Beum

    2014-01-01

    This paper proposes a new modulation strategy that balances the neutral-point voltage for three-level neutral-clamped inverter systems. The proposed modulation replaces the P-type or N-type small switching states with other switching states that do not affect the neutral-point voltage. The zero...... and medium switching states are employed to help the neutral-point voltage balancing. This method little bit increases the switching events and output total harmonic distortion. However, this method has a strong balancing ability at all regions. Further, it is very simple to implement in both space vector...

  3. Enhanced 2/3 four-ary modulation code using soft-decision Viterbi decoding for four-level holographic data storage systems

    Science.gov (United States)

    Kong, Gyuyeol; Choi, Sooyong

    2017-09-01

    An enhanced 2/3 four-ary modulation code using soft-decision Viterbi decoding is proposed for four-level holographic data storage systems. While the previous four-ary modulation codes focus on preventing maximum two-dimensional intersymbol interference patterns, the proposed four-ary modulation code aims at maximizing the coding gains for better bit error rate performances. For achieving significant coding gains from the four-ary modulation codes, we design a new 2/3 four-ary modulation code in order to enlarge the free distance on the trellis through extensive simulation. The free distance of the proposed four-ary modulation code is extended from 1.21 to 2.04 compared with that of the conventional four-ary modulation code. The simulation result shows that the proposed four-ary modulation code has more than 1 dB gains compared with the conventional four-ary modulation code.

  4. A novel humanized mouse model of Huntington disease for preclinical development of therapeutics targeting mutant huntingtin alleles

    DEFF Research Database (Denmark)

    Southwell, Amber L; Skotte, Niels H; Villanueva, Erika B

    2017-01-01

    transgenes in Hu128/21 mice match the human HTT exon 1 reference sequence. Conversely, the BACHD transgene carries a floxed, synthetic exon 1 sequence. Hu128/21 mice will be useful for investigations of human HTT that cannot be addressed in Hu97/18 mice, for developing therapies targeted to exon 1......Huntington disease (HD) is a neurodegenerative disease caused by a mutation in the huntingtin (HTT) gene. HTT is a large protein, interacts with many partners and is involved in many cellular pathways, which are perturbed in HD. Therapies targeting HTT directly are likely to provide the most global......-length, genomic human HTT transgenes heterozygous for the HD mutation and polymorphisms associated with HD in populations of East Asian descent and in a minority of patients from other ethnic groups. Hu128/21 mice display a wide variety of HD-like phenotypes that are similar to YAC128 mice. Additionally, both...

  5. Huntingtin-interacting protein 14 is a type 1 diabetes candidate protein regulating insulin secretion and β-cell apoptosis

    DEFF Research Database (Denmark)

    Berchtold, Lukas Adrian; Størling, Zenia Marian; Ortis, Fernanda

    2011-01-01

    Type 1 diabetes (T1D) is a complex disease characterized by the loss of insulin-secreting β-cells. Although the disease has a strong genetic component, and several loci are known to increase T1D susceptibility risk, only few causal genes have currently been identified. To identify disease...... genes in T1D, including the INS gene. An unexpected top-scoring candidate gene was huntingtin-interacting protein (HIP)-14/ZDHHC17. Immunohistochemical analysis of pancreatic sections demonstrated that HIP14 is almost exclusively expressed in insulin-positive cells in islets of Langerhans. RNAi...... knockdown experiments established that HIP14 is an antiapoptotic protein required for β-cell survival and glucose-stimulated insulin secretion. Proinflammatory cytokines (IL-1β and IFN-γ) that mediate β-cell dysfunction in T1D down-regulated HIP14 expression in insulin-secreting INS-1 cells and in isolated...

  6. Thermal Equilibrium Dynamic Control Based on DPWM Dual-Mode Modulation of High Power NPC Three-Level Inverter

    Directory of Open Access Journals (Sweden)

    Shi-Zhou Xu

    2016-01-01

    Full Text Available In some special applications of NPC three-level inverters, such as mine hoist, there exist special conditions of overloading during the whole hoisting process and large overload in starting stage, during which the power-loss calculation of power devices and thermal control are important factors affecting the thermal stability of inverters. The principles of SVPWM and DPWM were described in this paper firstly, based on which the dynamic power losses of the two modulations of hoist in single period were calculated. Secondly, a thermal equilibrium dynamic control based on DPMW dual-mode modulation was proposed, which can switch the modulation dynamically according to the change of dynamic power loss to realize dynamic control of power loss and thermal equilibrium of inverter. Finally, simulation and experiment prove the effectiveness of the proposed strategy.

  7. Optical polarization modulation by competing atomic coherence effects in a degenerate four-level Yb atomic system

    International Nuclear Information System (INIS)

    Park, Sung Jong; Park, Chang Yong; Yoon, Tai Hyun

    2005-01-01

    A scheme of optical polarization modulation of a linearly polarized infrared probe field is studied in a degenerate four-level Yb atomic system. We have observed an anomalous transmission spectra of two circular polarization components of the probe field exhibiting an enhanced two-photon absorption and a three-photon gain with comparable magnitude, leading to the lossless transmission and enhanced circular dichroism. We carried out a proof-of-principle experiment of fast optical polarization modulation in such a system by modulating the polarization state of the coupling field. The observed enhanced two-photon absorption and three-photon gain of the probe field are due to the result of competing atomic coherence effects

  8. Huntingtin-associated protein-1 (HAP1) regulates endocytosis and interacts with multiple trafficking-related proteins.

    Science.gov (United States)

    Mackenzie, Kimberly D; Lim, Yoon; Duffield, Michael D; Chataway, Timothy; Zhou, Xin-Fu; Keating, Damien J

    2017-07-01

    Huntingtin-associated protein 1 (HAP1) was initially identified as a binding partner of huntingtin, mutations in which underlie Huntington's disease. Subcellular localization and protein interaction data indicate that HAP1 may be important in vesicle trafficking, cell signalling and receptor internalization. In this study, a proteomics approach was used for the identification of novel HAP1-interacting partners to attempt to shed light on the physiological function of HAP1. Using affinity chromatography with HAP1-GST protein fragments bound to Sepharose columns, this study identified a number of trafficking-related proteins that bind to HAP1. Interestingly, many of the proteins that were identified by mass spectrometry have trafficking-related functions and include the clathrin light chain B and Sec23A, an ER to Golgi trafficking vesicle coat component. Using co-immunoprecipitation and GST-binding assays the association between HAP1 and clathrin light chain B has been validated in vitro. This study also finds that HAP1 co-localizes with clathrin light chain B. In line with a physiological function of the HAP1-clathrin interaction this study detected a dramatic reduction in vesicle retrieval and endocytosis in adrenal chromaffin cells. Furthermore, through examination of transferrin endocytosis in HAP1 -/- cortical neurons, this study has determined that HAP1 regulates neuronal endocytosis. In this study, the interaction between HAP1 and Sec23A was also validated through endogenous co-immunoprecipitation in rat brain homogenate. Through the identification of novel HAP1 binding partners, many of which have putative trafficking roles, this study provides us with new insights into the mechanisms underlying the important physiological function of HAP1 as an intracellular trafficking protein through its protein-protein interactions. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Attention, working memory, and phenomenal experience of WM content: memory levels determined by different types of top-down modulation.

    Science.gov (United States)

    Jacob, Jane; Jacobs, Christianne; Silvanto, Juha

    2015-01-01

    What is the role of top-down attentional modulation in consciously accessing working memory (WM) content? In influential WM models, information can exist in different states, determined by allocation of attention; placing the original memory representation in the center of focused attention gives rise to conscious access. Here we discuss various lines of evidence indicating that such attentional modulation is not sufficient for memory content to be phenomenally experienced. We propose that, in addition to attentional modulation of the memory representation, another type of top-down modulation is required: suppression of all incoming visual information, via inhibition of early visual cortex. In this view, there are three distinct memory levels, as a function of the top-down control associated with them: (1) Nonattended, nonconscious associated with no attentional modulation; (2) attended, phenomenally nonconscious memory, associated with attentional enhancement of the actual memory trace; (3) attended, phenomenally conscious memory content, associated with enhancement of the memory trace and top-down suppression of all incoming visual input.

  10. An FMEA evaluation of intensity modulated radiation therapy dose delivery failures at tolerance criteria levels.

    Science.gov (United States)

    Faught, Jacqueline Tonigan; Balter, Peter A; Johnson, Jennifer L; Kry, Stephen F; Court, Laurence E; Stingo, Francesco C; Followill, David S

    2017-11-01

    The objective of this work was to assess both the perception of failure modes in Intensity Modulated Radiation Therapy (IMRT) when the linac is operated at the edge of tolerances given in AAPM TG-40 (Kutcher et al.) and TG-142 (Klein et al.) as well as the application of FMEA to this specific section of the IMRT process. An online survey was distributed to approximately 2000 physicists worldwide that participate in quality services provided by the Imaging and Radiation Oncology Core - Houston (IROC-H). The survey briefly described eleven different failure modes covered by basic quality assurance in step-and-shoot IMRT at or near TG-40 (Kutcher et al.) and TG-142 (Klein et al.) tolerance criteria levels. Respondents were asked to estimate the worst case scenario percent dose error that could be caused by each of these failure modes in a head and neck patient as well as the FMEA scores: Occurrence, Detectability, and Severity. Risk probability number (RPN) scores were calculated as the product of these scores. Demographic data were also collected. A total of 181 individual and three group responses were submitted. 84% were from North America. Most (76%) individual respondents performed at least 80% clinical work and 92% were nationally certified. Respondent medical physics experience ranged from 2.5 to 45 yr (average 18 yr). A total of 52% of individual respondents were at least somewhat familiar with FMEA, while 17% were not familiar. Several IMRT techniques, treatment planning systems, and linear accelerator manufacturers were represented. All failure modes received widely varying scores ranging from 1 to 10 for occurrence, at least 1-9 for detectability, and at least 1-7 for severity. Ranking failure modes by RPN scores also resulted in large variability, with each failure mode being ranked both most risky (1st) and least risky (11th) by different respondents. On average MLC modeling had the highest RPN scores. Individual estimated percent dose errors and severity

  11. Decreased modulation by the risk level on the brain activation during decision making in adolescents with internet gaming disorder

    Directory of Open Access Journals (Sweden)

    Xin eQi

    2015-11-01

    Full Text Available Greater impulse and risk-taking and reduced decision-making ability were reported as the main behavioral impairments in individuals with Internet gaming disorder (IGD, which has become a serious mental health issue worldwide. However, it is not clear to date how the risk level modulates brain activity during the decision-making process in IGD individuals. In this study, 23 adolescents with IGD and 24 healthy controls (HCs without IGD were recruited, and the Balloon Analog Risk Task (BART was used in a functional magnetic resonance imaging (fMRI experiment to evaluate the modulation of the risk level (the probability of balloon explosion on brain activity during risky decisionmaking in IGD adolescents. Reduced modulation of the risk level on the activation of the right dorsolateral prefrontal cortex (DLPFC during the active BART was found in IGD group compared to the HCs. In the IGD group, there was a significant negative correlation between the risk-related DLPFC activation during the active BART and the Barratt impulsivity scale (BIS-11 scores, which were significantly higher in IGD group compared with the HCs. Our study demonstrated that, as a critical decision-making-related brain region, the right DLPFC is less sensitive to risk in IGD adolescents compared with the HCs, which may contribute to the higher impulsivity level in IGD adolescents.

  12. What Factors Promote Student Resilience on a Level 1 Distance Learning Module?

    Science.gov (United States)

    Simons, Joan; Beaumont, Kythe; Holland, Lesley

    2018-01-01

    Resilience is understood to be the ability to adapt positively in the face of adversity. In relation to new students on a distance learning module, this can mean how they adapt and make sense of the demands of their chosen study to enable them to persist in their studies. This article reports a small-scale study involving semi-structured telephone…

  13. Travel and Tourism Module. An Advanced-Level Option For Distribution and Marketing.

    Science.gov (United States)

    New York State Education Dept., Albany. Bureau of Occupational Education Curriculum Development.

    Intended as an advanced option for distributive education students in the twelfth grade, this travel and tourism module is designed to cover a minimum of ten weeks or a maximum of twenty weeks. Introductory material includes information on employment demands, administrative considerations, course format, teaching suggestions, expected outcomes,…

  14. Thermal Equilibrium Dynamic Control Based on DPWM Dual-Mode Modulation of High Power NPC Three-Level Inverter

    OpenAIRE

    Xu, Shi-Zhou; He, Feng-You

    2016-01-01

    In some special applications of NPC three-level inverters, such as mine hoist, there exist special conditions of overloading during the whole hoisting process and large overload in starting stage, during which the power-loss calculation of power devices and thermal control are important factors affecting the thermal stability of inverters. The principles of SVPWM and DPWM were described in this paper firstly, based on which the dynamic power losses of the two modulations of hoist in single pe...

  15. Structural modulation of brain development by oxygen: evidence on adolescents migrating from high altitude to sea level environment.

    Science.gov (United States)

    Zhang, Jiaxing; Zhang, Haiyan; Chen, Ji; Fan, Ming; Gong, Qiyong

    2013-01-01

    The present study aimed to investigate structural modulation of brain by high level of oxygen during its peak period of development. Voxel-based morphometry analysis of gray matter (GM) and white matter (WM) volumes and Tract-Based Spatial Statistics analysis of WM fractional anisotropy (FA) and mean diffusion (MD) based on MRI images were carried out on 21 Tibetan adolencents (15-18 years), who were born and raised in Qinghai-Tibetan Plateau (2900-4700 m) and have lived at sea level (SL) in the last 4 years. The control group consisted of matched Tibetan adolescents born and raised at high altitude all the time. SL immigrants had increased GM volume in the left insula, left inferior parietal gyrus, and right superior parietal gyrus and decreased GM in the left precentral cortex and multiple sites in cerebellar cortex (left lobule 8, bilateral lobule 6 and crus 1/2). Decreased WM volume was found in the right superior frontal gyrus in SL immigrants. SL immigrants had higher FA and lower MD at multiple sites of WM tracts. Moreover, we detected changes in ventilation and circulation. GM volume in cerebellum lobule 8 positively correlated with diastolic pressure, while GM volume in insula positively correlated vital capacity and hypoxic ventilatory response. Our finding indicate that the structural modulations of GM by high level of oxygen during its peak period of development are related to respiratory and circulatory regulations, while the modulation in WM mainly exhibits an enhancement in myelin maturation.

  16. Modulated Raman Spectroscopy for Enhanced Cancer Diagnosis at the Cellular Level

    Science.gov (United States)

    De Luca, Anna Chiara; Dholakia, Kishan; Mazilu, Michael

    2015-01-01

    Raman spectroscopy is emerging as a promising and novel biophotonics tool for non-invasive, real-time diagnosis of tissue and cell abnormalities. However, the presence of a strong fluorescence background is a key issue that can detract from the use of Raman spectroscopy in routine clinical care. The review summarizes the state-of-the-art methods to remove the fluorescence background and explores recent achievements to address this issue obtained with modulated Raman spectroscopy. This innovative approach can be used to extract the Raman spectral component from the fluorescence background and improve the quality of the Raman signal. We describe the potential of modulated Raman spectroscopy as a rapid, inexpensive and accurate clinical tool to detect the presence of bladder cancer cells. Finally, in a broader context, we show how this approach can greatly enhance the sensitivity of integrated Raman spectroscopy and microfluidic systems, opening new prospects for portable higher throughput Raman cell sorting. PMID:26110401

  17. Cells exposed to a huntingtin fragment containing an expanded polyglutamine tract show no sign of ion channel formation: results arguing against the ion channel hypothesis

    DEFF Research Database (Denmark)

    Nørremølle, Anne; Grunnet, Morten; Hasholt, Lis

    2003-01-01

    Ion channels formed by expanded polyglutamine tracts have been proposed to play an important role in the pathological processes leading to neurodegeneration in Huntington's disease and other CAG repeat diseases. We tested the capacity of a huntingtin fragment containing an expanded polyglutamine...... in the currents recorded in any of the two expression systems, indicating no changes in ion channel activity. The results therefore argue against the proposed hypothesis of expanded polyglutamines forming ion channels....

  18. Mass spektrometry-based SRM assay for quantification of human mutant huntingtin protein in a transgenic minipig model of Huntington´s disease

    Czech Academy of Sciences Publication Activity Database

    Kotrčová, Eva; Suchá, Rita; Tylečková, Jiřina; Dresler, J.; Kovářová, Hana

    2015-01-01

    Roč. 78, Suppl 2 (2015), s. 17-17 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA TA ČR(CZ) TA01011466; GA MŠk ED2.1.00/03.0124; GA MŠk(CZ) 7F14308 Institutional support: RVO:67985904 Keywords : huntingtin gene Subject RIV: FH - Neurology

  19. Characterization of the Transient Response of the ILS with One Module Installed to Heatup Changes in Power Level and Cooldown

    International Nuclear Information System (INIS)

    K. G. Condie; C. M. Stoots; J. E. O'Brien; J. S. Herring

    2007-01-01

    This report provides documentation of the initial startup and testing of the first electrolysis module in the Idaho National Laboratory (INL) High Temperature Steam Electrolysis Integrated Laboratory Scale (ILS) facility. Initial shakedown testing of the INL ILS experimental facility commenced on August 22, 2007. This fulfilled a DOE Level 2 milestone. Heatup of the first ILS module started at approximately 4:10 PM on September 24, 2007. Initial module testing continued for 420 hours. The test average H2 production rate was approximately 1.3 Nm3/hr (0.116 kg H2/hr), with a peak measured value of over 2 Nm3/hr (0.179 kg H2/hr). Significant module performance degradation was observed over the first 250 hours, after which no further degradation was noted for the remainder of the test. Once all test objectives had been successfully met, the test was terminated in a controlled fashion. Discussion is included concerning several modifications that will be incorporated into the facility components to improve reliability and ease of operation for future long term testing

  20. Periodically Swapping Modulation (PSM) Strategy for Three-Level (TL) DC/DC Converter with Balanced Switch Currents

    DEFF Research Database (Denmark)

    Liu, Dong; Deng, Fujin; Zhang, Qi

    2018-01-01

    The asymmetrical modulation strategy is widely used in various types of three-level (TL) DC/DC converters, while the current imbalance among the power switches is one of the important issues. In this paper, a novel periodically swapping modulation (PSM) strategy is proposed for balancing the power...... switches’ currents in various types of TL DC/DC converters. In the proposed PSM strategy, the driving signals of the switch pairs are swapped periodically, which guarantees that the currents through the power switches are kept balanced in every two switching periods. Therefore, the proposed PSM...... strategy can effectively improve the reliability of the converter by balancing the power losses and thermal stresses among the power switches. The operation principle and performances of the proposed PSM strategy are analyzed in detail. Finally, the simulation and experimental results are presented...

  1. space vector pulse width modulation of a multi-level diode clamped

    African Journals Online (AJOL)

    ES Obe

    step by step development of MATLAB /SIMULINK modeling of the space vector ..... Pulse Width Mod. of Multi-Level Diode Clamped Converter 119 powergui. Discrete, .... Load. Figure 22: Block diagram of the three level DCC design. 3 LEVEL ...

  2. Ghrelin-related peptides do not modulate vasodilator nitric oxide production or superoxide levels in mouse systemic arteries.

    Science.gov (United States)

    Ku, Jacqueline M; Sleeman, Mark W; Sobey, Christopher G; Andrews, Zane B; Miller, Alyson A

    2016-04-01

    The ghrelin gene is expressed in the stomach where it ultimately encodes up to three peptides, namely, acylated ghrelin, des-acylated ghrelin and obestatin, which all have neuroendocrine roles. Recently, the authors' reported that these peptides have important physiological roles in positively regulating vasodilator nitric oxide (NO) production in the cerebral circulation, and may normally suppress superoxide production by the pro-oxidant enzyme, Nox2-NADPH oxidase. To date, the majority of studies using exogenous peptides infer that they may have similar roles in the systemic circulation. Therefore, this study examined whether exogenous and endogenous ghrelin-related peptides modulate NO production and superoxide levels in mouse mesenteric arteries and/or thoracic aorta. Using wire myography, it was found that application of exogenous acylated ghrelin, des-acylated ghrelin or obestatin to mouse thoracic aorta or mesenteric arteries failed to elicit a vasorelaxation response, whereas all three peptides elicited vasorelaxation responses of rat thoracic aorta. Also, none of the peptides modulated mouse aortic superoxide levels as measured by L-012-enhanced chemiluminescence. Next, it was found that NO bioactivity and superoxide levels were unaffected in the thoracic aorta from ghrelin-deficient mice when compared with wild-type mice. Lastly, using novel GHSR-eGFP reporter mice in combination with double-labelled immunofluorescence, no evidence was found for the growth hormone secretagogue receptor (GHSR1a) in the throracic aorta, which is the only functional ghrelin receptor identified to date. Collectively these findings demonstrate that, in contrast to systemic vessels of other species (e.g. rat and human) and mouse cerebral vessels, ghrelin-related peptides do not modulate vasodilator NO production or superoxide levels in mouse systemic arteries. © 2016 John Wiley & Sons Australia, Ltd.

  3. Antiandrogens act as selective androgen receptor modulators at the proteome level in prostate cancer cells.

    Science.gov (United States)

    Brooke, Greg N; Gamble, Simon C; Hough, Michael A; Begum, Shajna; Dart, D Alwyn; Odontiadis, Michael; Powell, Sue M; Fioretti, Flavia M; Bryan, Rosie A; Waxman, Jonathan; Wait, Robin; Bevan, Charlotte L

    2015-05-01

    Current therapies for prostate cancer include antiandrogens, inhibitory ligands of the androgen receptor, which repress androgen-stimulated growth. These include the selective androgen receptor modulators cyproterone acetate and hydroxyflutamide and the complete antagonist bicalutamide. Their activity is partly dictated by the presence of androgen receptor mutations, which are commonly detected in patients who relapse while receiving antiandrogens, i.e. in castrate-resistant prostate cancer. To characterize the early proteomic response to these antiandrogens we used the LNCaP prostate cancer cell line, which harbors the androgen receptor mutation most commonly detected in castrate-resistant tumors (T877A), analyzing alterations in the proteome, and comparing these to the effect of these therapeutics upon androgen receptor activity and cell proliferation. The majority are regulated post-transcriptionally, possibly via nongenomic androgen receptor signaling. Differences detected between the exposure groups demonstrate subtle changes in the biological response to each specific ligand, suggesting a spectrum of agonistic and antagonistic effects dependent on the ligand used. Analysis of the crystal structures of the AR in the presence of cyproterone acetate, hydroxyflutamide, and DHT identified important differences in the orientation of key residues located in the AF-2 and BF-3 protein interaction surfaces. This further implies that although there is commonality in the growth responses between androgens and those antiandrogens that stimulate growth in the presence of a mutation, there may also be influential differences in the growth pathways stimulated by the different ligands. This therefore has implications for prostate cancer treatment because tumors may respond differently dependent upon which mutation is present and which ligand is activating growth, also for the design of selective androgen receptor modulators, which aim to elicit differential proteomic

  4. Dialkylthio Substitution: An Effective Method to Modulate the Molecular Energy Levels of 2D-BDT Photovoltaic Polymers.

    Science.gov (United States)

    Yao, Huifeng; Zhang, Hao; Ye, Long; Zhao, Wenchao; Zhang, Shaoqing; Hou, Jianhui

    2016-02-17

    Dialkylthio-substituted thienyl-benzodithiophene (BDT-DST) was designed and synthesized as a building block to modulate the molecular levels of the conjugated polymers, and three copolymers named PDST-BDD, PDST-TT and PDST-DPP were prepared and applied in polymer solar cells (PSCs). Theoretical calculations and electrochemical cyclic voltammetry (CV) measurement suggested that the dialkylthio group could decrease the molecular energy levels of the resulting polymers distinctly. The open-circuit voltage (VOC) of PSC devices based on PDST-BDD, PDST-TT, and PDST-DPP are as high as 1.0, 0.98, and 0.88 V, respectively, which are ∼0.15 V higher than those of the corresponding alky-substituted analogues. Moreover, the influence of the dialkylthio group on the absorption spectra, crystalline properties, hole mobilities, and blend morphologies of the polymers was also investigated. The results indicate that the dialkythio substitution is an effective method to modulate the molecular energy levels and that the BDT-DST unit has potential for constructing high-efficiency photovoltaic polymers.

  5. The Kynurenine Pathway Modulates Neurodegeneration in a Drosophila Model of Huntington’s Disease

    Science.gov (United States)

    Campesan, Susanna; Green, Edward W.; Breda, Carlo; Sathyasaikumar, Korrapati V.; Muchowski, Paul J.; Schwarcz, Robert; Kyriacou, Charalambos P.; Giorgini, Flaviano

    2014-01-01

    Summary Neuroactive metabolites of the kynurenine pathway (KP) of tryptophan degradation have been implicated in the pathophysiology of neurodegenerative disorders, including Huntington’s disease (HD) [1]. A central hallmark of HD is neurodegeneration caused by a polyglutamine expansion in the huntingtin (htt) protein [2]. Here we exploit a transgenic Drosophila melanogaster model of HD to interrogate the therapeutic potential of KP manipulation. We observe that genetic and pharmacological inhibition of kynurenine 3-monooxygenase (KMO) increases levels of the neuroprotective metabolite kynurenic acid (KYNA) relative to the neurotoxic metabolite 3-hydroxykynurenine (3-HK) and ameliorates neurodegeneration. We also find that genetic inhibition of tryptophan 2,3-dioxygenase (TDO), the first and rate-limiting step in the pathway, leads to a similar neuroprotective shift toward KYNA synthesis. Importantly, we demonstrate that the feeding of KYNA and 3-HK to HD model flies directly modulates neurodegeneration, underscoring the causative nature of these metabolites. This study provides the first genetic evidence that inhibition of KMO and TDO activity protects against neurodegenerative disease in an animal model, indicating that strategies targeted at two key points within the KP may have therapeutic relevance in HD, and possibly other neurodegenerative disorders. PMID:21636279

  6. Enhanced Cross-Phase Modulation Based on a Double Electromagnetically Induced Transparency in a Four-Level Tripod Atomic System

    International Nuclear Information System (INIS)

    Li Shujing; Yang Xudong; Cao Xuemin; Zhang Chunhong; Xie Changde; Wang Hai

    2008-01-01

    We report experimental observations on the simultaneous electromagnetically induced transparency (EIT) effects for probe and trigger fields (double EIT) as well as the enhanced cross-phase modulation (XPM) between the two fields in a four-level tripod EIT system of the D1 line of 87 Rb atoms. The XPM coefficients (larger than 2x10 -5 cm 2 /W) and the accompanying transmissions (higher than 60%) are measured at a slight detuning of the probe field from the exact EIT-resonance condition. The system and enhanced cross-Kerr nonlinearities presented here can be applied to quantum information processes

  7. Striking similarity in the gene expression levels of individual Myc module members among ESCs, EpiSCs, and partial iPSCs.

    Directory of Open Access Journals (Sweden)

    Masataka Hirasaki

    Full Text Available Predominant transcriptional subnetworks called Core, Myc, and PRC modules have been shown to participate in preservation of the pluripotency and self-renewality of embryonic stem cells (ESCs. Epiblast stem cells (EpiSCs are another cell type that possesses pluripotency and self-renewality. However, the roles of these modules in EpiSCs have not been systematically examined to date. Here, we compared the average expression levels of Core, Myc, and PRC module genes between ESCs and EpiSCs. EpiSCs showed substantially higher and lower expression levels of PRC and Core module genes, respectively, compared with those in ESCs, while Myc module members showed almost equivalent levels of average gene expression. Subsequent analyses revealed that the similarity in gene expression levels of the Myc module between these two cell types was not just overall, but striking similarities were evident even when comparing the expression of individual genes. We also observed equivalent levels of similarity in the expression of individual Myc module genes between induced pluripotent stem cells (iPSCs and partial iPSCs that are an unwanted byproduct generated during iPSC induction. Moreover, our data demonstrate that partial iPSCs depend on a high level of c-Myc expression for their self-renewal properties.

  8. Modulation of plasma fibrinogen levels by ciprofibrate and gemfibrozil in primary hyperlipidaemia

    NARCIS (Netherlands)

    de Maat, M. P.; Knipscheer, H. C.; Kastelein, J. J.; Kluft, C.

    1997-01-01

    An elevated plasma fibrinogen level is increasingly accepted as an independent risk indicator of cardiovascular disease. This has enhanced the interest in identifying agents that can normalize elevated plasma fibrinogen levels. One group of agents with this capacity are the fibric acid derivatives,

  9. Spinal cord regeneration by modulating bone marrow with neurotransmitters and Citicholine: Analysis at micromolecular level.

    Science.gov (United States)

    Paulose, Cheramadathukudiyil Skaria; John, Ponnezhathu Sebastian; Chinthu, Romeo; Akhilraj, Puthenveetil Raju; Anju, Thoppil Raveendran

    2017-04-01

    Spinal cord injury results in disruption of brain-spinal cord fibre connectivity, leading to progressive tissue damage at the site of injury and resultant paralysis of varying degrees. The current study investigated the role of autologous bone marrow modulated with neurotransmitters and neurotransmitter stimulating agent, Citicholine, in spinal cord of spinal cord injured rats. Radioreceptor assay using [3H] ligand was carried out to quantify muscarinic receptor. Gene expression studies were done using Real Time PCR analysis. Scatchard analysis of muscarinic M1 receptor showed significantly decreased B max (p neurotransmitters combination along with bone marrow or Citicholine with bone marrow can reverse the muscarinic receptor alterations in the spinal cord of spinal cord injured rats, which is a promising step towards a better therapeutic intervention for spinal cord injury because of the positive role of cholinergic system in regulation of both locomotor activity and synaptic plasticity. Copyright © 2017 Chang Gung University. Published by Elsevier B.V. All rights reserved.

  10. Phosphofructokinase-P Modulates P44/42 MAPK Levels in HeLa Cells.

    Science.gov (United States)

    Cardim Pires, Thyago Rubens; Albanese, Jamille Mansur; Schwab, Michael; Marette, André; Carvalho, Renato Sampaio; Sola-Penna, Mauro; Zancan, Patricia

    2017-05-01

    It is known that interfering with glycolysis leads to profound modification of cancer cell proliferation. However, energy production is not the major reason for this correlation. Here, using HeLa cells as a model for cancer, we demonstrate that phosphofructokinase-P (PFK-P), which is overexpressed in diverse types of cancer including HeLa cells, modulates expression of P44/42 mitogen-activated protein kinase (MAPK). Silencing of PFK-P did not alter HeLa cell viability or energy production, including the glycolytic rate. On the other hand, silencing of PFK-P induced the downregulation of p44/42 MAPK, augmenting the sensitivity of HeLa cells to different drugs. Conversely, overexpression of PFK-P promotes the upregulation of p44/42 MAPK, making the cells more resistant to the drugs. These results indicate that overexpression of PFK-P by cancer cells is related to activation of survival pathways via upregulation of MAPK and suggest PFK-P as a promising target for cancer therapy. J. Cell. Biochem. 118: 1216-1226, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Modulating ectopic gene expression levels by using retroviral vectors equipped with synthetic promoters

    OpenAIRE

    Ferreira, Joshua P.; Peacock, Ryan W. S.; Lawhorn, Ingrid E. B.; Wang, Clifford L.

    2011-01-01

    The human cytomegalovirus and elongation factor 1α promoters are constitutive promoters commonly employed by mammalian expression vectors. These promoters generally produce high levels of expression in many types of cells and tissues. To generate a library of synthetic promoters capable of generating a range of low, intermediate, and high expression levels, the TATA and CAAT box elements of these promoters were mutated. Other promoter variants were also generated by random mutagenesis. Evalua...

  12. Solar Modulation of Atmospheric Cosmic Radiation:. Comparison Between In-Flight and Ground-Level Measurements

    Science.gov (United States)

    Iles, R. H. A.; Taylor, G. C.; Jones, J. B. L.

    January 2000 saw the start of a collaborative study involving the Mullard Space Science Laboratory, Virgin Atlantic Airways, the Civil Aviation Authority and the National Physical Laboratory in a program to investigate the cosmic radiation exposure to aircrew. The study has been undertaken in view of EU Directive 96/291 (May 2000) which requires the assessment of the level of radiation exposure to aircrew. The project's aims include validation of radiation dose models and evaluation of space weather effects on atmospheric cosmic radiation levels, in particular those effects not accounted for by the models. Ground level measurements are often used as a proxy for variations in cosmic radiation dose levels at aircraft altitudes, especially during Forbush Decreases (FDs) and Solar Energetic Particle (SEP) events. Is this estimation realistic and does the ground level data accurately represent what is happening at altitude? We have investigated the effect of a FD during a flight from Hong Kong to London Heathrow on the 15th July 2000 and compared count rate and dose measurements with simultaneous variations measured at ground level. We have also compared the results with model outputs.

  13. Effect of modulated ultrahigh frequency field on behavior and hormone level in female rats under emotional stress

    Energy Technology Data Exchange (ETDEWEB)

    Rasulov, M.M.

    The effect of a modulated electromagnetic field (MEMF) (field frequency of 40 MHz and modulated frequency of 50 Hz, 1 h exposure daily for 30 days) on behavior and level of sexual hormones, determined from the length of the estrous cycle and of its separate phases, was studied in female Wistar rats subjected to sexual deprivation. The ratio of frequency of running to number of vertical positions (R:V) was used as an index. Activity of rats declined during the 1-h exposure to MEMF; this may indicate the direct effect of MEMF on the central nervous system. Analysis of behavior after MEMF treatments ceased showed that the R:V ratio increased from 3.2:1 to 3:1 in month 3 and reached 2:1 in month 5. The relative significance of sexual behavior (lordosis, licking of perineum) more than double in comparison with the initial level. The findings support the existence of individual differences in sensitivity to a UHF field. The data on the estrous cycle indicate the tranquilizing effect of a UHF field on the neuroendocrine system and the greater resistance of individual animals exposed to MEMF to the development of sexual neurosis. 12 references, 2 figures.

  14. Modulating ectopic gene expression levels by using retroviral vectors equipped with synthetic promoters.

    Science.gov (United States)

    Ferreira, Joshua P; Peacock, Ryan W S; Lawhorn, Ingrid E B; Wang, Clifford L

    2011-12-01

    The human cytomegalovirus and elongation factor 1α promoters are constitutive promoters commonly employed by mammalian expression vectors. These promoters generally produce high levels of expression in many types of cells and tissues. To generate a library of synthetic promoters capable of generating a range of low, intermediate, and high expression levels, the TATA and CAAT box elements of these promoters were mutated. Other promoter variants were also generated by random mutagenesis. Evaluation using plasmid vectors integrated at a single site in the genome revealed that these various synthetic promoters were capable of expression levels spanning a 40-fold range. Retroviral vectors were equipped with the synthetic promoters and evaluated for their ability to reproduce the graded expression demonstrated by plasmid integration. A vector with a self-inactivating long terminal repeat could neither reproduce the full range of expression levels nor produce stable expression. Using a second vector design, the different synthetic promoters enabled stable expression over a broad range of expression levels in different cell lines. The online version of this article (doi:10.1007/s11693-011-9089-0) contains supplementary material, which is available to authorized users.

  15. Modulation of GDP-fucose level for generating proteins with reduced rate of fucosylation (WO2010141855).

    Science.gov (United States)

    Taupin, Philippe

    2011-09-01

    The application (WO2010141855) is in the field of glycobiology, and involves the control of the rate of fucosylation of proteins by exogenous factors. It aims at controlling the rate of protein fucosylation with inhibitors (drugs or nucleic acid antagonists) of enzymes involved in the synthesis of GDP-fucose. Mammalian cell lines were cultured in the presence of inhibitors, for example, siRNA. The rates of GDP-fucose in cells and during protein fucosylation were characterized. The level of protein fucosylation decreases rapidly in response to a decrease in GDP-fucose level. The relationship between the rate of fucosylation of proteins and the level of GDP-fucose in a cell is non-linear. Reduction in the rate of protein fucosylation can be achieved with a minimal reduction of the level of GDP-fucose in cells. The paradigm may be used to synthesize proteins and antibodies, with a reduced rate of fucosylation. The application claims that the use of drugs or nucleic acid antagonists that inhibit the enzymes involved in GDP-fucose biosynthesis optimizes the level of GDP-fucose present in cells, and reduces the rate of fucosylation of glycoproteins.

  16. Color and illuminance level of lighting can modulate willingness to eat bell peppers.

    Science.gov (United States)

    Hasenbeck, Aimee; Cho, Sungeun; Meullenet, Jean-François; Tokar, Tonya; Yang, Famous; Huddleston, Elizabeth A; Seo, Han-Seok

    2014-08-01

    Food products are often encountered under colored lighting, particularly in restaurants and retail stores. However, relatively little attention has been paid to whether the color of ambient lighting can affect consumers' motivation for consumption. This study aimed to determine whether color (Experiment 1) and illuminance level (Experiment 2) of lighting can influence consumers' liking of appearance and their willingness to eat bell peppers. For red, green, and yellow bell peppers, yellow and blue lighting conditions consistently increased participants' liking of appearance the most and the least, respectively. Participants' willingness to consume bell peppers increased the most under yellow lighting and the least under blue lighting. In addition, a dark condition (i.e. low level of lighting illuminance) decreased liking of appearance and willingness to eat the bell peppers compared to a bright condition (i.e. high level of lighting illuminance). Our findings demonstrate that lighting color and illuminance level can influence consumers' hedonic impression and likelihood to consume bell peppers. Furthermore, the influences of color and illuminance level of lighting appear to be dependent on the surface color of bell peppers. © 2013 Society of Chemical Industry.

  17. The Endocannabinoid System Modulating Levels of Consciousness, Emotions and Likely Dream Contents.

    Science.gov (United States)

    Murillo-Rodriguez, Eric; Pastrana-Trejo, Jose Carlos; Salas-Crisóstomo, Mireille; de-la-Cruz, Miriel

    2017-01-01

    indicate that the sleep-wake cycle is under the influence of endocannabinoids since the blocking of the CB1 cannabinoid receptor or the pharmacological inhibition of FAAH activity promotes wakefulness, whereas the obstruction of AMT function enhances sleep. However, no solid evidence is available regarding the role of the endocannabinoid system in an unquestionable emotional component of the sleep: Dream activity. Since dreaming is a mental activity that occurs during sleep (characterized by emotions, sensory perceptions, and bizarre components) and the endocannabinoid system modulates neurobiological processes involving consciousness, such as learning and memory, attention, pain perception, emotions and sleep, it is acceptable to hypothesize that the endocannabinoid system might be modulating dream activity. In this regard, an accumulative body of evidence in human and animal models has been reported regarding the role of the endocannabinoid system in the control of emotional states and dreams. Moreover, preliminary studies in humans have indicated that treatment with cannabinoids may decrease post-traumatic stress disorder symptoms, including nightmares. Thus, based on a review of the literature available in PubMed, this article hypothesizes a conceptual framework within which the endocannabinoid system might influence the generation of dream experiences. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Reverse-absorbance-modulation-optical lithography for optical nanopatterning at low light levels

    Energy Technology Data Exchange (ETDEWEB)

    Majumder, Apratim, E-mail: apratim.majumder@utah.edu; Wan, Xiaowen; Masid, Farhana; Menon, Rajesh [Department of Electrical and Computer Engineering, University of Utah, Salt Lake City, Utah 84112 (United States); Pollock, Benjamin J.; Andrew, Trisha L. [Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706 (United States); Soppera, Olivier [Mulhouse Institute for Material Sciences, CNRS LRC 7228, BP2488, Mulhouse 68200 (France)

    2016-06-15

    Absorbance-Modulation-Optical Lithography (AMOL) has been previously demonstrated to be able to confine light to deep sub-wavelength dimensions and thereby, enable patterning of features beyond the diffraction limit. In AMOL, a thin photochromic layer that converts between two states via light exposure is placed on top of the photoresist layer. The long wavelength photons render the photochromic layer opaque, while the short-wavelength photons render it transparent. By simultaneously illuminating a ring-shaped spot at the long wavelength and a round spot at the short wavelength, the photochromic layer transmits only a highly confined beam at the short wavelength, which then exposes the underlying photoresist. Many photochromic molecules suffer from a giant mismatch in quantum yields for the opposing reactions such that the reaction initiated by the absorption of the short-wavelength photon is orders of magnitude more efficient than that initiated by the absorption of the long-wavelength photon. As a result, large intensities in the ring-shaped spot are required for deep sub-wavelength nanopatterning. In this article, we overcome this problem by using the long-wavelength photons to expose the photoresist, and the short-wavelength photons to confine the “exposing” beam. Thereby, we demonstrate the patterning of features as thin as λ/4.7 (137 nm for λ = 647 nm) using extremely low intensities (4-30 W/m{sup 2}, which is 34 times lower than that required in conventional AMOL). We further apply a rigorous model to explain our experiments and discuss the scope of the reverse-AMOL process.

  19. Pulse width and height modulation for multi-level resistance in bi-layer TaOx based RRAM

    Science.gov (United States)

    Alamgir, Zahiruddin; Beckmann, Karsten; Holt, Joshua; Cady, Nathaniel C.

    2017-08-01

    Mutli-level switching in resistive memory devices enables a wide range of computational paradigms, including neuromorphic and cognitive computing. To this end, we have developed a bi-layer tantalum oxide based resistive random access memory device using Hf as the oxygen exchange layer. Multiple, discrete resistance levels were achieved by modulating the RESET pulse width and height, ranging from 2 kΩ to several MΩ. For a fixed pulse height, OFF state resistance was found to increase gradually with the increase in the pulse width, whereas for a fixed pulse width, the increase in the pulse height resulted in drastic changes in resistance. Resistive switching in these devices transitioned from Schottky emission in the OFF state to tunneling based conduction in the ON state, based on I-V curve fitting and temperature dependent current measurements. These devices also demonstrated endurance of more than 108 cycles with a satisfactory Roff/Ron ratio and retention greater than 104 s.

  20. γ-Secretase modulators reduce endogenous amyloid β42 levels in human neural progenitor cells without altering neuronal differentiation

    Science.gov (United States)

    D’Avanzo, Carla; Sliwinski, Christopher; Wagner, Steven L.; Tanzi, Rudolph E.; Kim, Doo Yeon; Kovacs, Dora M.

    2015-01-01

    Soluble γ-secretase modulators (SGSMs) selectively decrease toxic amyloid β (Aβ) peptides (Aβ42). However, their effect on the physiologic functions of γ-secretase has not been tested in human model systems. γ-Secretase regulates fate determination of neural progenitor cells. Thus, we studied the impact of SGSMs on the neuronal differentiation of ReNcell VM (ReN) human neural progenitor cells (hNPCs). Quantitative PCR analysis showed that treatment of neurosphere-like ReN cell aggregate cultures with γ-secretase inhibitors (GSIs), but not SGSMs, induced a 2- to 4-fold increase in the expression of the neuronal markers Tuj1 and doublecortin. GSI treatment also induced neuronal marker protein expression, as shown by Western blot analysis. In the same conditions, SGSM treatment selectively reduced endogenous Aβ42 levels by ∼80%. Mechanistically, we found that Notch target gene expressions were selectively inhibited by a GSI, not by SGSM treatment. We can assert, for the first time, that SGSMs do not affect the neuronal differentiation of hNPCs while selectively decreasing endogenous Aβ42 levels in the same conditions. Our results suggest that our hNPC differentiation system can serve as a useful model to test the impact of GSIs and SGSMs on both endogenous Aβ levels and γ-secretase physiologic functions including endogenous Notch signaling.—D’Avanzo, C., Sliwinski, C., Wagner, S. L., Tanzi, R. E., Kim, D. Y., Kovacs, D. M. γ-Secretase modulators reduce endogenous amyloid β42 levels in human neural progenitor cells without altering neuronal differentiation. PMID:25903103

  1. Quantification of modulated blood oxygenation levels in single cerebral veins by investigating their MR signal decay

    Energy Technology Data Exchange (ETDEWEB)

    Sedlacik, Jan [St. Jude Children' s Research Hospital, Memphis, TN (United States). Div. of Translational Imaging Research; University Clinics Jena (Germany). Medical Physics Group; Rauscher, Alexander [University Clinics Jena (Germany). Medical Physics Group; British Columbia Univ., Vancouver (Canada). MRI Research Centre; Reichenbach, Juergen R. [University Clinics Jena (Germany). Medical Physics Group

    2009-07-01

    The transverse magnetization of a single vein and its surrounding tissue is subject to spin dephasing caused by the local magnetic field inhomogeneity which is induced by the very same vessel. This phenomenon can be approximated and simulated by applying the model of an infinitely long and homogeneously magnetized cylinder embedded in a homogeneous tissue background. It is then possible to estimate the oxygenation level of the venous blood by fitting the simulated magnetization-time-course to the measured signal decay. In this work we demonstrate the ability of this approach to quantify the blood oxygenation level (Y) of small cerebral veins in vivo, not only under normal physiologic conditions (Y{sub native}=0.5-0.55) but also during induced changes of physiologic conditions which affect the cerebral venous blood oxygenation level. Changes of blood's oxygenation level induced by carbogen (5% CO{sub 2}, 95% O{sub 2}) and caffeine were observed and quantified, resulting in values of Y{sub carbogen}=0.7 and Y{sub caffeine}=0.42, respectively. The proposed technique may ultimately help to better understand local changes in cerebral physiology during neuronal activation by quantifying blood oxygenation in veins draining active brain areas. It may also be beneficial in clinical applications where it may improve diagnosis of cerebral pathologies as well as monitoring of responses to therapy. (orig.)

  2. Polymorphisms in FFAR4 (GPR120 Gene Modulate Insulin Levels and Sensitivity after Fish Oil Supplementation

    Directory of Open Access Journals (Sweden)

    Bastien Vallée Marcotte

    2017-11-01

    Full Text Available The objective was to test whether FFAR4 single nucleotide polymorphisms (SNPs are associated with glycemic control-related traits in humans following fish oil supplementation. A total of 210 participants were given 3 g/day of omega-3 (n-3 fatty acids (FA (1.9–2.2 g of eicosapentaenoic acid (EPA and 1.1 g of docosahexaenoic acid (DHA during six weeks. Biochemical parameters were taken before and after the supplementation. Using the HapMap database and the tagger procedure in Haploview, 12 tagging SNPs in FFAR4 were selected and then genotyped using TaqMan technology. Transcript expression levels were measured for 30 participants in peripheral mononuclear blood cells. DNA methylation levels were measured for 35 participants in leukocytes. In silico analyses were also performed. Four gene–diet interactions on fasting insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR index values were found. rs17108973 explained a significant proportion of the variance of insulin levels (3.0% and HOMA-IR (2.03% index values. Splice site prediction was different depending on the allele for rs11187527. rs17108973 and rs17484310 had different affinity for transcription factors depending on the allele. n-3 FAs effectively improve insulin-related traits for major allele homozygotes of four FFAR4 SNPs as opposed to carriers of the minor alleles.

  3. Level of Processing Modulates the Neural Correlates of Emotional Memory Formation

    Science.gov (United States)

    Ritchey, Maureen; LaBar, Kevin S.; Cabeza, Roberto

    2011-01-01

    Emotion is known to influence multiple aspects of memory formation, including the initial encoding of the memory trace and its consolidation over time. However, the neural mechanisms whereby emotion impacts memory encoding remain largely unexplored. The present study used a levels-of-processing manipulation to characterize the impact of emotion on…

  4. Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Jitendra Kumar

    Full Text Available Zinc is an essential trace metal that has integral roles in numerous biological processes, including enzymatic function, protein structure, and cell signaling pathways. Both excess and deficiency of zinc can lead to detrimental effects on development and metabolism, resulting in abnormalities and disease. We altered the zinc balance within Caenorhabditis elegans to examine how changes in zinc burden affect longevity and healthspan in an invertebrate animal model. We found that increasing zinc levels in vivo with excess dietary zinc supplementation decreased the mean and maximum lifespan, whereas reducing zinc levels in vivo with a zinc-selective chelator increased the mean and maximum lifespan in C. elegans. We determined that the lifespan shortening effects of excess zinc required expression of DAF-16, HSF-1 and SKN-1 proteins, whereas the lifespan lengthening effects of the reduced zinc may be partially dependent upon this set of proteins. Furthermore, reducing zinc levels led to greater nuclear localization of DAF-16 and enhanced dauer formation compared to controls, suggesting that the lifespan effects of zinc are mediated in part by the insulin/IGF-1 pathway. Additionally, zinc status correlated with several markers of healthspan in worms, including proteostasis, locomotion and thermotolerance, with reduced zinc levels always associated with improvements in function. Taken together, these data support a role for zinc in regulating both development and lifespan in C. elegans, and that suggest that regulation of zinc homeostasis in the worm may be an example of antagonistic pleiotropy.

  5. Modulation of genetic associations with serum urate levels by body-mass-index in humans

    NARCIS (Netherlands)

    J.E. Huffman (Jennifer); E. Albrecht (Eva); A. Teumer (Alexander); M. Mangino (Massimo); K. Kapur (Karen); T. Johnson (Toby); Z. Kutalik (Zoltán); N. Pirastu (Nicola); G. Pistis (Giorgio); L.M. Lopez (Lorna); T. Haller (Toomas); P. Salo (Perttu); A. Goel (Anuj); M. Li (Man); T. Tanaka (Toshiko); A. Dehghan (Abbas); D. Ruggiero; G. Malerba (Giovanni); A.V. Smith (Albert Vernon); Nolte, I.M. (Ilja M.); L. Portas (Laura); Phipps-Green, A. (Amanda); Boteva, L. (Lora); P. Navarro (Pau); A. Johansson (Åsa); A.A. Hicks (Andrew); O. Polasek (Ozren); T. Esko (Tõnu); J. Peden (John); S.E. Harris (Sarah); D. Murgia (Daniela); Wild, S.H. (Sarah H.); A. Tenesa (Albert); A. Tin (Adrienne); E. Mihailov (Evelin); A. Grotevendt (Anne); G.K. Gislason; J. Coresh (Josef); P. d' Adamo (Pio); S. Ulivi (Shelia); P. Vollenweider (Peter); G. Waeber (Gérard); Campbell, S. (Susan); I. Kolcic (Ivana); Fisher, K. (Krista); M. Viigimaa (Margus); Metter, J.E. (Jeffrey E.); C. Masciullo (Corrado); Trabetti, E. (Elisabetta); Bombieri, C. (Cristina); R. Sorice; A. Döring (Angela); G. Reischl (Gunilla); K. Strauch (Konstantin); A. Hofman (Albert); A.G. Uitterlinden (André); M. Waldenberger (Melanie); H.E. Wichmann (Heinz Erich); G. Davies (Gail); A.J. Gow (Alan J.); Dalbeth, N. (Nicola); Stamp, L. (Lisa); Smit, J.H. (Johannes H.); M. Kirin (Mirna); R. Nagaraja (Ramaiah); M. Nauck (Matthias); C. Schurmann (Claudia); K. Budde (Klemens); S.M. Farrington (Susan); E. Theodoratou (Evropi); A. Jula (Antti); V. Salomaa (Veikko); C. Sala (Cinzia); C. Hengstenberg (Christian); M. Burnier (Michel); Mägi, R. (Reedik); N. Klopp (Norman); S. Kloiber (Stefan); S. Schipf (Sabine); S. Ripatti (Samuli); Cabras, S. (Stefano); N. Soranzo (Nicole); G. Homuth (Georg); T. Nutile; P. Munroe (Patricia); N. Hastie (Nick); H. Campbell (H.); I. Rudan (Igor); Cabrera, C. (Claudia); Haley, C. (Chris); O.H. Franco (Oscar); Merriman, T.R. (Tony R.); V. Gudnason (Vilmundur); M. Pirastu (Mario); B.W.J.H. Penninx (Brenda); H. Snieder (Harold); A. Metspalu (Andres); M. Ciullo; P.P. Pramstaller (Peter Paul); C.M. van Duijn (Cornelia); L. Ferrucci (Luigi); G. Gambaro (Giovanni); Deary, I.J. (Ian J.); M.G. Dunlop (Malcolm); J.F. Wilson (James F); P. Gasparini (Paolo); U. Gyllensten (Ulf); T.D. Spector (Timothy); A.F. Wright (Alan); C. Hayward (Caroline); H. Watkins (Hugh); M. Perola (Markus); M. Bochud (Murielle); W.H.L. Kao (Wen); M. Caulfield (Mark); D. Toniolo (Daniela); H. Völzke (Henry); C. Gieger (Christian); A. Köttgen (Anna); V. Vitart (Veronique)

    2015-01-01

    textabstractWe tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in

  6. Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans

    NARCIS (Netherlands)

    Huffman, Jennifer E.; Albrecht, Eva; Teumer, Alexander; Mangino, Massimo; Kapur, Karen; Johnson, Toby; Kutalik, Zoltn; Pirastu, Nicola; Pistis, Giorgio; Lopez, Lorna M.; Haller, Toomas; Salo, Perttu; Goel, Anuj; Li, Man; Tanaka, Toshiko; Dehghan, Abbas; Ruggiero, Daniela; Malerba, Giovanni; Smith, Albert V.; Nolte, Ilja M.; Portas, Laura; Phipps-Green, Amanda; Boteva, Lora; Navarro, Pau; Johansson, Asa; Hicks, Andrew A.; Polasek, Ozren; Esko, Tonu; Peden, John F.; Harris, Sarah E.; Murgia, Federico; Wild, Sarah H.; Tenesa, Albert; Tin, Adrienne; Mihailov, Evelin; Grotevendt, Anne; Gislason, Gauti K.; Coresh, Josef; D'Adamo, Pio; Ulivi, Sheila; Vollenweider, Peter; Waeber, Gerard; Campbell, Susan; Kolcic, Ivana; Fisher, Krista; Viigimaa, Margus; Metter, Jeffrey E.; Masciullo, Corrado; Trabetti, Elisabetta; Bombieri, Cristina; Sorice, Rossella; Doering, Angela; Reischl, Eva; Strauch, Konstantin; Hofman, Albert; Uitterlinden, Andre G.; Waldenberger, Melanie; Wichmann, H-Erich; Davies, Gail; Gow, Alan J.; Dalbeth, Nicola; Stamp, Lisa; Smit, Johannes H.; Kirin, Mirna; Nagaraja, Ramaiah; Nauck, Matthias; Schurmann, Claudia; Budde, Kathrin; Farrington, Susan M.; Theodoratou, Evropi; Jula, Antti; Salomaa, Veikko; Sala, Cinzia; Hengstenberg, Christian; Burnier, Michel; Maegi, Reedik; Klopp, Norman; Kloiber, Stefan; Schipf, Sabine; Ripatti, Samuli; Cabras, Stefano; Soranzo, Nicole; Homuth, Georg; Nutile, Teresa; Munroe, Patricia B.; Hastie, Nicholas; Campbell, Harry; Rudan, Igor; Cabrera, Claudia; Haley, Chris; Franco, Oscar H.; Merriman, Tony R.; Gudnason, Vilmundur; Pirastu, Mario; Penninx, Brenda W.; Snieder, Harold; Metspalu, Andres; Ciullo, Marina; Pramstaller, Peter P.; van Duijn, Cornelia M.; Ferrucci, Luigi; Gambaro, Giovanni; Deary, Ian J.; Dunlop, Malcolm G.; Wilson, James F.; Gasparini, Paolo; Gyllensten, Ulf; Spector, Tim D.; Wright, Alan F.; Hayward, Caroline; Watkins, Hugh; Perola, Markus; Bochud, Murielle; Kao, W. H. Linda; Caulfield, Mark; Toniolo, Daniela; Voelzke, Henry; Gieger, Christian; Koettgen, Anna; Vitart, Veronique

    2015-01-01

    We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non

  7. Meteorologically induced modulation in sea level off Tikkavanipalem Coast - Central east coast of India

    Digital Repository Service at National Institute of Oceanography (India)

    Joseph, A.; Desai, R.G.P.; VijayKumar, K.; Mehra, P.; Nagvekar, S.

    on simultaneous observations of tidal and surface meteorological parameters in four temporal segments of 1-month duration each during a 1-year period in 1997-98. Sea level oscillations along the Tikkavanipalem segment of the central east coast of India contain...

  8. Light therapy modulates serotonin levels and blood flow in women with headache. A preliminary study.

    Science.gov (United States)

    Tomaz de Magalhães, Miriam; Núñez, Silvia Cristina; Kato, Ilka Tiemy; Ribeiro, Martha Simões

    2016-01-01

    In this study, we looked at the possible effects of low-level laser therapy (LLLT) on blood flow velocity, and serotonin (5-HT) and cholinesterase levels in patients with chronic headache associated with temporomandibular disorders (TMD). LLLT has been clinically applied over the past years with positive results in analgesia and without the report of any side effects. The understanding of biological mechanisms of action may improve clinical results and facilitate its indication. Ten patients presenting headache associated with TMD completed the study. An 830-nm infrared diode laser with power of 100 mW, exposure time of 34 s, and energy of 3.4 J was applied on the tender points of masseter and temporal muscle. Blood flow velocity was determined via ultrasound Doppler velocimetry before and after laser irradiation. The whole blood 5-HT and cholinesterase levels were evaluated three days before, immediately, and three days after laser irradiation. Pain score after treatment decreased to a score of 5.8 corresponding to 64% of pain reduction (P  0.05). Our findings indicated that LLLT regulates blood flow in the temporal artery after irradiation and might control 5-HT levels in patients suffering with tension-type headache associated to TMD contributing to pain relief. © 2016 by the Society for Experimental Biology and Medicine.

  9. cAMP level modulates scleral collagen remodeling, a critical step in the development of myopia.

    Directory of Open Access Journals (Sweden)

    Yijin Tao

    Full Text Available The development of myopia is associated with decreased ocular scleral collagen synthesis in humans and animal models. Collagen synthesis is, in part, under the influence of cyclic adenosine monophosphate (cAMP. We investigated the associations between cAMP, myopia development in guinea pigs, and collagen synthesis by human scleral fibroblasts (HSFs. Form-deprived myopia (FDM was induced by unilateral masking of guinea pig eyes. Scleral cAMP levels increased selectively in the FDM eyes and returned to normal levels after unmasking and recovery. Unilateral subconjunctival treatment with the adenylyl cyclase (AC activator forskolin resulted in a myopic shift accompanied by reduced collagen mRNA levels, but it did not affect retinal electroretinograms. The AC inhibitor SQ22536 attenuated the progression of FDM. Moreover, forskolin inhibited collagen mRNA levels and collagen secretion by HSFs. The inhibition was reversed by SQ22536. These results demonstrate a critical role of cAMP in control of myopia development. Selective regulation of cAMP to control scleral collagen synthesis may be a novel therapeutic strategy for preventing and treating myopia.

  10. Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans

    Science.gov (United States)

    Kumar, Jitendra; Barhydt, Tracy; Awasthi, Anjali; Lithgow, Gordon J.; Killilea, David W.; Kapahi, Pankaj

    2016-01-01

    Zinc is an essential trace metal that has integral roles in numerous biological processes, including enzymatic function, protein structure, and cell signaling pathways. Both excess and deficiency of zinc can lead to detrimental effects on development and metabolism, resulting in abnormalities and disease. We altered the zinc balance within Caenorhabditis elegans to examine how changes in zinc burden affect longevity and healthspan in an invertebrate animal model. We found that increasing zinc levels in vivo with excess dietary zinc supplementation decreased the mean and maximum lifespan, whereas reducing zinc levels in vivo with a zinc-selective chelator increased the mean and maximum lifespan in C. elegans. We determined that the lifespan shortening effects of excess zinc required expression of DAF-16, HSF-1 and SKN-1 proteins, whereas the lifespan lengthening effects of the reduced zinc may be partially dependent upon this set of proteins. Furthermore, reducing zinc levels led to greater nuclear localization of DAF-16 and enhanced dauer formation compared to controls, suggesting that the lifespan effects of zinc are mediated in part by the insulin/IGF-1 pathway. Additionally, zinc status correlated with several markers of healthspan in worms, including proteostasis, locomotion and thermotolerance, with reduced zinc levels always associated with improvements in function. Taken together, these data support a role for zinc in regulating both development and lifespan in C. elegans, and that suggest that regulation of zinc homeostasis in the worm may be an example of antagonistic pleiotropy. PMID:27078872

  11. Modulation of insulin-like growth factor 1 levels in human osteoarthritic subchondral bone osteoblasts.

    Science.gov (United States)

    Massicotte, Frédéric; Fernandes, Julio Cesar; Martel-Pelletier, Johanne; Pelletier, Jean-Pierre; Lajeunesse, Daniel

    2006-03-01

    Human osteoarthritis (OA) is characterized by cartilage loss, bone sclerosis, osteophyte formation and inflammation of the synovial membrane. We previously reported that OA osteoblasts (Ob) show abnormal phenotypic characteristics possibly responsible for bone sclerosis and that two subgroups of OA patients can be identified by low or high endogenous production of prostaglandin E2 (PGE2) by OA Ob. Here, we determined that the elevated PGE2 levels in the high OA subgroup were linked with enhanced cyclooxygenase-2 (COX-2) protein levels compared to normal and low OA Ob. A linear relationship was observed between endogenous PGE2 levels and insulin-like growth factor 1 (IGF-1) levels in OA Ob. As parathyroid hormone (PTH) and PGE2 are known stimulators of IGF-1 production in Ob, we next evaluated their effect in OA Ob. Both subgroups increased their IGF-1 production similarly in response to PGE2, while the high OA subgroup showed a blunted response to PTH compared to the low OA group. Conversely, only the high OA group showed a significant inhibition of IGF-1 production when PGE2 synthesis was reduced with Naproxen, a non-steroidal antiinflammatory drug (NSAID) that inhibits cyclooxygenases (COX). The PGE2-dependent stimulation of IGF-1 synthesis was due in part to the cAMP/protein kinase A pathway since both the direct inhibition of this pathway with H-89 and the inhibition of EP2 or EP4 receptors, linked to cAMP production, reduced IGF-1 synthesis. The production of the most abundant IGF-1 binding proteins (IGFBPs) in bone tissue, IGFBP-3, -4, and -5, was lower in OA compared to normal Ob independently of the OA group. Under basal condition, OA Ob expressed similar IGF-1 mRNA to normal Ob; however, PGE2 stimulated IGF-1 mRNA expression more in OA than normal Ob. These data suggest that increased IGF-1 levels correlate with elevated endogenous PGE2 levels in OA Ob and that higher IGF-1 levels in OA Ob could be important for bone sclerosis in OA.

  12. Modulation of plasma N-acylethanolamine levels and physiological parameters by dietary fatty acid composition in humans.

    Science.gov (United States)

    Jones, Peter J H; Lin, Lin; Gillingham, Leah G; Yang, Haifeng; Omar, Jaclyn M

    2014-12-01

    N-Acylethanolamines (NAEs) are endogenous lipid-signaling molecules involved in satiety and energetics; however, how diet impacts circulating NAE concentrations and their downstream metabolic actions in humans remains unknown. Objectives were to examine effects of diets enriched with high-oleic canola oil (HOCO) or HOCO blended with flaxseed oil (FXCO), compared with a Western diet (WD), on plasma NAE levels and the association with energy expenditure and substrate oxidation. Using a randomized controlled crossover design, 36 hypercholesterolemic participants consumed three isoenergetic diets for 28 days, each containing 36% energy from fat, of which 70% was HOCO, FXCO, or WD. Ultra-performance liquid chromatography-MS/MS was used to measure plasma NAE levels and indirect calorimetry to assess energy expenditure and substrate oxidation. After 28 days, compared with WD, plasma oleoylethanolamide (OEA) and alpha-linolenoyl ethanolamide (ALEA) levels were significantly increased in response to HOCO and FXCO (P = 0.002, P < 0.001), respectively. Correlation analysis demonstrated an inverse association between plasma OEA levels and percent body fat (r = -0.21, P = 0.04), and a positive association was observed between the plasma arachidonoyl ethanolamide (AEA)/OEA ratio and android:gynoid fat (r = 0.23, P = 0.02), respectively. Results suggest that plasma NAE levels are upregulated via their dietary lipid substrates and may modulate regional and total fat mass through lipid-signaling mechanisms. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

  13. Exploring Local Level Factors Shaping the Implementation of a Blended Learning Module for Information and Geospatial Literacy in Ontario

    Directory of Open Access Journals (Sweden)

    Michelle M. Vine

    2016-12-01

    Full Text Available The objectives of this research study were to examine local level factors shaping the implementation of a blended pedagogical approach for geospatial- and information-literacy, and to understand implementer satisfaction. As such, we addressed the following research questions: What local-level factors shape the implementation of the blended learning model? and How satisfied are implementers (faculty, administrators and library instructional/support staff with the new blended learning model for geospatial and information fluency? Focus groups (n=7 plus one interview (total n=22 were conducted with key stakeholders (e.g., staff, faculty, administrators to better understand facilitators, barriers, and/or issues related to module development, in addition to perceptions about how the modules are utilized by teaching assistants (TAs, instructional assistants (IAs, and instructors. Participants were identified according to their status as either discipline-specific instructional staff (i.e., instructor, TA, IA or staff who supported the development of modules (i.e., library instructional staff, library management, administrators. From an ontological standpoint that privileges an individual perspective on the nature of reality, while epistemologically seeking to understand the relationship between the “knower” and what can be known, we adopted a theory of constructivism to support this inquiry. Transcripts were imported into a qualitative analysis software package (NVivo 8.0 for organization, coding and analysis. Instructors found value in the online modules, particularly in a blended learning setting. Instructors felt that having the material in advance, in-class time could be better focused on interaction, assignments, and assessments and resulted in reduced anxiety in busy lab environments. Several key themes emerged, including: (a instructor expectations (time constraints, sustainability, and collaborative nature of development process and

  14. Working Memory Modulates Glutamate Levels in the Dorsolateral Prefrontal Cortex during 1H fMRS

    Directory of Open Access Journals (Sweden)

    Eric A. Woodcock

    2018-03-01

    Full Text Available Glutamate is involved in excitatory neurotransmission and metabolic processes related to brain function. Previous studies using proton functional magnetic resonance spectroscopy (1H fMRS have demonstrated elevated cortical glutamate levels by 2–4% during visual and motor stimulation, relative to periods of no stimulation. Here, we extended this approach to working memory cognitive task performance, which has been consistently associated with dorsolateral prefrontal cortex (dlPFC activation. Sixteen healthy adult volunteers completed a continuous visual fixation “rest” task followed by a letter 2-back working memory task during 1H fMRS acquisition of the left dlPFC, which encompassed Brodmann areas 45 and 46 over a 4.5-cm3 volume. Using a 100% automated fitting procedure integrated with LCModel, raw spectra were eddy current-, phase-, and shift-corrected prior to quantification resulting in a 32s temporal resolution or 8 averages per spectra. Task compliance was high (95 ± 11% correct and the mean Cramer-Rao Lower Bound of glutamate was 6.9 ± 0.9%. Relative to continuous passive visual fixation, left dlPFC glutamate levels were significantly higher by 2.7% (0.32 mmol/kg wet weight during letter 2-back performance. Elevated dlPFC glutamate levels reflect increased metabolic activity and excitatory neurotransmission driven by working memory-related cognitive demands. These results provide the first in vivo demonstration of elevated dlPFC glutamate levels during working memory.

  15. Level of processing modulates the neural correlates of emotional memory formation

    OpenAIRE

    Ritchey, Maureen; LaBar, Kevin S.; Cabeza, Roberto

    2010-01-01

    Emotion is known to influence multiple aspects of memory formation, including the initial encoding of the memory trace and its consolidation over time. However, the neural mechanisms whereby emotion impacts memory encoding remain largely unexplored. The present study employed a levels-of-processing manipulation to characterize the impact of emotion on encoding with and without the influence of elaborative processes. Participants viewed emotionally negative, neutral, and positive scenes under ...

  16. Implicit learning of predictable sound sequences modulates human brain responses at different levels of the auditory hierarchy

    Directory of Open Access Journals (Sweden)

    Françoise eLecaignard

    2015-09-01

    Full Text Available Deviant stimuli, violating regularities in a sensory environment, elicit the Mismatch Negativity (MMN, largely described in the Event-Related Potential literature. While it is widely accepted that the MMN reflects more than basic change detection, a comprehensive description of mental processes modulating this response is still lacking. Within the framework of predictive coding, deviance processing is part of an inference process where prediction errors (the mismatch between incoming sensations and predictions established through experience are minimized. In this view, the MMN is a measure of prediction error, which yields specific expectations regarding its modulations by various experimental factors. In particular, it predicts that the MMN should decrease as the occurrence of a deviance becomes more predictable. We conducted a passive oddball EEG study and manipulated the predictability of sound sequences by means of different temporal structures. Importantly, our design allows comparing mismatch responses elicited by predictable and unpredictable violations of a simple repetition rule and therefore departs from previous studies that investigate violations of different time-scale regularities. We observed a decrease of the MMN with predictability and interestingly, a similar effect at earlier latencies, within 70 ms after deviance onset. Following these pre-attentive responses, a reduced P3a was measured in the case of predictable deviants. We conclude that early and late deviance responses reflect prediction errors, triggering belief updating within the auditory hierarchy. Beside, in this passive study, such perceptual inference appears to be modulated by higher-level implicit learning of sequence statistical structures. Our findings argue for a hierarchical model of auditory processing where predictive coding enables implicit extraction of environmental regularities.

  17. Lactobacillus rhamnosus CNCMI-4317 Modulates Fiaf/Angptl4 in Intestinal Epithelial Cells and Circulating Level in Mice.

    Science.gov (United States)

    Jacouton, Elsa; Mach, Núria; Cadiou, Julie; Lapaque, Nicolas; Clément, Karine; Doré, Joël; van Hylckama Vlieg, Johan E T; Smokvina, Tamara; Blottière, Hervé M

    2015-01-01

    Identification of new targets for metabolic diseases treatment or prevention is required. In this context, FIAF/ANGPTL4 appears as a crucial regulator of energy homeostasis. Lactobacilli are often considered to display beneficial effect for their hosts, acting on different regulatory pathways. The aim of the present work was to study the effect of several lactobacilli strains on Fiaf gene expression in human intestinal epithelial cells (IECs) and on mice tissues to decipher the underlying mechanisms. Nineteen lactobacilli strains have been tested on HT-29 human intestinal epithelial cells for their ability to regulate Fiaf gene expression by RT-qPCR. In order to determine regulated pathways, we analysed the whole genome transcriptome of IECs. We then validated in vivo bacterial effects using C57BL/6 mono-colonized mice fed with normal chow. We identified one strain (Lactobacillus rhamnosus CNCMI-4317) that modulated Fiaf expression in IECs. This regulation relied potentially on bacterial surface-exposed molecules and seemed to be PPAR-γ independent but PPAR-α dependent. Transcriptome functional analysis revealed that multiple pathways including cellular function and maintenance, lymphoid tissue structure and development, as well as lipid metabolism were regulated by this strain. The regulation of immune system and lipid and carbohydrate metabolism was also confirmed by overrepresentation of Gene Ontology terms analysis. In vivo, circulating FIAF protein was increased by the strain but this phenomenon was not correlated with modulation Fiaf expression in tissues (except a trend in distal small intestine). We showed that Lactobacillus rhamnosus CNCMI-4317 induced Fiaf expression in human IECs, and increased circulating FIAF protein level in mice. Moreover, this effect was accompanied by transcriptome modulation of several pathways including immune response and metabolism in vitro.

  18. Msh2 acts in medium-spiny striatal neurons as an enhancer of CAG instability and mutant huntingtin phenotypes in Huntington's disease knock-in mice.

    Directory of Open Access Journals (Sweden)

    Marina Kovalenko

    Full Text Available The CAG trinucleotide repeat mutation in the Huntington's disease gene (HTT exhibits age-dependent tissue-specific expansion that correlates with disease onset in patients, implicating somatic expansion as a disease modifier and potential therapeutic target. Somatic HTT CAG expansion is critically dependent on proteins in the mismatch repair (MMR pathway. To gain further insight into mechanisms of somatic expansion and the relationship of somatic expansion to the disease process in selectively vulnerable MSNs we have crossed HTT CAG knock-in mice (HdhQ111 with mice carrying a conditional (floxed Msh2 allele and D9-Cre transgenic mice, in which Cre recombinase is expressed specifically in MSNs within the striatum. Deletion of Msh2 in MSNs eliminated Msh2 protein in those neurons. We demonstrate that MSN-specific deletion of Msh2 was sufficient to eliminate the vast majority of striatal HTT CAG expansions in HdhQ111 mice. Furthermore, MSN-specific deletion of Msh2 modified two mutant huntingtin phenotypes: the early nuclear localization of diffusely immunostaining mutant huntingtin was slowed; and the later development of intranuclear huntingtin inclusions was dramatically inhibited. Therefore, Msh2 acts within MSNs as a genetic enhancer both of somatic HTT CAG expansions and of HTT CAG-dependent phenotypes in mice. These data suggest that the selective vulnerability of MSNs may be at least in part contributed by the propensity for somatic expansion in these neurons, and imply that intervening in the expansion process is likely to have therapeutic benefit.

  19. Alcohol modulates circulating levels of interleukin-6 and monocyte chemoattractant protein-1 in chronic pancreatitis

    DEFF Research Database (Denmark)

    Pedersen, N; Larsen, S; Seidelin, J B

    2004-01-01

    Cytokines are markers of acute pancreatic inflammation and essential for distant organ injury, but they also stimulate pancreatic fibrogenesis and are thus involved in the progression from acute pancreatitis to chronic pancreatic injury and fibrosis. The aim of this study was to evaluate the circ...... the circulating levels of IL-6, MCP-1, TGF-beta1, IGF-1 and IGFBP-3 in patients with alcoholic chronic pancreatitis (CP).......Cytokines are markers of acute pancreatic inflammation and essential for distant organ injury, but they also stimulate pancreatic fibrogenesis and are thus involved in the progression from acute pancreatitis to chronic pancreatic injury and fibrosis. The aim of this study was to evaluate...

  20. The Pseudomonas aeruginosa Chp Chemosensory System Regulates Intracellular cAMP Levels by Modulating Adenylate Cyclase Activity

    Science.gov (United States)

    Fulcher, Nanette B.; Holliday, Phillip M.; Klem, Erich; Cann, Martin J.; Wolfgang, Matthew C.

    2010-01-01

    Summary Multiple virulence systems in the opportunistic pathogen Pseudomonas aeruginosa are regulated by the second messenger signaling molecule adenosine 3’, 5’-cyclic monophosphate (cAMP). Production of cAMP by the putative adenylate cyclase enzyme CyaB represents a critical control point for virulence gene regulation. To identify regulators of CyaB, we screened a transposon insertion library for mutants with reduced intracellular cAMP. The majority of insertions resulting in reduced cAMP mapped to the Chp gene cluster encoding a putative chemotaxis-like chemosensory system. Further genetic analysis of the Chp system revealed that it has both positive and negative effects on intracellular cAMP and that it regulates cAMP levels by modulating CyaB activity. The Chp system was previously implicated in the production and function of type IV pili (TFP). Given that cAMP and the cAMP-dependent transcriptional regulator Vfr control TFP biogenesis gene expression, we explored the relationship between cAMP, the Chp system and TFP regulation. We discovered that the Chp system controls TFP production through modulation of cAMP while control of TFP-dependent twitching motility is cAMP-independent. Overall, our data define a novel function for a chemotaxis-like system in controlling cAMP production and establish a regulatory link between the Chp system, TFP and other cAMP-dependent virulence systems. PMID:20345659

  1. Histone deacetylase inhibition decreases cholesterol levels in neuronal cells by modulating key genes in cholesterol synthesis, uptake and efflux.

    Directory of Open Access Journals (Sweden)

    Maria João Nunes

    Full Text Available Cholesterol is an essential component of the central nervous system and increasing evidence suggests an association between brain cholesterol metabolism dysfunction and the onset of neurodegenerative disorders. Interestingly, histone deacetylase inhibitors (HDACi such as trichostatin A (TSA are emerging as promising therapeutic approaches in neurodegenerative diseases, but their effect on brain cholesterol metabolism is poorly understood. We have previously demonstrated that HDACi up-regulate CYP46A1 gene transcription, a key enzyme in neuronal cholesterol homeostasis. In this study, TSA was shown to modulate the transcription of other genes involved in cholesterol metabolism in human neuroblastoma cells, namely by up-regulating genes that control cholesterol efflux and down-regulating genes involved in cholesterol synthesis and uptake, thus leading to an overall decrease in total cholesterol content. Furthermore, co-treatment with the amphipathic drug U18666A that can mimic the intracellular cholesterol accumulation observed in cells of Niemman-Pick type C patients, revealed that TSA can ameliorate the phenotype induced by pathological cholesterol accumulation, by restoring the expression of key genes involved in cholesterol synthesis, uptake and efflux and promoting lysosomal cholesterol redistribution. These results clarify the role of TSA in the modulation of neuronal cholesterol metabolism at the transcriptional level, and emphasize the idea of HDAC inhibition as a promising therapeutic tool in neurodegenerative disorders with impaired cholesterol metabolism.

  2. Saltmarsh boundary modulates dispersal of mangrove propagules: implications for mangrove migration with sea-level rise.

    Directory of Open Access Journals (Sweden)

    Jennifer M Peterson

    Full Text Available Few studies have empirically examined the suite of mechanisms that underlie the distributional shifts displayed by organisms in response to changing climatic condition. Mangrove forests are expected to move inland as sea-level rises, encroaching on saltmarsh plants inhabiting higher elevations. Mangrove propagules are transported by tidal waters and propagule dispersal is likely modified upon encountering the mangrove-saltmarsh ecotone, the implications of which are poorly known. Here, using an experimental approach, we record landward and seaward dispersal and subsequent establishment of mangrove propagules that encounter biotic boundaries composed of two types of saltmarsh taxa: succulents and grasses. Our findings revealed that propagules emplaced within saltmarsh vegetation immediately landward of the extant mangrove fringe boundary frequently dispersed in the seaward direction. However, propagules moved seaward less frequently and over shorter distances upon encountering boundaries composed of saltmarsh grasses versus succulents. We uniquely confirmed that the small subset of propagules dispersing landward displayed proportionately higher establishment success than those transported seaward. Although impacts of ecotones on plant dispersal have rarely been investigated in situ, our experimental results indicate that the interplay between tidal transport and physical attributes of saltmarsh vegetation influence boundary permeability to propagules, thereby directing the initial phase of shifting mangrove distributions. The incorporation of tidal inundation information and detailed data on landscape features, such as the structure of saltmarsh vegetation at mangrove boundaries, should improve the accuracy of models that are being developed to forecast mangrove distributional shifts in response to sea-level rise.

  3. Saltmarsh boundary modulates dispersal of mangrove propagules: implications for mangrove migration with sea-level rise.

    Science.gov (United States)

    Peterson, Jennifer M; Bell, Susan S

    2015-01-01

    Few studies have empirically examined the suite of mechanisms that underlie the distributional shifts displayed by organisms in response to changing climatic condition. Mangrove forests are expected to move inland as sea-level rises, encroaching on saltmarsh plants inhabiting higher elevations. Mangrove propagules are transported by tidal waters and propagule dispersal is likely modified upon encountering the mangrove-saltmarsh ecotone, the implications of which are poorly known. Here, using an experimental approach, we record landward and seaward dispersal and subsequent establishment of mangrove propagules that encounter biotic boundaries composed of two types of saltmarsh taxa: succulents and grasses. Our findings revealed that propagules emplaced within saltmarsh vegetation immediately landward of the extant mangrove fringe boundary frequently dispersed in the seaward direction. However, propagules moved seaward less frequently and over shorter distances upon encountering boundaries composed of saltmarsh grasses versus succulents. We uniquely confirmed that the small subset of propagules dispersing landward displayed proportionately higher establishment success than those transported seaward. Although impacts of ecotones on plant dispersal have rarely been investigated in situ, our experimental results indicate that the interplay between tidal transport and physical attributes of saltmarsh vegetation influence boundary permeability to propagules, thereby directing the initial phase of shifting mangrove distributions. The incorporation of tidal inundation information and detailed data on landscape features, such as the structure of saltmarsh vegetation at mangrove boundaries, should improve the accuracy of models that are being developed to forecast mangrove distributional shifts in response to sea-level rise.

  4. Modulation of cholesterol levels in broiler meat by dietary garlic and copper.

    Science.gov (United States)

    Konjufca, V H; Pesti, G M; Bakalli, R I

    1997-09-01

    Male Ross x Ross 208 chickens were fed from hatching to 21 d of age either a control diet (based on corn and soybean meal) or the control diet supplemented with 0, 1.5, 3.0, and 4.5% of a commercial garlic powder in Experiments 1 and 2. Once the dose-response relationship was established, 3% garlic powder or 63 or 180 mg/kg copper as cupric citrate or cupric sulfate pentahydrate were supplemented to the diet (Experiments 3, 4, 5, and 6). In the first two experiments, reductions of plasma cholesterol (P = 0.006) and triacylglycerols (P = 0.013) and liver (P = 0.012) and breast muscle (P = 0.165) cholesterol were observed in garlic-supplemented birds. Feeding either garlic powder or copper (63 and 180 mg/kg) resulted in reduced levels of plasma cholesterol, liver cholesterol, blood reduced glutathione, and breast and thigh muscle cholesterol. Differences were significant at P copper (P = 0.982). The activity of fatty acid synthetase was decreased in birds fed copper (P = 0.035). Both garlic and copper supplements decreased cholesterol 7 alpha-hydroxylase activity (P = 0.024 and P = 0.022, respectively). The results of these trials confirm the findings that garlic and copper alter lipid and cholesterol metabolism. However, they do not work by the same mechanism. Feeding dietary garlic or copper for 21 d reduced cholesterol levels of broiler meat without altering growth of the chickens or feed efficiency.

  5. Modulation of weight off-loading level over body-weight supported locomotion training.

    Science.gov (United States)

    Wang, Ping; Low, K H; Lim, Peter A C; McGregor, A H

    2011-01-01

    With the evolution of robotic systems to facilitate overground walking rehabilitation, it is important to understand the effect of robotic-aided body-weight supported loading on lower limb muscle activity, if we are to optimize neuromotor recovery. To achieve this objective, we have collected and studied electromyography (EMG) data from key muscles in the lower extremity from healthy subjects walking over a wide range of body-weight off-loading levels as provided by a bespoke gait robot. By examining the impact of body-weight off-loading, it was found that muscle activation patterns were sensitive to the level of off-loading. In addition, a large off-loading might introduce disturbance of muscle activation pattern, led to a wider range of motion in terms of dorsiflexion/plantarflexion. Therefore, any future overground training machine should be enhanced to exclude unnecessary effect of body off-loading in securing the sustaining upright posture and providing assist-as-needed BWS over gait rehabilitation. © 2011 IEEE

  6. Plasma Triglyceride Levels May Be Modulated by Gene Expression of IQCJ, NXPH1, PHF17 and MYB in Humans

    Directory of Open Access Journals (Sweden)

    Bastien Vallée Marcotte

    2017-01-01

    Full Text Available A genome-wide association study (GWAS by our group identified loci associated with the plasma triglyceride (TG response to ω-3 fatty acid (FA supplementation in IQCJ, NXPH1, PHF17 and MYB. Our aim is to investigate potential mechanisms underlying the associations between single nucleotide polymorphisms (SNPs in the four genes and TG levels following ω-3 FA supplementation. 208 subjects received 3 g/day of ω-3 FA (1.9–2.2 g of EPA and 1.1 g of docosahexaenoic acid (DHA for six weeks. Plasma TG were measured before and after the intervention. 67 SNPs were selected to increase the density of markers near GWAS hits. Genome-wide expression and methylation analyses were conducted on respectively 30 and 35 participants’ blood sample together with in silico analyses. Two SNPs of IQCJ showed different affinities to splice sites depending on alleles. Expression levels were influenced by genotype for one SNP in NXPH1 and one in MYB. Associations between 12 tagged SNPs of IQCJ, 26 of NXPH1, seven of PHF17 and four of MYB and gene-specific CpG site methylation levels were found. The response of plasma TG to ω-3 FA supplementation may be modulated by the effect of DNA methylation on expression levels of genes revealed by GWAS.

  7. High level of oxygen treatment causes cardiotoxicity with arrhythmias and redox modulation

    Energy Technology Data Exchange (ETDEWEB)

    Chapalamadugu, Kalyan C.; Panguluri, Siva K. [Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL (United States); Bennett, Eric S. [Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL (United States); Kolliputi, Narasaiah [Division of Allergy and Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL (United States); Tipparaju, Srinivas M., E-mail: stippara@health.usf.edu [Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL (United States)

    2015-01-01

    Hyperoxia exposure in mice leads to cardiac hypertrophy and voltage-gated potassium (Kv) channel remodeling. Because redox balance of pyridine nucleotides affects Kv function and hyperoxia alters cellular redox potential, we hypothesized that hyperoxia exposure leads to cardiac ion channel disturbances and redox changes resulting in arrhythmias. In the present study, we investigated the electrical changes and redox abnormalities caused by 72 h hyperoxia treatment in mice. Cardiac repolarization changes were assessed by acquiring electrocardiogram (ECG) and cardiac action potentials (AP). Biochemical assays were employed to identify the pyridine nucleotide changes, Kv1.5 expression and myocardial injury. Hyperoxia treatment caused marked bradycardia, arrhythmia and significantly prolonged (ms) the, RR (186.2 ± 10.7 vs. 146.4 ± 6.2), PR (46.8 ± 3.1 vs. 39.3 ± 1.6), QRS (10.8 ± 0.6 vs. 8.5 ± 0.2), QTc (57.1 ± 3.5 vs. 40 ± 1.4) and JT (13.4 ± 2.1 vs. 7.0 ± 0.5) intervals, when compared with normoxia group. Hyperoxia treatment also induced significant increase in cardiac action potential duration (APD) (ex-APD{sub 90}; 73.8 ± 9.5 vs. 50.9 ± 3.1 ms) and elevated levels of serum markers of myocardial injury; cardiac troponin I (TnI) and lactate dehydrogenase (LDH). Hyperoxia exposure altered cardiac levels of mRNA/protein expression of; Kv1.5, Kvβ subunits and SiRT1, and increased ratios of reduced pyridine nucleotides (NADH/NAD and NADPH/NADP). Inhibition of SiRT1 in H9C2 cells using Splitomicin resulted in decreased SiRT1 and Kv1.5 expression, suggesting that SiRT1 may mediate Kv1.5 downregulation. In conclusion, the cardiotoxic effects of hyperoxia exposure involve ion channel disturbances and redox changes resulting in arrhythmias. - Highlights: • Hyperoxia treatment leads to arrhythmia with prolonged QTc and action potential duration. • Hyperoxia treatment alters cardiac pyridine nucleotide [NAD(P)H/NAD(P)] levels. • SiRT1 and Kv1.5 are co

  8. High level of oxygen treatment causes cardiotoxicity with arrhythmias and redox modulation

    International Nuclear Information System (INIS)

    Chapalamadugu, Kalyan C.; Panguluri, Siva K.; Bennett, Eric S.; Kolliputi, Narasaiah; Tipparaju, Srinivas M.

    2015-01-01

    Hyperoxia exposure in mice leads to cardiac hypertrophy and voltage-gated potassium (Kv) channel remodeling. Because redox balance of pyridine nucleotides affects Kv function and hyperoxia alters cellular redox potential, we hypothesized that hyperoxia exposure leads to cardiac ion channel disturbances and redox changes resulting in arrhythmias. In the present study, we investigated the electrical changes and redox abnormalities caused by 72 h hyperoxia treatment in mice. Cardiac repolarization changes were assessed by acquiring electrocardiogram (ECG) and cardiac action potentials (AP). Biochemical assays were employed to identify the pyridine nucleotide changes, Kv1.5 expression and myocardial injury. Hyperoxia treatment caused marked bradycardia, arrhythmia and significantly prolonged (ms) the, RR (186.2 ± 10.7 vs. 146.4 ± 6.2), PR (46.8 ± 3.1 vs. 39.3 ± 1.6), QRS (10.8 ± 0.6 vs. 8.5 ± 0.2), QTc (57.1 ± 3.5 vs. 40 ± 1.4) and JT (13.4 ± 2.1 vs. 7.0 ± 0.5) intervals, when compared with normoxia group. Hyperoxia treatment also induced significant increase in cardiac action potential duration (APD) (ex-APD 90 ; 73.8 ± 9.5 vs. 50.9 ± 3.1 ms) and elevated levels of serum markers of myocardial injury; cardiac troponin I (TnI) and lactate dehydrogenase (LDH). Hyperoxia exposure altered cardiac levels of mRNA/protein expression of; Kv1.5, Kvβ subunits and SiRT1, and increased ratios of reduced pyridine nucleotides (NADH/NAD and NADPH/NADP). Inhibition of SiRT1 in H9C2 cells using Splitomicin resulted in decreased SiRT1 and Kv1.5 expression, suggesting that SiRT1 may mediate Kv1.5 downregulation. In conclusion, the cardiotoxic effects of hyperoxia exposure involve ion channel disturbances and redox changes resulting in arrhythmias. - Highlights: • Hyperoxia treatment leads to arrhythmia with prolonged QTc and action potential duration. • Hyperoxia treatment alters cardiac pyridine nucleotide [NAD(P)H/NAD(P)] levels. • SiRT1 and Kv1.5 are co-regulated in

  9. Alcohol modulates circulating levels of interleukin-6 and monocyte chemoattractant protein-1 in chronic pancreatitis

    DEFF Research Database (Denmark)

    Pedersen, N; Larsen, S; Seidelin, J B

    2004-01-01

    was to evaluate the circulating levels of IL-6, MCP-1, TGF-beta1, IGF-1 and IGFBP-3 in patients with alcoholic chronic pancreatitis (CP). METHODS: Twelve male patients with severe CP and 11 matched controls ingested 40 g alcohol. Plasma cytokine concentrations were measured for 24 h and assessed by sandwich ELISA......BACKGROUND: Cytokines are markers of acute pancreatic inflammation and essential for distant organ injury, but they also stimulate pancreatic fibrogenesis and are thus involved in the progression from acute pancreatitis to chronic pancreatic injury and fibrosis. The aim of this study...... techniques. RESULTS: IL-6 was higher in CP at fasting and 1, 4 and 24 h after alcohol intake (P

  10. CD36 Modulates Fasting and Preabsorptive Hormone and Bile Acid Levels.

    Science.gov (United States)

    Shibao, Cyndya A; Celedonio, Jorge E; Tamboli, Robyn; Sidani, Reem; Love-Gregory, Latisha; Pietka, Terri; Xiong, Yanhua; Wei, Yan; Abumrad, Naji N; Abumrad, Nada A; Flynn, Charles Robb

    2018-05-01

    Abnormal fatty acid (FA) metabolism contributes to diabetes and cardiovascular disease. The FA receptor CD36 has been linked to risk of metabolic syndrome. In rodents CD36 regulates various aspects of fat metabolism, but whether it has similar actions in humans is unknown. We examined the impact of a coding single-nucleotide polymorphism in CD36 on postprandial hormone and bile acid (BA) responses. To examine whether the minor allele (G) of coding CD36 variant rs3211938 (G/T), which reduces CD36 level by ∼50%, influences hormonal responses to a high-fat meal (HFM). Obese African American (AA) women carriers of the G allele of rs3211938 (G/T) and weight-matched noncarriers (T/T) were studied before and after a HFM. Two-center study. Obese AA women. HFM. Early preabsorptive responses (10 minutes) and extended excursions in plasma hormones [C-peptide, insulin, incretins, ghrelin fibroblast growth factor (FGF)19, FGF21], BAs, and serum lipoproteins (chylomicrons, very-low-density lipoprotein) were determined. At fasting, G-allele carriers had significantly reduced cholesterol and glycodeoxycholic acid and consistent but nonsignificant reductions of serum lipoproteins. Levels of GLP-1 and pancreatic polypeptide (PP) were reduced 60% to 70% and those of total BAs were 1.8-fold higher. After the meal, G-allele carriers displayed attenuated early (-10 to 10 minute) responses in insulin, C-peptide, GLP-1, gastric inhibitory peptide, and PP. BAs exhibited divergent trends in G allele carriers vs noncarriers concomitant with differential FGF19 responses. CD36 plays an important role in the preabsorptive hormone and BA responses that coordinate brain and gut regulation of energy metabolism.

  11. THYROID HORMONE TREATED ASTROCYTES INDUCE MATURATION OF CEREBRAL CORTICAL NEURONS THROUGH MODULATION OF PROTEOGLYCAN LEVELS

    Directory of Open Access Journals (Sweden)

    Romulo Sperduto Dezonne

    2013-08-01

    Full Text Available Proper brain neuronal circuitry formation and synapse development is dependent on specific cues, either genetic or epigenetic, provided by the surrounding neural environment. Within these signals, thyroid hormones (T3 and T4 play crucial role in several steps of brain morphogenesis including proliferation of progenitor cells, neuronal differentiation, maturation, migration, and synapse formation. The lack of thyroid hormones during childhood is associated with several impair neuronal connections, cognitive deficits, and mental disorders. Many of the thyroid hormones effects are mediated by astrocytes, although the mechanisms underlying these events are still unknown. In this work, we investigated the effect of 3, 5, 3’-triiodothyronine-treated (T3-treated astrocytes on cerebral cortex neuronal differentiation. Culture of neural progenitors from embryonic cerebral cortex mice onto T3-treated astrocyte monolayers yielded an increment in neuronal population, followed by enhancement of neuronal maturation, arborization and neurite outgrowth. In addition, real time PCR assays revealed an increase in the levels of the heparan sulfate proteoglycans, Glypican 1 (GPC-1 and Syndecans 3 e 4 (SDC-3 e SDC-4, followed by a decrease in the levels of the chondroitin sulfate proteoglycan, Versican. Disruption of glycosaminoglycan chains by chondroitinase AC or heparanase III completely abolished the effects of T3-treated astrocytes on neuronal morphogenesis. Our work provides evidence that astrocytes are key mediators of T3 actions on cerebral cortex neuronal development and identified potential molecules and pathways involved in neurite extension; which might eventually contribute to a better understanding of axonal regeneration, synapse formation and neuronal circuitry recover.

  12. A Fast-Processing Modulation Strategy for Three-Phase Four-Leg Neutral-Point-Clamped Inverter Based on the Circuit-Level Decoupling Concept

    DEFF Research Database (Denmark)

    Ghoreishy, Hoda; Zhang, Zhe; Thomsen, Ole Cornelius

    2012-01-01

    In this paper, a modulation strategy based on the circuit-level decoupling concept is proposed and investigated for the three-level four-leg neutral-point-clamped (NPC) inverter,with the aim of delivering power to all sorts of loads, linear/nonlinear and balanced/unbalanced. By applying the propo......In this paper, a modulation strategy based on the circuit-level decoupling concept is proposed and investigated for the three-level four-leg neutral-point-clamped (NPC) inverter,with the aim of delivering power to all sorts of loads, linear/nonlinear and balanced/unbalanced. By applying...... the proposed modulation strategy, the four-leg NPC inverter can be decoupled into three three-level Buck converters in each defined operating section. This makes the controller design much simpler compared to the conventional four-leg NPC inverter controllers. Also, this technique can be implemented...

  13. A mixed signal multi-chip module with high speed serial output links for the ATLAS Level-1 trigger

    CERN Document Server

    Pfeiffer, U

    2000-01-01

    We have built and tested a mixed signal multi-chip module (MCM) to be used in the Level-1 Pre-Processor system for the Calorimeter Trigger of the ATLAS experiment at CERN. The MCM performs high speed digital signal processing on four analogue input signals. Results are transmitted serially at a serial data rate of 800 MBd. Nine chips of different technologies are mounted on a four layer Cu substrate. ADC converters and serialiser chips are the major consumers of electrical power on the MCM, which amounts to 9 W for all dies. Special cut-out areas are used to dissipate heat directly to the copper substrate. In this paper we report on design criteria, chosen MCM technology for substrate and die mounting, experiences with the MCM operation and measurement results. (4 refs).

  14. Brain Aromatase Modulates Serotonergic Neuron by Regulating Serotonin Levels in Zebrafish Embryos and Larvae

    Directory of Open Access Journals (Sweden)

    Zulvikar Syambani Ulhaq

    2018-05-01

    Full Text Available Teleost fish are known to express two isoforms of P450 aromatase, a key enzyme for estrogen synthesis. One of the isoforms, brain aromatase (AroB, cyp19a1b, is highly expressed during early development of zebrafish, thereby suggesting its role in brain development. On the other hand, early development of serotonergic neuron, one of the major monoamine neurons, is considered to play an important role in neurogenesis. Therefore, in this study, we investigated the role of AroB in development of serotonergic neuron by testing the effects of (1 estradiol (E2 exposure and (2 morpholino (MO-mediated AroB knockdown. When embryos were exposed to E2, the effects were biphasic. The low dose of E2 (0.005 µM significantly increased serotonin (5-HT positive area at 48 hour post-fertilization (hpf detected by immunohistochemistry and relative mRNA levels of tryptophan hydroxylase isoforms (tph1a, tph1b, and tph2 at 96 hpf measured by semi-quantitative PCR. To test the effects on serotonin transmission, heart rate and thigmotaxis, an indicator of anxiety, were analyzed. The low dose also significantly increased heart rate at 48 hpf and decreased thigmotaxis. The high dose of E2 (1 µM exhibited opposite effects in all parameters. The effects of both low and high doses were reversed by addition of estrogen receptor (ER blocker, ICI 182,780, thereby suggesting that the effects were mediated through ER. When AroB MO was injected to fertilized eggs, 5-HT-positive area was significantly decreased, while the significant decrease in relative tph mRNA levels was found only with tph2 but not with two other isoforms. AroB MO also decreased heart rate and increased thigmotaxis. All the effects were rescued by co-injection with AroB mRNA and by exposure to E2. Taken together, this study demonstrates the role of brain aromatase in development of serotonergic neuron in zebrafish embryos and larvae, implying that brain-formed estrogen is an important factor to

  15. Levels of the E2 interacting protein TopBP1 modulate papillomavirus maintenance stage replication

    Energy Technology Data Exchange (ETDEWEB)

    Kanginakudru, Sriramana, E-mail: skangina@iu.edu [Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN (United States); DeSmet, Marsha, E-mail: mdesmet@iupui.edu [Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN (United States); Thomas, Yanique, E-mail: ysthomas@umail.iu.edu [Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN (United States); Morgan, Iain M., E-mail: immorgan@vcu.edu [VCU Philips Institute for Oral Health Research, Virginia Commonwealth University, Richmond, Virginia (United States); Androphy, Elliot J., E-mail: eandro@iu.edu [Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN (United States); Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN (United States)

    2015-04-15

    The evolutionarily conserved DNA topoisomerase II beta-binding protein 1 (TopBP1) functions in DNA replication, DNA damage response, and cell survival. We analyzed the role of TopBP1 in human and bovine papillomavirus genome replication. Consistent with prior reports, TopBP1 co-localized in discrete nuclear foci and was in complex with papillomavirus E2 protein. Similar to E2, TopBP1 is recruited to the region of the viral origin of replication during G1/S and early S phase. TopBP1 knockdown increased, while over-expression decreased transient virus replication, without affecting cell cycle. Similarly, using cell lines harboring HPV-16 or HPV-31 genome, TopBP1 knockdown increased while over-expression reduced viral copy number relative to genomic DNA. We propose a model in which TopBP1 serves dual roles in viral replication: it is essential for initiation of replication yet it restricts viral copy number. - Highlights: • Protein interaction study confirmed In-situ interaction between TopBP1 and E2. • TopBP1 present at papillomavirus ori in G1/S and early S phase of cell cycle. • TopBP1 knockdown increased, over-expression reduced virus replication. • TopBP1 protein level change did not influence cell survival or cell cycle. • TopBP1 displaced from papillomavirus ori after initiation of replication.

  16. Transcription-Replication Conflict Orientation Modulates R-Loop Levels and Activates Distinct DNA Damage Responses.

    Science.gov (United States)

    Hamperl, Stephan; Bocek, Michael J; Saldivar, Joshua C; Swigut, Tomek; Cimprich, Karlene A

    2017-08-10

    Conflicts between transcription and replication are a potent source of DNA damage. Co-transcriptional R-loops could aggravate such conflicts by creating an additional barrier to replication fork progression. Here, we use a defined episomal system to investigate how conflict orientation and R-loop formation influence genome stability in human cells. R-loops, but not normal transcription complexes, induce DNA breaks and orientation-specific DNA damage responses during conflicts with replication forks. Unexpectedly, the replisome acts as an orientation-dependent regulator of R-loop levels, reducing R-loops in the co-directional (CD) orientation but promoting their formation in the head-on (HO) orientation. Replication stress and deregulated origin firing increase the number of HO collisions leading to genome-destabilizing R-loops. Our findings connect DNA replication to R-loop homeostasis and suggest a mechanistic basis for genome instability resulting from deregulated DNA replication, observed in cancer and other disease states. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Levels of the E2 interacting protein TopBP1 modulate papillomavirus maintenance stage replication

    International Nuclear Information System (INIS)

    Kanginakudru, Sriramana; DeSmet, Marsha; Thomas, Yanique; Morgan, Iain M.; Androphy, Elliot J.

    2015-01-01

    The evolutionarily conserved DNA topoisomerase II beta-binding protein 1 (TopBP1) functions in DNA replication, DNA damage response, and cell survival. We analyzed the role of TopBP1 in human and bovine papillomavirus genome replication. Consistent with prior reports, TopBP1 co-localized in discrete nuclear foci and was in complex with papillomavirus E2 protein. Similar to E2, TopBP1 is recruited to the region of the viral origin of replication during G1/S and early S phase. TopBP1 knockdown increased, while over-expression decreased transient virus replication, without affecting cell cycle. Similarly, using cell lines harboring HPV-16 or HPV-31 genome, TopBP1 knockdown increased while over-expression reduced viral copy number relative to genomic DNA. We propose a model in which TopBP1 serves dual roles in viral replication: it is essential for initiation of replication yet it restricts viral copy number. - Highlights: • Protein interaction study confirmed In-situ interaction between TopBP1 and E2. • TopBP1 present at papillomavirus ori in G1/S and early S phase of cell cycle. • TopBP1 knockdown increased, over-expression reduced virus replication. • TopBP1 protein level change did not influence cell survival or cell cycle. • TopBP1 displaced from papillomavirus ori after initiation of replication

  18. Gene and process level modulation to overcome the bottlenecks of recombinant proteins expression in Pichia pastoris.

    Science.gov (United States)

    Prabhu, Ashish A; Boro, Bibari; Bharali, Biju; Chakraborty, Shuchishloka; Dasu, V Venkata

    2018-03-28

    Process development involving system metabolic engineering and bioprocess engineering has become one of the major thrust for the development of therapeutic proteins or enzymes. Pichia pastoris has emerged as a prominent host for the production of therapeutic protein or enzymes. Despite of producing high protein titers, various cellular and process level bottlenecks hinders the expression of recombinant proteins in P. pastoris. In the present review, we have summarized the recent developments in the expression of foreign proteins in P. pastoris. Further, we have discussed various cellular engineering strategies which include codon optimization, pathway engineering, signal peptide processing, development of protease deficient strain and glyco-engineered strains for the high yield protein secretion of recombinant protein. Bioprocess development of recombinant proteins in large scale bioreactor including medium optimization, optimum feeding strategy and co-substrate feeding in fed batch as well as continuous cultivation have been described. The recent advances in system and synthetic biology studies including metabolic flux analysis in understanding the phenotypic characteristics of recombinant Pichia and genome editing with CRISPR-CAS system have also been summarized. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Frequency-specific modulation of population-level frequency tuning in human auditory cortex

    Directory of Open Access Journals (Sweden)

    Roberts Larry E

    2009-01-01

    Full Text Available Abstract Background Under natural circumstances, attention plays an important role in extracting relevant auditory signals from simultaneously present, irrelevant noises. Excitatory and inhibitory neural activity, enhanced by attentional processes, seems to sharpen frequency tuning, contributing to improved auditory performance especially in noisy environments. In the present study, we investigated auditory magnetic fields in humans that were evoked by pure tones embedded in band-eliminated noises during two different stimulus sequencing conditions (constant vs. random under auditory focused attention by means of magnetoencephalography (MEG. Results In total, we used identical auditory stimuli between conditions, but presented them in a different order, thereby manipulating the neural processing and the auditory performance of the listeners. Constant stimulus sequencing blocks were characterized by the simultaneous presentation of pure tones of identical frequency with band-eliminated noises, whereas random sequencing blocks were characterized by the simultaneous presentation of pure tones of random frequencies and band-eliminated noises. We demonstrated that auditory evoked neural responses were larger in the constant sequencing compared to the random sequencing condition, particularly when the simultaneously presented noises contained narrow stop-bands. Conclusion The present study confirmed that population-level frequency tuning in human auditory cortex can be sharpened in a frequency-specific manner. This frequency-specific sharpening may contribute to improved auditory performance during detection and processing of relevant sound inputs characterized by specific frequency distributions in noisy environments.

  20. Parametric resonances in the amplitude-modulated probe-field absorption spectrum of a two-level atom driven by a resonance amplitude- and phase-modulated pumping field

    International Nuclear Information System (INIS)

    Sushilov, N.V.; Kholodkevich, E.D.

    1995-01-01

    An analytical expression is derived for the polarization induced by a weak probe field with periodically modulated amplitude in a two-level medium saturated by a strong amplitude-and phase-modulated resonance field. It is shown that the absorption spectrum of the probe field includes parametric resonances, the maxima corresponding to the condition δ= 2nΓ-Ω w and the minima to that of δ= (2n + 1)Γ- w , where δ is the probe-field detuning front the resonance frequency, Ω w is the modulation frequency of the probe-field amplitude, and Γ is the transition line width, n = 1, 2, 3, hor-ellipsis. At the specific modulation parameters, a substantial region of negative values (i.e., the region of amplification without the population inversion) exists in the absorption spectrum of the probe field

  1. Modulation in vitro and in vivo of cytotoxicity but not cellular levels of doxorubicin by the calmodulin inhibitor trifluoperazine is dependent on the level of resistance.

    Science.gov (United States)

    Ganapathi, R.; Schmidt, H.; Grabowski, D.; Melia, M.; Ratliff, N.

    1988-01-01

    The role of the calmodulin inhibitor trifluoperazine (TFP) in modulating the cellular levels and cytotoxicity in vitro and antitumour effects in vivo of doxorubicin (DOX), was evaluated in progressively DOX-resistant (5- to 40-fold) sublines of B16-BL6 mouse melanoma. In parental-sensitive B16-BL6 cells treated for 3 h, the IC50 of DOX was 0.1 microgram ml-1, and a less than 2-fold enhancement in DOX cell kill in the presence of a noncytotoxic concentration of 5 microM TFP was observed. However, in the DOX-resistant sublines, the IC50 was 0.7 to 5.0 micrograms ml-1 DOX in the absence of 5 microM TFP and 0.3 to 0.7 microgram ml-1 DOX in the presence of 5 microM TFP. The 2- to 7.5-fold decrease in the IC50 of DOX in the presence of 5 microM TFP, was dependent on the level of DOX-resistance in the various sublines. Compared to parental-sensitive cells, a 2-fold decrease in DOX-accumulation was evident only in the 40-fold DOX-resistant subline. Further, maximal enhancement (50%) of cellular DOX accumulation in the presence of 5 microM TFP was observed only in the 40-fold resistant cells treated with 5.0 micrograms ml-1 DOX. Retention of DOX in the 40-fold resistant subline was only 20% lower than similarly treated sensitive cells, and the inclusion of TFP increased DOX retention less than 10-15%. Antitumour studies in mice with experimental pulmonary metastases revealed that although DOX and DOX plus TFP had similar antitumour activity with the parental sensitive B16-BL6 cells, the combination of DOX plus TFP was significantly more effective than DOX alone with the DOX-resistant sublines. No overt toxicity was observed in normal mice treated with doses of TFP, DOX or DOX plus TFP used for in vivo chemotherapy studies. Results from this study suggest that gross cellular DOX levels do not appear to correlate with the magnitude of resistance, and the effects of TFP in modulating DOX resistance is possibly due to mechanisms other than mere alterations in cellular drug

  2. Creatures of habit (and control: a multi-level learning perspective on the modulation of congruency effects

    Directory of Open Access Journals (Sweden)

    Tobias eEgner

    2014-11-01

    Full Text Available The congruency sequence effect (CSE describes the finding that congruency effects in classic probes of selective attention (like the Stroop, Simon, and flanker tasks are smaller following an incongruent than following a congruent trial. The past two decades have generated a large literature on determinants and boundary conditions for the CSE and similar, congruency-proportion based modulations of congruency effects. A prolonged and heated theoretical discussion has been guided primarily by a historically motivated dichotomy between top-down control versus associative bottom-up explanations for these effects. In the present article, I attempt to integrate and contextualize the major empirical findings in this field by arguing that CSEs (and related effects are best understood as reflecting a composite of multiple levels of learning that differ in their level of abstraction. Specifically, learning does not only involve the trial-by-trial encoding, binding, and cued retrieval of specific stimulus-response associations, but also of more abstract trial features, including the spatial and temporal context in which a stimulus occurs, as well as internal states, like the experience of difficulty, and the attentional control settings that were employed in dealing with the stimulus. From this perspective, top-down control and bottom-up priming processes work in concert rather than in opposition. They represent different levels of abstraction in the same learning scheme and they serve a single, common goal: forming memory ensembles that will facilitate fast and appropriate responding to recurring stimuli or events in the environment.

  3. Hormonal modulation of food intake in response to low leptin levels induced by hypergravity

    Science.gov (United States)

    Moran, M. M.; Stein, T. P.; Wade, C. E.

    2001-01-01

    A loss in fat mass is a common response to centrifugation and it results in low circulating leptin concentrations. However, rats adapted to hypergravity are euphagic. The focus of this study was to examine leptin and other peripheral signals of energy balance in the presence of a hypergravity-induced loss of fat mass and euphagia. Male Sprague-Dawley rats were centrifuged for 14 days at gravity levels of 1.25, 1.5, or 2 G, or they remained stationary at 1 G. Urinary catecholamines, urinary corticosterone, food intake, and body mass were measured on Days 11 to 14. Plasma hormones and epididymal fat pad mass were measured on Day 14. Mean body mass of the 1.25, 1.5, and 2 G groups were significantly (P < 0.05) lower than controls, and no differences were found in food intake (g/day/100 g body mass) between the hypergravity groups and controls. Epididymal fat mass was 14%, 14%, and 21% lower than controls in the 1.25, 1.5, and 2.0 G groups, respectively. Plasma leptin was significantly reduced from controls by 46%, 45%, and 65% in the 1.25, 1.5, and 2 G groups, respectively. Plasma insulin was significantly lower in the 1.25, 1.5, and 2.0 G groups than controls by 35%, 38%, and 33%. No differences were found between controls and hypergravity groups in urinary corticosterone. Mean urinary epinephrine was significantly higher in the 1.5 and 2.0 G groups than in controls. Mean urinary norepinephrine was significantly higher in the 1.25, 1.5 and 2.0 G groups than in controls. Significant correlations were found between G load and body mass, fat mass, leptin, urinary epinephrine, and norepinephrine. During hypergravity exposure, maintenance of food intake is the result of a complex relationship between multiple pathways, which abates the importance of leptin as a primary signal.

  4. Modulation of the human gut microbiota by dietary fibres occurs at the species level.

    Science.gov (United States)

    Chung, Wing Sun Faith; Walker, Alan W; Louis, Petra; Parkhill, Julian; Vermeiren, Joan; Bosscher, Douwina; Duncan, Sylvia H; Flint, Harry J

    2016-01-11

    Dietary intake of specific non-digestible carbohydrates (including prebiotics) is increasingly seen as a highly effective approach for manipulating the composition and activities of the human gut microbiota to benefit health. Nevertheless, surprisingly little is known about the global response of the microbial community to particular carbohydrates. Recent in vivo dietary studies have demonstrated that the species composition of the human faecal microbiota is influenced by dietary intake. There is now potential to gain insights into the mechanisms involved by using in vitro systems that produce highly controlled conditions of pH and substrate supply. We supplied two alternative non-digestible polysaccharides as energy sources to three different human gut microbial communities in anaerobic, pH-controlled continuous-flow fermentors. Community analysis showed that supply of apple pectin or inulin resulted in the highly specific enrichment of particular bacterial operational taxonomic units (OTUs; based on 16S rRNA gene sequences). Of the eight most abundant Bacteroides OTUs detected, two were promoted specifically by inulin and six by pectin. Among the Firmicutes, Eubacterium eligens in particular was strongly promoted by pectin, while several species were stimulated by inulin. Responses were influenced by pH, which was stepped up, and down, between 5.5, 6.0, 6.4 and 6.9 in parallel vessels within each experiment. In particular, several experiments involving downshifts to pH 5.5 resulted in Faecalibacterium prausnitzii replacing Bacteroides spp. as the dominant sequences observed. Community diversity was greater in the pectin-fed than in the inulin-fed fermentors, presumably reflecting the differing complexity of the two substrates. We have shown that particular non-digestible dietary carbohydrates have enormous potential for modifying the gut microbiota, but these modifications occur at the level of individual strains and species and are not easily predicted a priori

  5. Systematic analysis of fly models with multiple drivers reveals different effects of ataxin-1 and huntingtin in neuron subtype-specific expression.

    Directory of Open Access Journals (Sweden)

    Risa Shiraishi

    Full Text Available The fruit fly, Drosophila melanogaster, is a commonly used model organism for neurodegenerative diseases. Its major advantages include a short lifespan and its susceptibility to manipulation using sophisticated genetic techniques. Here, we report the systematic comparison of fly models of two polyglutamine (polyQ diseases. We induced expression of the normal and mutant forms of full-length Ataxin-1 and Huntingtin exon 1 in cholinergic, dopaminergic, and motor neurons, and glial cells using cell type-specific drivers. We systematically analyzed their effects based on multiple phenotypes: eclosion rate, lifespan, motor performance, and circadian rhythms of spontaneous activity. This systematic assay system enabled us to quantitatively evaluate and compare the functional disabilities of different genotypes. The results suggest different effects of Ataxin-1 and Huntingtin on specific types of neural cells during development and in adulthood. In addition, we confirmed the therapeutic effects of LiCl and butyrate using representative models. These results support the usefulness of this assay system for screening candidate chemical compounds that modify the pathologies of polyQ diseases.

  6. Ser46 phosphorylation and prolyl-isomerase Pin1-mediated isomerization of p53 are key events in p53-dependent apoptosis induced by mutant huntingtin.

    Science.gov (United States)

    Grison, Alice; Mantovani, Fiamma; Comel, Anna; Agostoni, Elena; Gustincich, Stefano; Persichetti, Francesca; Del Sal, Giannino

    2011-11-01

    Huntington disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in the gene coding for huntingtin protein. Several mechanisms have been proposed by which mutant huntingtin (mHtt) may trigger striatal neurodegeneration, including mitochondrial dysfunction, oxidative stress, and apoptosis. Furthermore, mHtt induces DNA damage and activates a stress response. In this context, p53 plays a crucial role in mediating mHtt toxic effects. Here we have dissected the pathway of p53 activation by mHtt in human neuronal cells and in HD mice, with the aim of highlighting critical nodes that may be pharmacologically manipulated for therapeutic intervention. We demonstrate that expression of mHtt causes increased phosphorylation of p53 on Ser46, leading to its interaction with phosphorylation-dependent prolyl isomerase Pin1 and consequent dissociation from the apoptosis inhibitor iASPP, thereby inducing the expression of apoptotic target genes. Inhibition of Ser46 phosphorylation by targeting homeodomain-interacting protein kinase 2 (HIPK2), PKCδ, or ataxia telangiectasia mutated kinase, as well as inhibition of the prolyl isomerase Pin1, prevents mHtt-dependent apoptosis of neuronal cells. These results provide a rationale for the use of small-molecule inhibitors of stress-responsive protein kinases and Pin1 as a potential therapeutic strategy for HD treatment.

  7. Neuroactive steroids modulate HPA axis activity and cerebral brain-derived neurotrophic factor (BDNF) protein levels in adult male rats.

    Science.gov (United States)

    Naert, Gaëlle; Maurice, Tangui; Tapia-Arancibia, Lucia; Givalois, Laurent

    2007-01-01

    Depression is characterized by hypothalamo-pituitary-adrenocortical (HPA) axis hyperactivity. In this major mood disorder, neurosteroids and neurotrophins, particularly brain-derived neurotrophic factor (BDNF), seem to be implicated and have some antidepressant effects. BDNF is highly involved in regulation of the HPA axis, whereas neurosteroids effects have never been clearly established. In this systematic in vivo study, we showed that the principal neuroactive steroids, namely dehydroepiandrosterone (DHEA), pregnenolone (PREG) and their sulfate esters (DHEA-S and PREG-S), along with allopregnanolone (ALLO), stimulated HPA axis activity, while also modulating central BDNF contents. In detail, DHEA, DHEA-S, PREG, PREG-S and ALLO induced corticotropin-releasing hormone (CRH) and/or arginine vasopressin (AVP) synthesis and release at the hypothalamic level, thus enhancing plasma adrenocorticotropin hormone (ACTH) and corticosterone (CORT) concentrations. This stimulation of the HPA axis occurred concomitantly with BDNF modifications at the hippocampus, amygdala and hypothalamus levels. We showed that these neurosteroids induced rapid effects, probably via neurotransmitter receptors and delayed effects perhaps after metabolization in other neuroactive steroids. We highlighted that they had peripheral effects directly at the adrenal level by inducing CORT release, certainly after estrogenic metabolization. In addition, we showed that, at the dose used, only DHEA, DHEA-S and PREG-S had antidepressant effects. In conclusion, these results highly suggest that part of the HPA axis and antidepressant effects of neuroactive steroids could be mediated by BDNF, particularly at the amygdala level. They also suggest that neurosteroids effects on central BDNF could partially explain the trophic properties of these molecules.

  8. Low-level contrast statistics of natural images can modulate the frequency of event-related potentials (ERP in humans

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    Masoud Ghodrati

    2016-12-01

    Full Text Available Humans are fast and accurate in categorizing complex natural images. It is, however, unclear what features of visual information are exploited by brain to perceive the images with such speed and accuracy. It has been shown that low-level contrast statistics of natural scenes can explain the variance of amplitude of event-related potentials (ERP in response to rapidly presented images. In this study, we investigated the effect of these statistics on frequency content of ERPs. We recorded ERPs from human subjects, while they viewed natural images each presented for 70 ms. Our results showed that Weibull contrast statistics, as a biologically plausible model, explained the variance of ERPs the best, compared to other image statistics that we assessed. Our time-frequency analysis revealed a significant correlation between these statistics and ERPs’ power within theta frequency band (~3-7 Hz. This is interesting, as theta band is believed to be involved in context updating and semantic encoding. This correlation became significant at ~110 ms after stimulus onset, and peaked at 138 ms. Our results show that not only the amplitude but also the frequency of neural responses can be modulated with low-level contrast statistics of natural images and highlights their potential role in scene perception.

  9. The Orphan G Protein-coupled Receptor Gpr175 (Tpra40) Enhances Hedgehog Signaling by Modulating cAMP Levels.

    Science.gov (United States)

    Singh, Jaskirat; Wen, Xiaohui; Scales, Suzie J

    2015-12-04

    The Hedgehog (Hh) signaling pathway plays an essential role in vertebrate embryonic tissue patterning of many developing organs. Signaling occurs predominantly in primary cilia and is initiated by the entry of the G protein-coupled receptor (GPCR)-like protein Smoothened into cilia and culminates in gene transcription via the Gli family of transcription factors upon their nuclear entry. Here we identify an orphan GPCR, Gpr175 (also known as Tpra1 or Tpra40: transmembrane protein, adipocyte associated 1 or of 40 kDa), which also localizes to primary cilia upon Hh stimulation and positively regulates Hh signaling. Interaction experiments place Gpr175 at the level of PKA and upstream of the Gαi component of heterotrimeric G proteins, which itself localizes to cilia and can modulate Hh signaling. Gpr175 or Gαi1 depletion leads to increases in cellular cAMP levels and in Gli3 processing into its repressor form. Thus we propose that Gpr175 coupled to Gαi1 normally functions to inhibit the production of cAMP by adenylyl cyclase upon Hh stimulation, thus maximizing signaling by turning off PKA activity and hence Gli3 repressor formation. Taken together our data suggest that Gpr175 is a novel positive regulator of the Hh signaling pathway. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Selenite modulates the level of phenolics and nutrient element to alleviate the toxicity of arsenite in rice (Oryza sativa L.).

    Science.gov (United States)

    Chauhan, Reshu; Awasthi, Surabhi; Tripathi, Preeti; Mishra, Seema; Dwivedi, Sanjay; Niranjan, Abhishek; Mallick, Shekhar; Tripathi, Pratibha; Pande, Veena; Tripathi, Rudra Deo

    2017-04-01

    Arsenic (As) contamination of paddy rice is a serious threat all over the world particularly in South East Asia. Selenium (Se) plays important role in protection of plants against various abiotic stresses including heavy metals. Moreover, arsenite (AsIII) and selenite (SeIV) can be biologically antagonistic due to similar electronic configuration and sharing the common transporter for their uptake in plant. In the present study, the response of oxidative stress, phenolic compounds and nutrient elements was analyzed to investigate Se mediated As tolerance in rice seedlings during AsIII and SeIV exposure in hydroponics. Selenite (25µM) significantly decreased As accumulation in plant than As (25µM) alone treated plants. Level of oxidative stress related parameters viz., reactive oxygen species (ROS), lipid peroxidation, electrical conductivity, nitric oxide and pro-oxidant enzyme (NADPH oxidase), were in the order of As>As+Se>control>Se. Selenium ameliorated As phytotoxicity by increased level of phenolic compounds particularly gallic acid, protocatechuic acid, ferulic acid and rutin and thiol metabolism related enzymes viz., serine acetyl transferase (SAT) and cysteine synthase (CS). Selenium supplementation enhanced the uptake of nutrient elements viz., Fe, Mn, Co, Cu, Zn, Mo, and improved plant growth. The results concluded that Se addition in As contaminated environment might be an important strategy to reduce As uptake and associated phytotoxicity in rice plant by modulation of phenolic compounds and increased uptake of nutrient elements. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Resveratrol, by modulating RNA processing factor levels, can influence the alternative splicing of pre-mRNAs.

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    M Andrea Markus

    Full Text Available Alternative pre-mRNA splicing defects can contribute to, or result from, various diseases, including cancer. Aberrant mRNAs, splicing factors and other RNA processing factors have therefore become targets for new therapeutic interventions. Here we report that the natural polyphenol resveratrol can modulate alternative splicing in a target-specific manner. We transfected minigenes of several alternatively spliceable primary mRNAs into HEK293 cells in the presence or absence of 1, 5, 20 and 50 µM resveratrol and measured exon levels by semi-quantitative PCR after separation by agarose gel electrophoresis. We found that 20 µg/ml and 50 µg/ml of resveratrol affected exon inclusion of SRp20 and SMN2 pre-mRNAs, but not CD44v5 or tau pre-mRNAs. By Western blotting and immunofluorescence we showed that this effect may be due to the ability of resveratrol to change the protein level but not the localization of several RNA processing factors. The processing factors that increased significantly were ASF/SF2, hnRNPA1 and HuR, but resveratrol did not change the levels of RBM4, PTBP1 and U2AF35. By means of siRNA-mediated knockdown we depleted cells of SIRT1, regarded as a major target of resveratrol, and showed that the effect on splicing was not dependent on SIRT1. Our results suggest that resveratrol might be an attractive small molecule to treat diseases in which aberrant splicing has been implicated, and justify more extensive research on the effects of resveratrol on the splicing machinery.

  12. Resveratrol, by modulating RNA processing factor levels, can influence the alternative splicing of pre-mRNAs.

    Science.gov (United States)

    Markus, M Andrea; Marques, Francine Z; Morris, Brian J

    2011-01-01

    Alternative pre-mRNA splicing defects can contribute to, or result from, various diseases, including cancer. Aberrant mRNAs, splicing factors and other RNA processing factors have therefore become targets for new therapeutic interventions. Here we report that the natural polyphenol resveratrol can modulate alternative splicing in a target-specific manner. We transfected minigenes of several alternatively spliceable primary mRNAs into HEK293 cells in the presence or absence of 1, 5, 20 and 50 µM resveratrol and measured exon levels by semi-quantitative PCR after separation by agarose gel electrophoresis. We found that 20 µg/ml and 50 µg/ml of resveratrol affected exon inclusion of SRp20 and SMN2 pre-mRNAs, but not CD44v5 or tau pre-mRNAs. By Western blotting and immunofluorescence we showed that this effect may be due to the ability of resveratrol to change the protein level but not the localization of several RNA processing factors. The processing factors that increased significantly were ASF/SF2, hnRNPA1 and HuR, but resveratrol did not change the levels of RBM4, PTBP1 and U2AF35. By means of siRNA-mediated knockdown we depleted cells of SIRT1, regarded as a major target of resveratrol, and showed that the effect on splicing was not dependent on SIRT1. Our results suggest that resveratrol might be an attractive small molecule to treat diseases in which aberrant splicing has been implicated, and justify more extensive research on the effects of resveratrol on the splicing machinery.

  13. Clues to γ-secretase, huntingtin and Hirano body normal function using the model organism Dictyostelium discoideum

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    Myre Michael A

    2012-04-01

    Full Text Available Abstract Many neurodegenerative disorders, although related by their destruction of brain function, display remarkable cellular and/or regional pathogenic specificity likely due to a deregulated functionality of the mutant protein. However, neurodegenerative disease genes, for example huntingtin (HTT, the ataxins, the presenilins (PSEN1/PSEN2 are not simply localized to neurons but are ubiquitously expressed throughout peripheral tissues; it is therefore paramount to properly understand the earliest precipitating events leading to neuronal pathogenesis to develop effective long-term therapies. This means, in no unequivocal terms, it is crucial to understand the gene's normal function. Unfortunately, many genes are often essential for embryogenesis which precludes their study in whole organisms. This is true for HTT, the β-amyloid precursor protein (APP and presenilins, responsible for early onset Alzheimer's disease (AD. To better understand neurological disease in humans, many lower and higher eukaryotic models have been established. So the question arises: how reasonable is the use of organisms to study neurological disorders when the model of choice does not contain neurons? Here we will review the surprising, and novel emerging use of the model organism Dictyostelium discoideum, a species of soil-living amoeba, as a valuable biomedical tool to study the normal function of neurodegenerative genes. Historically, the evidence on the usefulness of simple organisms to understand the etiology of cellular pathology cannot be denied. But using an organism without a central nervous system to understand diseases of the brain? We will first introduce the life cycle of Dictyostelium, the presence of many disease genes in the genome and how it has provided unique opportunities to identify mechanisms of disease involving actin pathologies, mitochondrial disease, human lysosomal and trafficking disorders and host-pathogen interactions. Secondly, I will

  14. CTG repeat-targeting oligonucleotides for down-regulating Huntingtin expression

    DEFF Research Database (Denmark)

    Zaghloul, Eman M; Gissberg, Olof; Moreno, Pedro M D

    2017-01-01

    Huntington's disease (HD) is a fatal, neurodegenerative disorder in which patients suffer from mobility, psychological and cognitive impairments. Existing therapeutics are only symptomatic and do not significantly alter the disease progression or increase life expectancy. HD is caused by expansion....... Thus, reduction of both muHTT mRNA and protein levels would ideally be the most useful therapeutic option. We herein present a novel strategy for HD treatment using oligonucleotides (ONs) directly targeting the HTT trinucleotide repeat DNA. A partial, but significant and potentially long-term, HTT...

  15. A wafer-level multi-chip module process with thick photosensitive benzocyclobutene as the dielectric for microwave application

    International Nuclear Information System (INIS)

    Tang, Jiajie; Sun, Xiaowei; Luo, Le

    2011-01-01

    A wafer-level microwave multi-chip module (MMCM) packaging process is presented. Thick photosensitive-benzocyclobutene (photo-BCB) polymer (about 25 µm/layer) is used as the dielectric for its simplified process and the capability of obtaining desirable electrical, chemical and mechanical properties at high frequencies. The MMCM packaging structure contains a monolithic microwave integrated circuit (MMIC) chip embedded in a lossy-silicon wafer, a microwave band-pass filter (BPF) and two layers of BCB/Au interconnection. Key processes of fabrication are described in detail. The non-uniformity of BCB film and the sidewall angle of the via-holes for inter-layer connection are tested. Via-chains prepared by metal/BCB multilayer structures are tested through the Kelvin test structure to investigate the resistances of inter-layer connection. The average value is measured to be 73.5 mΩ. The electrical characteristic of this structure is obtained by a microwave transmission performance test from 15 to 30 GHz. The measurement results show good consistency between the bare MMIC die and the packaged die in the test frequency band. The gain of the MMIC chip after packaging is better than 18 dB within the designed operating frequency range (from 23 to 25 GHz). When the packaged MMIC chip is connected to a BPF, the maximum gain is still measured to reach 11.95 dB at 23.8 GHz

  16. Sense of Accomplishment Is Modulated by a Proper Level of Instruction and Represented in the Brain Reward System.

    Science.gov (United States)

    Nakai, Tomoya; Nakatani, Hironori; Hosoda, Chihiro; Nonaka, Yulri; Okanoya, Kazuo

    2017-01-01

    Problem-solving can be facilitated with instructions or hints, which provide information about given problems. The proper amount of instruction that should be provided for learners is controversial. Research shows that tasks with intermediate difficulty induce the largest sense of accomplishment (SA), leading to an intrinsic motivation for learning. To investigate the effect of instructions, we prepared three instruction levels (No hint, Indirect hint, and Direct hint) for the same insight-problem types. We hypothesized that indirect instructions impose intermediate difficulty for each individual, thereby inducing the greatest SA per person. Based on previous neuroimaging studies that showed involvement of the bilateral caudate in learning and motivation, we expected SA to be processed in this reward system. We recruited twenty-one participants, and investigated neural activations during problem solving by functional magnetic resonance imaging (fMRI). We confirmed that the Indirect hint, which imposed intermediate difficulty, induced the largest SA among the three instruction types. Using fMRI, we showed that activations in the bilateral caudate and anterior cingulate cortex (ACC) were significantly modulated by SA. In the bilateral caudate, the indirect hint induced the largest activation, while the ACC seemed to reflect the difference between correct and incorrect trials. Importantly, such activation pattern was independent of notations (number or letter). Our results indicate that SA is represented in the reward system, and that the Indirect instruction effectively induces such sensation.

  17. Silver ions increase plasma membrane permeability through modulation of intracellular calcium levels in tobacco BY-2 cells.

    Science.gov (United States)

    Klíma, Petr; Laňková, Martina; Vandenbussche, Filip; Van Der Straeten, Dominique; Petrášek, Jan

    2018-05-01

    Silver ions increase plasma membrane permeability for water and small organic compounds through their stimulatory effect on plasma membrane calcium channels, with subsequent modulation of intracellular calcium levels and ion homeostasis. The action of silver ions at the plant plasma membrane is largely connected with the inhibition of ethylene signalling thanks to the ability of silver ion to replace the copper cofactor in the ethylene receptor. A link coupling the action of silver ions and cellular auxin efflux has been suggested earlier by their possible direct interaction with auxin efflux carriers or by influencing plasma membrane permeability. Using tobacco BY-2 cells, we demonstrate here that besides a dramatic increase of efflux of synthetic auxins 2,4-dichlorophenoxyacetic acid (2,4-D) and 1-naphthalene acetic acid (NAA), treatment with AgNO 3 resulted in enhanced efflux of the cytokinin trans-zeatin (tZ) as well as the auxin structural analogues tryptophan (Trp) and benzoic acid (BA). The application of AgNO 3 was accompanied by gradual water loss and plasmolysis. The observed effects were dependent on the availability of extracellular calcium ions (Ca 2+ ) as shown by comparison of transport assays in Ca 2+ -rich and Ca 2+ -free buffers and upon treatment with inhibitors of plasma membrane Ca 2+ -permeable channels Al 3+ and ruthenium red, both abolishing the effect of AgNO 3 . Confocal microscopy of Ca 2+ -sensitive fluorescence indicator Fluo-4FF, acetoxymethyl (AM) ester suggested that the extracellular Ca 2+ availability is necessary to trigger the response to silver ions and that the intracellular Ca 2+ pool alone is not sufficient for this effect. Altogether, our data suggest that in plant cells the effects of silver ions originate from the primal modification of the internal calcium levels, possibly by their interaction with Ca 2+ -permeable channels at the plasma membrane.

  18. Intermittent fasting modulates IgA levels in the small intestine under intense stress: a mouse model.

    Science.gov (United States)

    Lara-Padilla, Eleazar; Godínez-Victoria, Marycarmen; Drago-Serrano, Maria Elisa; Reyna-Garfias, Humberto; Arciniega-Martínez, Ivonne Maciel; Abarca-Rojano, Edgar; Cruz-Hernández, Teresita Rocío; Campos-Rodríguez, Rafael

    2015-08-15

    Intermittent fasting prolongs the lifespan and unlike intense stress provides health benefits. Given the role of the immunoglobulin A (IgA) in the intestinal homeostasis, the aim of this study was to assess the impact of intermittent fasting plus intense stress on secretory IgA (SIgA) production and other mucosal parameters in the duodenum and ileum. Two groups of six mice, with intermittent fasting or fed ad libitum for 12weeks, were submitted to a session of intense stress by a bout of forced swimming. Unstressed ad libitum fed or intermittently fasted groups were included as controls. After sacrifice, we evaluated intestinal SIgA and plasma adrenal hormones, lamina propria IgA+ plasma-cells, mRNA expression of polymeric immunoglobulin receptor, α- and J-chains in the liver and intestinal mucosa, as well as pro- (tumor necrosis factor-α, interleukin-6 and Interferon-γ) and anti- (interleukin-2, -4, -10 and transforming growth factor-β) inflammatory cytokines in mucosal samples. Under intense stress, intermittent fasting down- or up-modulated the levels of most parameters in the duodenum and ileum, respectively while up-regulated corticosterone levels without affecting epinephrine. Our data suggest intermittent fasting plus intense stress elicited neuroendocrine pathways that differentially controlled IgA and pIgR expression in duodenum and ileum. These findings provide experimental foundations for a presumable impact of intermittent fasting under intense stress on the intestinal homeostasis or inflammation by triggering or reducing the IgA production in ileum or duodenum respectively. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Social, state-dependent and environmental modulation of faecal corticosteroid levels in free-ranging female spotted hyenas.

    Science.gov (United States)

    Goymann, W; East, M L; Wachter, B; Höner, O P; Möstl, E; Van't Hof, T J; Hofer, H

    2001-12-07

    Little is known about to what extent the sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis may be state dependent and vary in the same species between environments. Here we tested whether the faecal corticosteroid concentrations of matrilineal adult female spotted hyenas are influenced by social and reproductive status in adjacent ecosystems and whether they vary between periods with and without social stress. Females in the Serengeti National Park frequently become socially subordinate intruders in other hyena territories by undertaking long-distance foraging trips to migratory herds, whereas in the Ngorongoro Crater they usually forage inside their own small territories on resident prey. The faecal corticosteroid concentrations in Serengeti females were significantly higher than in Ngorongoro females. Energy expenditure by lactation is exceptionally high in spotted hyenas and this may be reflected in their corticosteroid levels. The faecal corticosteroid levels in both populations were higher in lactating than in non-lactating females. During periods of social stability, faecal corticosteroid concentrations increased in non-lactating females but not in lactating females as social status declined. Lactating Serengeti females had significantly higher faecal corticosteroid concentrations during periods with acute severe social stress than during periods without, indicating that the HPA axis is sensitive to social stimuli even in lactating females. So far few studies have used non-invasive monitoring methods for assessing social stress in freeranging animals. This study demonstrates for the first time, to the authors' knowledge, that corticosteroid concentrations may differ between periods with and without social stress for a free-ranging female mammal and that the modulating effect of social status may depend on reproductive status.

  20. Short-term sleep deprivation impairs spatial working memory and modulates expression levels of ionotropic glutamate receptor subunits in hippocampus.

    Science.gov (United States)

    Xie, Meilan; Yan, Jie; He, Chao; Yang, Li; Tan, Gang; Li, Chao; Hu, Zhian; Wang, Jiali

    2015-06-01

    Hippocampus-dependent learning memory is sensitive to sleep deprivation (SD). Although the ionotropic glutamate receptors play a vital role in synaptic plasticity and learning and memory, however, whether the expression of these receptor subunits is modulated by sleep loss remains unclear. In the present study, western blotting was performed by probing with specific antibodies against the ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits GluA1, GluA2, GluA3, and against the N-methyl-d-aspartate (NMDA) glutamate receptor subunits GluN1, GluN2A, GluN2B. In hippocampus, down regulation of surface GluA1 and GluN2A surface expression were observed in both SD groups. However, surface expression level of GluA2, GluA3, GluN1 and GluN2B was significantly up-regulated in 8h-SD rats when compared to the 4h-SD rats. In parallel with the complex changes in AMPA and NMDA receptor subunit expressions, we found the 8h-SD impaired rat spatial working memory in 30-s-delay T-maze task, whereas no impairment of spatial learning was observed in 4h-SD rats. These results indicate that sleep loss alters the relative expression levels of the AMPA and NMDA receptors, thus affects the synaptic strength and capacity for plasticity and partially contributes to spatial memory impairment. Copyright © 2015. Published by Elsevier B.V.

  1. Abalone visceral extract inhibit tumor growth and metastasis by modulating Cox-2 levels and CD8+ T cell activity

    Directory of Open Access Journals (Sweden)

    II Kim Jae

    2010-10-01

    Full Text Available Abstract Background Abalone has long been used as a valuable food source in East Asian countries. Although the nutritional importance of abalone has been reported through in vitro and in vivo studies, there is little evidence about the potential anti-tumor effects of abalone visceral extract. The aim of the present study is to examine anti-tumor efficacy of abalone visceral extract and to elucidate its working mechanism. Methods In the present study, we used breast cancer model using BALB/c mouse-derived 4T1 mammary carcinoma and investigated the effect of abalone visceral extract on tumor development. Inhibitory effect against tumor metastasis was assessed by histopathology of lungs. Cox-2 productions by primary and secondary tumor were measured by real-time RT-PCR and immunoblotting (IB. Proliferation assay based on [3H]-thymidine incorporation and measurement of cytokines and effector molecules by RT-PCR were used to confirm tumor suppression efficacy of abalone visceral extract by modulating cytolytic CD8+ T cells. The cytotoxicity of CD8+ T cell was compared by JAM test. Results Oral administration of abalone visceral extract reduced tumor growth (tumor volume and weight and showed reduced metastasis as confirmed by decreased level of splenomegaly (spleen size and weight and histological analysis of the lung metastasis (gross analysis and histological staining. Reduced expression of Cox-2 (mRNA and protein from primary tumor and metastasized lung was also detected. In addition, treatment of abalone visceral extract increased anti-tumor activities of CD8+ T cells by increasing the proliferation capacity and their cytolytic activity. Conclusions Our results suggest that abalone visceral extract has anti-tumor effects by suppressing tumor growth and lung metastasis through decreasing Cox-2 expression level as well as promoting proliferation and cytolytic function of CD8+ T cells.

  2. Abalone visceral extract inhibit tumor growth and metastasis by modulating Cox-2 levels and CD8+ T cell activity.

    Science.gov (United States)

    Lee, Choong-Gu; Kwon, Ho-Keun; Ryu, Jae Ha; Kang, Sung Jin; Im, Chang-Rok; Ii Kim, Jae; Im, Sin-Hyeog

    2010-10-20

    Abalone has long been used as a valuable food source in East Asian countries. Although the nutritional importance of abalone has been reported through in vitro and in vivo studies, there is little evidence about the potential anti-tumor effects of abalone visceral extract. The aim of the present study is to examine anti-tumor efficacy of abalone visceral extract and to elucidate its working mechanism. In the present study, we used breast cancer model using BALB/c mouse-derived 4T1 mammary carcinoma and investigated the effect of abalone visceral extract on tumor development. Inhibitory effect against tumor metastasis was assessed by histopathology of lungs. Cox-2 productions by primary and secondary tumor were measured by real-time RT-PCR and immunoblotting (IB). Proliferation assay based on [3H]-thymidine incorporation and measurement of cytokines and effector molecules by RT-PCR were used to confirm tumor suppression efficacy of abalone visceral extract by modulating cytolytic CD8+ T cells. The cytotoxicity of CD8+ T cell was compared by JAM test. Oral administration of abalone visceral extract reduced tumor growth (tumor volume and weight) and showed reduced metastasis as confirmed by decreased level of splenomegaly (spleen size and weight) and histological analysis of the lung metastasis (gross analysis and histological staining). Reduced expression of Cox-2 (mRNA and protein) from primary tumor and metastasized lung was also detected. In addition, treatment of abalone visceral extract increased anti-tumor activities of CD8+ T cells by increasing the proliferation capacity and their cytolytic activity. Our results suggest that abalone visceral extract has anti-tumor effects by suppressing tumor growth and lung metastasis through decreasing Cox-2 expression level as well as promoting proliferation and cytolytic function of CD8+ T cells.

  3. Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels.

    Science.gov (United States)

    Horvath, Steve; Langfelder, Peter; Kwak, Seung; Aaronson, Jeff; Rosinski, Jim; Vogt, Thomas F; Eszes, Marika; Faull, Richard L M; Curtis, Maurice A; Waldvogel, Henry J; Choi, Oi-Wa; Tung, Spencer; Vinters, Harry V; Coppola, Giovanni; Yang, X William

    2016-07-01

    Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=-0.41, p=5.5×10-8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels.

  4. Dietary composition modulates brain mass and solubilizable Aβ levels in a mouse model of aggressive Alzheimer's amyloid pathology

    Directory of Open Access Journals (Sweden)

    Buxbaum Joseph D

    2009-10-01

    Full Text Available Abstract Objective Alzheimer's disease (AD is a progressive neurodegenerative disease of the central nervous system (CNS. Recently, an increased interest in the role diet plays in the pathology of AD has resulted in a focus on the detrimental effects of diets high in cholesterol and fat and the beneficial effects of caloric restriction. The current study examines how dietary composition modulates cerebral amyloidosis and neuronal integrity in the TgCRND8 mouse model of AD. Methods From 4 wks until 18 wks of age, male and female TgCRND8 mice were maintained on one of four diets: (1 reference (regular commercial chow; (2 high fat/low carbohydrate custom chow (60 kcal% fat/30 kcal% protein/10 kcal% carbohydrate; (3 high protein/low carbohydrate custom chow (60 kcal% protein/30 kcal% fat/10 kcal% carbohydrate; or (4 high carbohydrate/low fat custom chow (60 kcal% carbohydrate/30 kcal% protein/10 kcal% fat. At age 18 wks, mice were sacrificed, and brains studied for (a wet weight; (b solubilizable Aβ content by ELISA; (c amyloid plaque burden; (d stereologic analysis of selected hippocampal subregions. Results Animals receiving a high fat diet showed increased brain levels of solubilizable Aβ, although we detected no effect on plaque burden. Unexpectedly, brains of mice fed a high protein/low carbohydrate diet were 5% lower in weight than brains from all other mice. In an effort to identify regions that might link loss of brain mass to cognitive function, we studied neuronal density and volume in hippocampal subregions. Neuronal density and volume in the hippocampal CA3 region of TgCRND8 mice tended to be lower in TgCRND8 mice receiving the high protein/low carbohydrate diet than in those receiving the regular chow. Neuronal density and volume were preserved in CA1 and in the dentate gyrus. Interpretation Dissociation of Aβ changes from brain mass changes raises the possibility that diet plays a role not only in modulating amyloidosis but also in

  5. Attention, working memory, and phenomenal experience of WM content: memory levels determined by different types of top-down modulation

    OpenAIRE

    Jacob, Jane; Jacobs, Christianne; Silvanto, Juha

    2015-01-01

    What is the role of top-down attentional modulation in consciously accessing working memory (WM) content? In influential WM models, information can exist in different states, determined by allocation of attention; placing the original memory representation in the center of focused attention gives rise to conscious access. Here we discuss various lines of evidence indicating that such attentional modulation is not sufficient for memory content to be phenomenally experienced. We propose that, i...

  6. Levels of Interference in Long and Short-Term Memory Differentially Modulate Non-REM and REM Sleep.

    Science.gov (United States)

    Fraize, Nicolas; Carponcy, Julien; Joseph, Mickaël Antoine; Comte, Jean-Christophe; Luppi, Pierre-Hervé; Libourel, Paul-Antoine; Salin, Paul-Antoine; Malleret, Gaël; Parmentier, Régis

    2016-12-01

    It is commonly accepted that sleep is beneficial to memory processes, but it is still unclear if this benefit originates from improved memory consolidation or enhanced information processing. It has thus been proposed that sleep may also promote forgetting of undesirable and non-essential memories, a process required for optimization of cognitive resources. We tested the hypothesis that non-rapid eye movement sleep (NREMS) promotes forgetting of irrelevant information, more specifically when processing information in working memory (WM), while REM sleep (REMS) facilitates the consolidation of important information. We recorded sleep patterns of rats trained in a radial maze in three different tasks engaging either the long-term or short-term storage of information, as well as a gradual level of interference. We observed a transient increase in REMS amount on the day the animal learned the rule of a long-term/reference memory task (RM), and, in contrast, a positive correlation between the performance of rats trained in a WM task involving an important processing of interference and the amount of NREMS or slow wave activity. Various oscillatory events were also differentially modulated by the type of training involved. Notably, NREMS spindles and REMS rapid theta increase with RM training, while sharp-wave ripples increase with all types of training. These results suggest that REMS, but also rapid oscillations occurring during NREMS would be specifically implicated in the long-term memory in RM, whereas NREMS and slow oscillations could be involved in the forgetting of irrelevant information required for WM. © 2016 Associated Professional Sleep Societies, LLC.

  7. Environmental modulation of androgen levels and secondary sex characters in two populations of the peacock blenny Salaria pavo.

    Science.gov (United States)

    Saraiva, João L; Gonçalves, David M; Oliveira, Rui F

    2010-02-01

    Morphology and endocrinology were studied in two populations of the peacock blenny Salaria pavo, with different regimes of sexual selection imposed by differences in nest site availability. The peacock blenny is a small, sexually dimorphic benthic fish that presents exclusive paternal care of the clutch and inhabits rocky shores of the Mediterranean and adjacent Atlantic areas. In a population from the Gulf of Trieste (Northern Adriatic sea) inhabiting rocky shores where nest sites are abundant, male-male competition for nests is low, males court females and a low frequency of alternative reproductive tactics (small, parasitic female-mimicking sneaker males that change tactic into nest holders in subsequent breeding seasons) occurs. Conversely at Ria Formosa, a coastal lagoon in Southern Portugal, where nest sites are scarce and highly aggregated, male-male competition for nests is very high, there is sex-role reversal with female courtship and a high frequency of alternative reproductive tactics is observed. Concomitantly, at Ria Formosa nest holder males are larger and present more developed secondary sex characters and higher levels of 11KT than at the Gulf of Trieste. However, the gonads of nest holders and parasitic males were larger in the Gulf of Trieste population. Competition for nests at Ria Formosa seems to promote more developed secondary sex characters in nest site scarcity conditions, while competition for females at the Gulf of Trieste seems to be spurring sperm competition among males in populations where nest sites are more abundant. 11KT was thus associated with the development and expression of secondary sex characters in contrasting environments. These results exemplify how the modulation of behavioral plasticity and secondary sex characters by the social environment can be mediated by androgens. Copyright 2009 Elsevier Inc. All rights reserved.

  8. A wafer-level 3D packaging structure with Benzocyclobutene as a dielectric for multichip module fabrication

    International Nuclear Information System (INIS)

    Geng Fei; Ding Xiaoyun; Xu Gaowei; Luo Le

    2009-01-01

    A new wafer-level 3D packaging structure with Benzocyclobutene (BCB) as interlayer dielectrics (ILDs) for multichip module fabrication is proposed for application in the Ku-band wave. The packaging structure consists of two layers of BCB films and three layers of metallized films, in which the monolithic microwave IC (MMIC), thin film resistors, striplines and microstrip lines are integrated. Wet etched cavities fabricated on the silicon substrate are used for mounting active and passive components. BCB layers cover the components and serve as ILDs for interconnections. Gold bumps are used as electric interconnections between different layers, which eliminates the need to prepare vias by costly dry etching and deposition processes. In order to get high-quality BCB films for the subsequent chemical mechanical planarization (CMP) and multilayer metallization processes, the BCB curing profile is optimized and the roughness of the BCB film after the CMP process is kept lower than 10 nm. The thermal, mechanical and electrical properties of the packaging structure are investigated. The thermal resistance can be controlled below 2 0 C/W. The average shear strength of the gold bumps on the BCB surface is around 70 N/mm 2 . The performances of MMIC and interconnection structure at high frequencies are optimized and tested. The S-parameters curves of the packaged MMIC shift slightly showing perfect transmission character. The insertion loss change after the packaging process is less than 1 dB range at the operating frequency and the return loss is less than -8 dB from 10 to 15 GHz.

  9. Glutamate and Opioid Antagonists Modulate Dopamine Levels Evoked by Innately Attractive Male Chemosignals in the Nucleus Accumbens of Female Rats.

    Science.gov (United States)

    Sánchez-Catalán, María-José; Orrico, Alejandro; Hipólito, Lucía; Zornoza, Teodoro; Polache, Ana; Lanuza, Enrique; Martínez-García, Fernando; Granero, Luis; Agustín-Pavón, Carmen

    2017-01-01

    Sexual chemosignals detected by vomeronasal and olfactory systems mediate intersexual attraction in rodents, and act as a natural reinforcer to them. The mesolimbic pathway processes natural rewards, and the nucleus accumbens receives olfactory information via glutamatergic projections from the amygdala. Thus, the aim of this study was to investigate the involvement of the mesolimbic pathway in the attraction toward sexual chemosignals. Our data show that female rats with no previous experience with males or their chemosignals display an innate preference for male-soiled bedding. Focal administration of the opioid antagonist β-funaltrexamine into the posterior ventral tegmental area does not affect preference for male chemosignals. Nevertheless, exposure to male-soiled bedding elicits an increase in dopamine efflux in the nucleus accumbens shell and core, measured by microdialysis. Infusion of the opioid antagonist naltrexone in the accumbens core does not significantly affect dopamine efflux during exposure to male chemosignals, although it enhances dopamine levels 40 min after withdrawal of the stimuli. By contrast, infusion of the glutamate antagonist kynurenic acid in the accumbens shell inhibits the release of dopamine and reduces the time that females spend investigating male-soiled bedding. These data are in agreement with previous reports in male rats showing that exposure to opposite-sex odors elicits dopamine release in the accumbens, and with data in female mice showing that the behavioral preference for male chemosignals is not affected by opioidergic antagonists. We hypothesize that glutamatergic projections from the amygdala into the accumbens might be important to modulate the neurochemical and behavioral responses elicited by sexual chemosignals in rats.

  10. AAV-mediated delivery of the transcription factor XBP1s into the striatum reduces mutant Huntingtin aggregation in a mouse model of Huntington’s disease

    International Nuclear Information System (INIS)

    Zuleta, Amparo; Vidal, Rene L.; Armentano, Donna; Parsons, Geoffrey; Hetz, Claudio

    2012-01-01

    Highlights: ► The contribution of ER stress to HD has not been directly addressed. ► Expression of XBP1s using AAVs decreases Huntingtin aggregation in vivo. ► We describe a new in vivo model of HD based on the expression of a large fragment of mHtt-RFP. -- Abstract: Huntington’s disease (HD) is caused by mutations that expand a polyglutamine region in the amino-terminal domain of Huntingtin (Htt), leading to the accumulation of intracellular inclusions and progressive neurodegeneration. Recent reports indicate the engagement of endoplasmic reticulum (ER) stress responses in human HD post mortem samples and animal models of the disease. Adaptation to ER stress is mediated by the activation of the unfolded protein response (UPR), an integrated signal transduction pathway that attenuates protein folding stress by controlling the expression of distinct transcription factors including X-Box binding protein 1 (XBP1). Here we targeted the expression of XBP1 on a novel viral-based model of HD. We delivered an active form of XBP1 locally into the striatum of adult mice using adeno-associated vectors (AAVs) and co-expressed this factor with a large fragment of mutant Htt as a fusion protein with RFP (Htt588 Q95 -mRFP) to directly visualize the accumulation of Htt inclusions in the brain. Using this approach, we observed a significant reduction in the accumulation of Htt588 Q95 -mRFP intracellular inclusion when XBP1 was co-expressed in the striatum. These results contrast with recent findings indicating a protective effect of XBP1 deficiency in neurodegeneration using knockout mice, and suggest a potential use of gene therapy strategies to manipulate the UPR in the context of HD.

  11. Analysis of proteolytic processes and enzymatic activities in the generation of huntingtin n-terminal fragments in an HEK293 cell model.

    Directory of Open Access Journals (Sweden)

    Andrew T N Tebbenkamp

    Full Text Available N-terminal fragments of mutant huntingtin (htt that terminate between residues 90-115, termed cleavage product A or 1 (cp-A/1, form intracellular and intranuclear inclusion bodies in the brains of patients with Huntington's disease (HD. These fragments appear to be proteolytic products of the full-length protein. Here, we use an HEK293 cell culture model to investigate huntingtin proteolytic processing; previous studies of these cells have demonstrated cleavage of htt to cp-A/1 like htt fragments.Recombinant N-terminal htt fragments, terminating at residue 171 (also referred to as cp-B/2 like, were efficiently cleaved to produce cp-A/1 whereas fragments representing endogenous caspase, calpain, and metalloproteinase cleavage products, terminating between residues 400-600, were inefficiently cleaved. Using cysteine-labeling techniques and antibody binding mapping, we localized the C-terminus of the cp-A/1 fragments produced by HEK293 cells to sequences minimally limited by cysteine 105 and an antibody epitope composed of residues 115-124. A combination of genetic and pharmacologic approaches to inhibit potential proteases, including γ-secretase and calpain, proved ineffective in preventing production of cp-A/1.Our findings indicate that HEK293 cells express a protease that is capable of efficiently cleaving cp-B/2 like fragments of htt with normal or expanded glutamine repeats. For reasons that remain unclear, this protease cleaves longer htt fragments, with normal or expanded glutamine expansions, much less efficiently. The protease in HEK293 cells that is capable of generating a cp-A/1 like htt fragment may be a novel protease with a high preference for a cp-B/2-like htt fragment as substrate.

  12. Self-synchronization of the modulation of energy-levels population with electrons in GaAs induced by picosecond pulses of probe radiation and intrinsic stimulated emission

    Energy Technology Data Exchange (ETDEWEB)

    Ageeva, N. N.; Bronevoi, I. L., E-mail: bil@cplire.ru; Zabegaev, D. N.; Krivonosov, A. N. [Russian Academy of Sciences, Kotel’nikov Institute of Radioengineering and Electronics (Russian Federation)

    2016-10-15

    Picosecond optical pumping leads to the initiation of intrinsic picosecond stimulated emission in GaAs. As was established previously, due to the interaction of pulses of probe radiation with those of intrinsic emission, the dependence of the absorption α of the probe pulse on its delay τ with respect to the pump pulse is modulated with oscillations. It is found that the oscillatory dependences α(τ) have a similar shape only in the case of certain combinations of energies of the interacting pulses. As a result, it is assumed that the above interaction is, in fact, a synchronization of modulations (formed by pulses) of charge-carrier populations at energy levels; this synchronization occurs in the direction of the reconstruction of detailed equilibrium. The real-time picosecond self-modulation of the absorption α is measured for the first time. The characteristics of this self-modulation as well as absorption α and intrinsic emission self-modulation characteristics measured previously by correlation methods are now accounted for by the concept of synchronization.

  13. Effect of modulation p-doping level on multi-state lasing in InAs/InGaAs quantum dot lasers having different external loss

    Science.gov (United States)

    Korenev, V. V.; Savelyev, A. V.; Maximov, M. V.; Zubov, F. I.; Shernyakov, Yu. M.; Kulagina, M. M.; Zhukov, A. E.

    2017-09-01

    The influence of the modulation p-doping level on multi-state lasing in InAs/InGaAs quantum dot (QD) lasers is studied experimentally for devices having various external losses. It is shown that in the case of short cavities (high external loss), there is an increase in the lasing power component corresponding to the ground-state optical transitions of QDs as the p-doping level grows. However, in the case of long cavities (small external loss), higher dopant concentrations may have an opposite effect on the output power. Based on these observations, an optimal design of laser geometry and an optimal doping level are discussed.

  14. Modelling the Interaction Levels in HCI Using an Intelligent Hybrid System with Interactive Agents: A Case Study of an Interactive Museum Exhibition Module in Mexico

    Directory of Open Access Journals (Sweden)

    Ricardo Rosales

    2018-03-01

    Full Text Available Technology has become a necessity in our everyday lives and essential for completing activities we typically take for granted; technologies can assist us by completing set tasks or achieving desired goals with optimal affect and in the most efficient way, thereby improving our interactive experiences. This paper presents research that explores the representation of user interaction levels using an intelligent hybrid system approach with agents. We evaluate interaction levels of Human-Computer Interaction (HCI with the aim of enhancing user experiences. We consider the description of interaction levels using an intelligent hybrid system to provide a decision-making system to an agent that evaluates interaction levels when using interactive modules of a museum exhibition. The agents represent a high-level abstraction of the system, where communication takes place between the user, the exhibition and the environment. In this paper, we provide a means to measure the interaction levels and natural behaviour of users, based on museum user-exhibition interaction. We consider that, by analysing user interaction in a museum, we can help to design better ways to interact with exhibition modules according to the properties and behaviour of the users. An interaction-evaluator agent is proposed to achieve the most suitable representation of the interaction levels with the aim of improving user interactions to offer the most appropriate directions, services, content and information, thereby improving the quality of interaction experienced between the user-agent and exhibition-agent.

  15. Generation of induced pluripotent stem cells from transgenic minipigs expressing the N-terminal part of the human mutant huntingtin - a new way to study pathogenesis of Huntington´s disease

    Czech Academy of Sciences Publication Activity Database

    Lišková, Irena; Vodička, P.; Juhás, Štefan; Klempíř, J.; Motlík, Jan

    2015-01-01

    Roč. 78, Suppl 2 (2015), s. 18-19 ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. 08.11.2015-10.11.2015, Liblice] R&D Projects: GA MŠk ED2.1.00/03.0124; GA MŠk(CZ) 7F14308 Institutional support: RVO:67985904 Keywords : Huntington ´s disease * huntingtin * induced pluripotent stem cells Subject RIV: FH - Neurology

  16. A Modified Multiband Hysteresis Controlled DTC of Induction Machine with 27-level asymmetrical CHB-MLI with NVC modulation

    Directory of Open Access Journals (Sweden)

    Rohith Balaji Jonnala

    2018-03-01

    Full Text Available The influence of Direct Torque Controlled Induction Motor Drive in the area of industrial application is very high; it presents foremost area of controllability of load at different states of operation. The major snags to the controller are maintaining Constant Switching Frequency and Infeasibility state. This paper concentrates on rectifying these problems with Modified Multiband Hysteresis Controller and Nearest Vector Control Modulated Asymmetrical Cascaded H-Bridge Multilevel Inverter for the better drive operation. In this case proper modification in MHC gives the optimal utilizations of each control vector to avoid the infeasibility states with a Lookup-Table and Multilevel Inverter gives more number of control voltage vectors with constant switching frequency for flexible operation of drive with low disturbances. Direct Torque Control equipped with these two modules achieves better operating conditions with low Torque ripples, low distorted flux and speed with different loads, and all other satisfactory load operating parameters.

  17. Investigation of the feasibility of elective irradiation to neck level Ib using intensity-modulated radiotherapy for patients with nasopharyngeal carcinoma: a retrospective analysis

    International Nuclear Information System (INIS)

    Zhang, Fan; Cheng, Yi-Kan; Li, Wen-Fei; Guo, Rui; Chen, Lei; Sun, Ying; Mao, Yan-Ping; Zhou, Guan-Qun; Liu, Xu; Liu, Li-Zhi; Lin, Ai-Hua; Tang, Ling-Long; Ma, Jun

    2015-01-01

    To assess the feasibility of elective neck irradiation to level Ib in nasopharyngeal carcinoma (NPC) using intensity-modulated radiation therapy (IMRT). We retrospectively analyzed 1438 patients with newly-diagnosed, non-metastatic and biopsy-proven NPC treated with IMRT. Greatest dimension of level IIa LNs (DLN-IIa) ≥ 20 mm and/or level IIa LNs with extracapsular spread (ES), oropharynx involvement and positive bilateral cervical lymph nodes (CLNs) were independently significantly associated with metastasis to level Ib LN at diagnosis. No recurrence at level Ib was observed in the 904 patients without these characteristics (median follow-up, 38.7 months; range, 1.3–57.8 months), these patients were classified as low risk. Level Ib irradiation was not an independent risk factor for locoregional failure-free survival, distant failure-free survival, failure-free survival or overall survival in low risk patients. The frequency of grade ≥ 2 subjective xerostomia at 12 months after radiotherapy was not significantly different between low risk patients who received level Ib-sparing, unilateral level Ib-covering or bilateral level Ib-covering IMRT. Level Ib-sparing IMRT should be safe and feasible for patients without a DLN-IIa ≥ 20 mm and/or level IIa LNs with ES, positive bilateral CLNs or oropharynx involvement at diagnosis. Further investigations based on specific criteria for dose constraints for the submandibular glands are warranted to confirm the benefit of elective level Ib irradiation

  18. Low-Level Test of the New Read-Out-Driver (ROD) Module and Back-of-Crate (BOC) Module for ATLAS IBL Data Acquisition System Upgrade

    CERN Document Server

    Hanindhito, Bagus

    2014-01-01

    During first long shutdown of The Large Hadron Collider, most of experiment infrastructures at CERN will be upgraded for preparation to operate at higher energy thus can open new possibilities to discover the unknown in particle physics. ATLAS, which is the biggest particle detector at CERN, will also be upgraded by constructing new pixel sensor layer. This new pixel sensor layer is called ATLAS Insertable B-Layer (IBL). IBL will be installed between the existing pixel sensor and new, smaller radius beam pipe. The installation of IBL will introduce new level of radiation and pixel occupancy. Therefore, it requires development of new technologies to supports the ATLAS IBL upgrade and also improve the physics performance of the existing pixel sensor. One of the important key technologies that must be upgraded is data acquisition system. The development of new front-end ASIC, the FE-I4, to answer the challenge in data acquisition system will require new off-detector electronics. The new off-detector electronics ...

  19. Chaperone protein HYPK interacts with the first 17 amino acid region of Huntingtin and modulates mutant HTT-mediated aggregation and cytotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Choudhury, Kamalika Roy [Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064 (India); Centre for Neuroscience, Indian Institute of Science, Bangalore 560012 (India); Bhattacharyya, Nitai P., E-mail: nitai_sinp@yahoo.com [Biomedical Genomics Centre, PG Polyclinic Building, 5, Suburbun Hospital Road, Kolkata 700020 (India)

    2015-01-02

    Highlights: • HYPK reduces mutant HTT-mediated aggregate formation and cytotoxicity. • Interaction of HYPK with HTT requires N-terminal 17 amino acid of HTT (HTT-N17). • Deletion of HTT-N17 leads to SDS-soluble, smaller, nuclear aggregates. • These smaller aggregates do not associate with HYPK and are more cytotoxic. • Maybe, interaction of HYPK with amphipathic HTT-N17 block HTT aggregate formation. - Abstract: Huntington’s disease is a polyglutamine expansion disorder, characterized by mutant HTT-mediated aggregate formation and cytotoxicity. Many reports suggests roles of N-terminal 17 amino acid domain of HTT (HTT-N17) towards subcellular localization, aggregate formation and subsequent pathogenicity induced by N-terminal HTT harboring polyQ stretch in pathogenic range. HYPK is a HTT-interacting chaperone which can reduce N-terminal mutant HTT-mediated aggregate formation and cytotoxicity in neuronal cell lines. However, how HYPK interacts with N-terminal fragment of HTT remained unknown. Here we report that specific interaction of HYPK with HTT-N17 is crucial for the chaperone activity of HYPK. Deletion of HTT-N17 leads to formation of tinier, SDS-soluble nuclear aggregates formed by N-terminal mutant HTT. The increased cytotoxicity imparted by these tiny aggregates might be contributed due to loss of interaction with HYPK.

  20. Xyloketal-derived small molecules show protective effect by decreasing mutant Huntingtin protein aggregates in Caenorhabditis elegans model of Huntington’s disease

    Directory of Open Access Journals (Sweden)

    Zeng YX

    2016-04-01

    Full Text Available Yixuan Zeng,1,2,* Wenyuan Guo,1,* Guangqing Xu,3 Qinmei Wang,4 Luyang Feng,1,2 Simei Long,1 Fengyin Liang,1 Yi Huang,1 Xilin Lu,1 Shichang Li,5 Jiebin Zhou,5 Jean-Marc Burgunder,6 Jiyan Pang,5 Zhong Pei1,2 1Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Disease, The First Affiliated Hospital, Sun Yat-sen University, 2Guangzhou Center, Chinese Huntington’s Disease Network, 3Department of Rehabilitation, The First Affiliated Hospital, 4Key laboratory on Assisted Circulation, Ministry of Health, Department of Cardiovascular Medicine of the First Affiliated Hospital, 5School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 6Swiss Huntington’s Disease Center, Department of Neurology, University of Bern, Bern, Switzerland *These authors contributed equally to this work Abstract: Huntington’s disease is an autosomal-dominant neurodegenerative disorder, with chorea as the most prominent manifestation. The disease is caused by abnormal expansion of CAG codon repeats in the IT15 gene, which leads to the expression of a glutamine-rich protein named mutant Huntingtin (Htt. Because of its devastating disease burden and lack of valid treatment, development of more effective therapeutics for Huntington’s disease is urgently required. Xyloketal B, a natural product from mangrove fungus, has shown protective effects against toxicity in other neurodegenerative disease models such as Parkinson’s and Alzheimer’s diseases. To identify potential neuroprotective molecules for Huntington’s disease, six derivatives of xyloketal B were screened in a Caenorhabditis elegans Huntington’s disease model; all six compounds showed a protective effect. Molecular docking studies indicated that compound 1 could bind to residues GLN369 and GLN393 of the mutant Htt protein, forming a

  1. Visual working memory modulates low-level saccade target selection: Evidence from rapidly generated saccades in the global effect paradigm

    Science.gov (United States)

    Hollingworth, Andrew; Matsukura, Michi; Luck, Steven J.

    2013-01-01

    In three experiments, we examined the influence of visual working memory (VWM) on the metrics of saccade landing position in a global effect paradigm. Participants executed a saccade to the more eccentric object in an object pair appearing on the horizontal midline, to the left or right of central fixation. While completing the saccade task, participants maintained a color in VWM for an unrelated memory task. Either the color of the saccade target matched the memory color (target match), the color of the distractor matched the memory color (distractor match), or the colors of neither object matched the memory color (no match). In the no-match condition, saccades tended to land at the midpoint between the two objects: the global, or averaging, effect. However, when one of the two objects matched VWM, the distribution of landing position shifted toward the matching object, both for target match and for distractor match. VWM modulation of landing position was observed even for the fastest quartile of saccades, with a mean latency as low as 112 ms. Effects of VWM on such rapidly generated saccades, with latencies in the express-saccade range, indicate that VWM interacts with the initial sweep of visual sensory processing, modulating perceptual input to oculomotor systems and thereby biasing oculomotor selection. As a result, differences in memory match produce effects on landing position similar to the effects generated by differences in physical salience. PMID:24190909

  2. Visual working memory modulates low-level saccade target selection: evidence from rapidly generated saccades in the global effect paradigm.

    Science.gov (United States)

    Hollingworth, Andrew; Matsukura, Michi; Luck, Steven J

    2013-11-04

    In three experiments, we examined the influence of visual working memory (VWM) on the metrics of saccade landing position in a global effect paradigm. Participants executed a saccade to the more eccentric object in an object pair appearing on the horizontal midline, to the left or right of central fixation. While completing the saccade task, participants maintained a color in VWM for an unrelated memory task. Either the color of the saccade target matched the memory color (target match), the color of the distractor matched the memory color (distractor match), or the colors of neither object matched the memory color (no match). In the no-match condition, saccades tended to land at the midpoint between the two objects: the global, or averaging, effect. However, when one of the two objects matched VWM, the distribution of landing position shifted toward the matching object, both for target match and for distractor match. VWM modulation of landing position was observed even for the fastest quartile of saccades, with a mean latency as low as 112 ms. Effects of VWM on such rapidly generated saccades, with latencies in the express-saccade range, indicate that VWM interacts with the initial sweep of visual sensory processing, modulating perceptual input to oculomotor systems and thereby biasing oculomotor selection. As a result, differences in memory match produce effects on landing position similar to the effects generated by differences in physical salience.

  3. In Women with Previous Pregnancy Hypertension, Levels of Cardiovascular Risk Biomarkers May Be Modulated by Haptoglobin Polymorphism

    Directory of Open Access Journals (Sweden)

    Andreia Matos

    2014-01-01

    Full Text Available Preeclampsia (PE may affect the risk for future cardiovascular disease. Haptoglobin (Hp, an acute phase protein with functional genetic polymorphism, synthesized in the hepatocyte and in many peripheral tissues secondary of oxidative stress of PE, may modulate that risk through the antioxidant, angiogenic, and anti-inflammatory differential effects of their genotypes. We performed a prospective study in 352 women aged 35±5.48 years, which 165 had previous PE, 2 to 16 years ago. We studied demographic, anthropometric, and haemodynamic biomarkers such as C-reactive protein (CRP, myeloperoxidase (MPO, and nitric oxide metabolites (total and nitrites, and others associated with liver function (AST and ALT and lipid profile (total LDL and cholesterol HDL, non-HDL, and apolipoproteins A and B. Finally, we study the influence of Hp genetic polymorphism on all these biomarkers and as a predisposing factor for PE and its remote cardiovascular disease prognosis. Previously preeclamptic women either hypertensive or normotensive presented significant differences in those risk biomarkers (MPO, nitrites, and ALT, whose variation may be modulated by Hp 1/2 functional genetic polymorphism. The history of PE may be relevant, in association with these biomarkers to the cardiovascular risk in premenopausal women.

  4. Comprehensive Loss Evaluation of Neutral-Point-Clamped (NPC) and T-Type Three-Level Invertersbased on a Circuit Level Decoupling Modulation

    DEFF Research Database (Denmark)

    Zhang, Zhe; Anthon, Alexander; Andersen, Michael A. E.

    2014-01-01

    frequencyincreases due to high switching loss of the equipped high voltagepower switches. In order to reduce switching loss and herebyenhance efficiency, a newly proposed circuit-level decouplingmodulation (CLDM) scheme is applied for these two widely usedthree-phase three-level inverters, as well...

  5. Positive and negative early life experiences differentially modulate long term survival and amyloid protein levels in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Lesuis, Sylvie L; Maurin, Herve; Borghgraef, Peter; Lucassen, Paul J; Van Leuven, Fred; Krugers, Harm J

    2016-06-28

    Stress has been implicated as a risk factor for the severity and progression of sporadic Alzheimer's disease (AD). Early life experiences determine stress responsivity in later life, and modulate age-dependent cognitive decline. Therefore, we examined whether early life experiences influence AD outcome in a bigenic mouse model which progressively develops combined tau and amyloid pathology (biAT mice).Mice were subjected to either early life stress (ELS) or to 'positive' early handling (EH) postnatally (from day 2 to 9). In biAT mice, ELS significantly compromised long term survival, in contrast to EH which increased life expectancy. In 4 month old mice, ELS-reared biAT mice displayed increased hippocampal Aβ levels, while these levels were reduced in EH-reared biAT mice. No effects of ELS or EH were observed on the brain levels of APP, protein tau, or PSD-95. Dendritic morphology was moderately affected after ELS and EH in the amygdala and medial prefrontal cortex, while object recognition memory and open field performance were not affected. We conclude that despite the strong transgenic background, early life experiences significantly modulate the life expectancy of biAT mice. Parallel changes in hippocampal Aβ levels were evident, without affecting cognition of young adult biAT mice.

  6. Modulation of the Pyrococcus abyssi NucS endonuclease activity by replication clamp at functional and structural levels.

    Science.gov (United States)

    Creze, Christophe; Ligabue, Alessio; Laurent, Sébastien; Lestini, Roxane; Laptenok, Sergey P; Khun, Joelle; Vos, Marten H; Czjzek, Mirjam; Myllykallio, Hannu; Flament, Didier

    2012-05-04

    Pyrococcus abyssi NucS is the founding member of a new family of structure-specific DNA endonucleases that interact with the replication clamp proliferating cell nuclear antigen (PCNA). Using a combination of small angle x-ray scattering and surface plasmon resonance analyses, we demonstrate the formation of a stable complex in solution, in which one molecule of the PabNucS homodimer binds to the outside surface of the PabPCNA homotrimer. Using fluorescent labels, PCNA is shown to increase the binding affinity of NucS toward single-strand/double-strand junctions on 5' and 3' flaps, as well as to modulate the cleavage specificity on the branched DNA structures. Our results indicate that the presence of a single major contact between the PabNucS and PabPCNA proteins, together with the complex-induced DNA bending, facilitate conformational flexibility required for specific cleavage at the single-strand/double-strand DNA junction.

  7. The Evidence for the Spread and Seeding Capacities of the Mutant Huntingtin Protein in in Vitro Systems and Their Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Maria Masnata

    2017-11-01

    Full Text Available Neurodegenerative disorders are not only characterized by specific patterns of cell loss but the presence and accumulation of various pathological proteins—both of which correlate with disease evolution. There is now mounting evidence to suggest that these pathological proteins present with toxic, at times prion-like, properties and can therefore seed pathology in neighboring as well remotely connected healthy neurons as they spread across the brain. What is less clear, at this stage, is how much this actually contributes to, and drives, the core pathogenic events. In this review, we present a comprehensive, up-to-date summary of the reported in vitro studies that support the spreading and seeding capacities of pathological proteins, with an emphasis on mutant huntingtin protein in the context of Huntington's disease, although in vivo work remains to be performed to validate this theory in this particular disease. We have further reviewed these findings in light of their potential implications for the development of novel therapeutic approaches.

  8. Highly dissipative Hénon map behavior in the four-level model of the CO 2 laser with modulated losses

    Science.gov (United States)

    Pando L., C. L.; Acosta, G. A. Luna; Meucci, R.; Ciofini, M.

    1995-02-01

    We show that the four-level model for the CO 2 laser with modulated losses behaves in a qualitatively similar way as the highly dissipative Hénon map. The ubiquity of elements of the universal sequence, their related symbolic dynamics, and the presence of reverse bifurcations of chaotic bands in the model are reminiscent of the logistic map which is the limit of the Hénon map when the Jacobian equals zero. The coexistence of attractors, its dynamics related to contraction of volumes in phase space and the associated return maps can be correlated with those of the highly dissipative Hénon map.

  9. Loss and thermal redistributed modulation methods for three-level neutral-point-clamped wind power inverter undergoing Low Voltage Ride Through

    DEFF Research Database (Denmark)

    Ma, Ke; Blaabjerg, Frede

    2012-01-01

    The three-level neutral-point-clamped (3L-NPC) converter is a promising multilevel topology in the application of mega-watts wind power generation system. However, the growing requirements by grid codes may impose high stress and even give reliability problem to this converter topology. This paper...... modulation methods, the thermal distribution in the 3L-NPC wind power inverter undergoing LVRT becomes more equal, and the junction temperature of the most stressed devices can be also relieved. Also the control ability of DC-bus neutral point potential, which is one of the crucial considerations for the 3L...

  10. Fashion Merchandising Module. An Advanced-Level Option for Distribution and Marketing. For the U.S.O.E. Occupational Cluster of 04.02 Apparel and Accessories Marketing.

    Science.gov (United States)

    Clis, Pat; And Others

    This instructional module on fashion merchandising is designed as a guide for secondary education teachers who are helping twelfth grade students develop occupational competency for entry-level positions in fashion-related jobs. An introductory section covers module goals, career opportunities and employment demands, administrative considerations,…

  11. Tumor-promoting phorbol ester transiently down-modulates the p53 level and blocks the cell cycle

    DEFF Research Database (Denmark)

    Skouv, J.; Jensen, P O; Forchhammer, J

    1994-01-01

    Activation of the protein kinase C signaling pathway by tumor-promoting phorbol esters, such as 4 beta-phorbol 12-myristate 13-acetate (PMA), induced a decrease in the level of p53 mRNA in several serum-starved human cell lines. Also, the tumor-promoting phosphatase inhibitor okadaic acid induced...... a decrease in the p53 mRNA level in the cell lines. Normal diploid as well as various tumor cell lines were tested. Two tumor cell lines, HeLa and A549, both containing the wild-type p53 gene, but very different levels of p53 protein, were studied in detail. In both cell lines, the level of p53 m......RNA was minimal after 9 h of exposure to PMA. After approximately 120 h, the p53 mRNA level was similar to the pretreatment level. PMA induced a similar transient decrease in the level of p53 protein in the A549 cell line. The decrease in the p53 mRNA level could not be explained by changes in the transcriptional...

  12. Mechanism for iron control of the Vibrio fischeri luminescence system: involvement of cyclic AMP and cyclic AMP receptor protein and modulation of DNA level.

    Science.gov (United States)

    Dunlap, P V

    1992-07-01

    Iron controls luminescence in Vibrio fischeri by an indirect but undefined mechanism. To gain insight into that mechanism, the involvement of cyclic AMP (cAMP) and cAMP receptor protein (CRP) and of modulation of DNA levels in iron control of luminescence were examined in V. fischeri and in Escherichia coli containing the cloned V. fischeri lux genes on plasmids. For V. fischeri and E. coli adenylate cyclase (cya) and CRP (crp) mutants containing intact lux genes (luxR luxICDABEG), presence of the iron chelator ethylenediamine-di(o-hydroxyphenyl acetic acid) (EDDHA) increased expression of the luminescence system like in the parent strains only in the cya mutants in the presence of added cAMP. In the E. coli strains containing a plasmid with a Mu dl(lacZ) fusion in luxR, levels of beta-galactosidase activity (expression from the luxR promoter) and luciferase activity (expression from the lux operon promoter) were both 2-3-fold higher in the presence of EDDHA in the parent strain, and for the mutants this response to EDDHA was observed only in the cya mutant in the presence of added cAMP. Therefore, cAMP and CRP are required for the iron restriction effect on luminescence, and their involvement in iron control apparently is distinct from the known differential control of transcription from the luxR and luxICDABEG promoters by cAMP-CRP. Furthermore, plasmid and chromosomal DNA levels were higher in E. coli and V. fischeri in the presence of EDDHA. The higher DNA levels correlated with an increase in expression of chromosomally encoded beta-galactosidase in E. coli and with a higher level of autoinducer in cultures of V. fischeri. These results implicate cAMP-CRP and modulation of DNA levels in the mechanism of iron control of the V. fischeri luminescence system.

  13. Modulation of the Pyrococcus abyssi NucS Endonuclease Activity by Replication Clamp at Functional and Structural Levels*

    Science.gov (United States)

    Creze, Christophe; Ligabue, Alessio; Laurent, Sébastien; Lestini, Roxane; Laptenok, Sergey P.; Khun, Joelle; Vos, Marten H.; Czjzek, Mirjam; Myllykallio, Hannu; Flament, Didier

    2012-01-01

    Pyrococcus abyssi NucS is the founding member of a new family of structure-specific DNA endonucleases that interact with the replication clamp proliferating cell nuclear antigen (PCNA). Using a combination of small angle x-ray scattering and surface plasmon resonance analyses, we demonstrate the formation of a stable complex in solution, in which one molecule of the PabNucS homodimer binds to the outside surface of the PabPCNA homotrimer. Using fluorescent labels, PCNA is shown to increase the binding affinity of NucS toward single-strand/double-strand junctions on 5′ and 3′ flaps, as well as to modulate the cleavage specificity on the branched DNA structures. Our results indicate that the presence of a single major contact between the PabNucS and PabPCNA proteins, together with the complex-induced DNA bending, facilitate conformational flexibility required for specific cleavage at the single-strand/double-strand DNA junction. PMID:22431731

  14. Revealing molecular-level surface structure of amyloid fibrils in liquid by means of frequency modulation atomic force microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Fukuma, Takeshi [Frontier Science Organization, Kanazawa University, Kakuma-machi, Kanazawa 920-1192 (Japan); Mostaert, Anika S; Jarvis, Suzanne P [Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Republic of Ireland (Ireland); Serpell, Louise C [Department of Biochemistry, University of Sussex, John Maynard Building, Falmer BN1 9QG (United Kingdom)], E-mail: fukuma@staff.kanazawa-u.ac.jp, E-mail: Anika.Mostaert@ucd.ie, E-mail: L.C.Serpell@sussex.ac.uk, E-mail: Suzi.Jarvis@ucd.ie

    2008-09-24

    We have investigated the surface structure of islet amyloid polypeptide (IAPP) fibrils and {alpha}-synuclein protofibrils in liquid by means of frequency modulation atomic force microscopy (FM-AFM). Angstroem-resolution FM-AFM imaging of isolated macromolecules in liquid is demonstrated for the first time. Individual {beta}-strands aligned perpendicular to the fibril axis with a spacing of 0.5 nm are resolved in FM-AFM images, which confirms cross-{beta} structure of IAPP fibrils in real space. FM-AFM images also reveal the existence of 4 nm periodic domains along the axis of IAPP fibrils. Stripe features with 0.5 nm spacing are also found in images of {alpha}-synuclein protofibrils. However, in contrast to the case for IAPP fibrils, the stripes are oriented 30 deg. from the axis, suggesting the possibility of {beta}-strand alignment in protofibrils different from that in mature fibrils or the regular arrangement of thioflavin T molecules present during the fibril preparation aligned at the surface of the protofibrils.

  15. Revealing molecular-level surface structure of amyloid fibrils in liquid by means of frequency modulation atomic force microscopy

    International Nuclear Information System (INIS)

    Fukuma, Takeshi; Mostaert, Anika S; Jarvis, Suzanne P; Serpell, Louise C

    2008-01-01

    We have investigated the surface structure of islet amyloid polypeptide (IAPP) fibrils and α-synuclein protofibrils in liquid by means of frequency modulation atomic force microscopy (FM-AFM). Angstroem-resolution FM-AFM imaging of isolated macromolecules in liquid is demonstrated for the first time. Individual β-strands aligned perpendicular to the fibril axis with a spacing of 0.5 nm are resolved in FM-AFM images, which confirms cross-β structure of IAPP fibrils in real space. FM-AFM images also reveal the existence of 4 nm periodic domains along the axis of IAPP fibrils. Stripe features with 0.5 nm spacing are also found in images of α-synuclein protofibrils. However, in contrast to the case for IAPP fibrils, the stripes are oriented 30 deg. from the axis, suggesting the possibility of β-strand alignment in protofibrils different from that in mature fibrils or the regular arrangement of thioflavin T molecules present during the fibril preparation aligned at the surface of the protofibrils

  16. Subsecond Sensory Modulation of Serotonin Levels in a Primary Sensory Area and Its Relation to Ongoing Communication Behavior in a Weakly Electric Fish.

    Science.gov (United States)

    Fotowat, Haleh; Harvey-Girard, Erik; Cheer, Joseph F; Krahe, Rüdiger; Maler, Leonard

    2016-01-01

    Serotonergic neurons of the raphe nuclei of vertebrates project to most regions of the brain and are known to significantly affect sensory processing. The subsecond dynamics of sensory modulation of serotonin levels and its relation to behavior, however, remain unknown. We used fast-scan cyclic voltammetry to measure serotonin release in the electrosensory system of weakly electric fish, Apteronotus leptorhynchus . These fish use an electric organ to generate a quasi-sinusoidal electric field for communicating with conspecifics. In response to conspecific signals, they frequently produce signal modulations called chirps. We measured changes in serotonin concentration in the hindbrain electrosensory lobe (ELL) with a resolution of 0.1 s concurrently with chirping behavior evoked by mimics of conspecific electric signals. We show that serotonin release can occur phase locked to stimulus onset as well as spontaneously in the ELL region responsible for processing these signals. Intense auditory stimuli, on the other hand, do not modulate serotonin levels in this region, suggesting modality specificity. We found no significant correlation between serotonin release and chirp production on a trial-by-trial basis. However, on average, in the trials where the fish chirped, there was a reduction in serotonin release in response to stimuli mimicking similar-sized same-sex conspecifics. We hypothesize that the serotonergic system is part of an intricate sensory-motor loop: serotonin release in a sensory area is triggered by sensory input, giving rise to motor output, which can in turn affect serotonin release at the timescale of the ongoing sensory experience and in a context-dependent manner.

  17. Electrically induced contraction levels of the quadriceps femoris muscles in healthy men: the effects of three patterns of burst-modulated alternating current and volitional muscle fatigue.

    Science.gov (United States)

    Parker, Michael G; Broughton, Alex J; Larsen, Ben R; Dinius, Josh W; Cimbura, Mac J; Davis, Matthew

    2011-12-01

    The purpose of this study was to compare electrically induced contraction levels produced by three patterns of alternating current in fatigued and nonfatigued skeletal muscles. Eighteen male volunteers without health conditions, with a mean (SD) age of 24.9 (3.4) yrs were randomly exposed to a fatiguing volitional isometric quadriceps contraction and one of three patterns of 2.5-KHz alternating current; two were modulated at 50 bursts per second (10% burst duty cycle with five cycles per burst and 90% burst duty cycle with 45 cycles per burst), and one pattern was modulated at 100 bursts per second (10% burst duty cycle with 2.5 cycles per burst). The electrically induced contraction levels produced by the three patterns of electrical stimulation were compared before and after the fatiguing contraction. The 10% burst duty cycles produced 42.9% (95% confidence interval, 29.1%-56.7%) and 32.1% (95% confidence interval, 18.2%-45.9%) more muscle force (P stronger muscle contractions. Furthermore, the stimulation patterns had no influence on the difference in muscle force before and after the fatiguing quadriceps contraction. Consequently, for clinical applications in which high forces are desired, the patterns using the 10% burst duty cycle may be helpful.

  18. Genetic Variations of Circulating Adiponectin Levels Modulate Changes in Appetite in Response to Weight-Loss Diets.

    Science.gov (United States)

    Ma, Wenjie; Huang, Tao; Heianza, Yoriko; Wang, Tiange; Sun, Dianjianyi; Tong, Jenny; Williamson, Donald A; Bray, George A; Sacks, Frank M; Qi, Lu

    2017-01-01

    Adiponectin plays key roles in regulating appetite and food intake. To investigate interactions between the genetic risk score (GRS) for adiponectin levels and weight-loss diets varying in macronutrient intake on long-term changes in appetite and adiponectin levels. A GRS was calculated based on 5 adiponectin-associated variants in 692 overweight adults from the 2-year Preventing Overweight Using Novel Dietary Strategies trial. Repeated measurements of plasma adiponectin levels and appetite-related traits, including cravings, fullness, prospective consumption, and hunger. Dietary fat showed nominally significant interactions with the adiponectin GRS on changes in appetite score and prospective consumption from baseline to 6 months (P for interaction = 0.014 and 0.017, respectively) after adjusting for age, sex, ethnicity, baseline body mass index, and baseline respective outcome values. The GRS for lower adiponectin levels was associated with a greater decrease in appetite (P appetite and adiponectin levels to weight-loss diets varying in fat intake. Copyright © 2017 by the Endocrine Society

  19. Intensity-modulated radiotherapy in patients with locally advanced rectal cancer reduces volume of bowel treated to high dose levels

    International Nuclear Information System (INIS)

    Urbano, M. Teresa Guerrero; Henrys, Anthony J.; Adams, Elisabeth J.; Norman, Andrew R.; Bedford, James L.; Harrington, Kevin J.; Nutting, Christopher M.; Dearnaley, David P.; Tait, Diana M.

    2006-01-01

    Purpose: To investigate the potential for intensity-modulated radiotherapy (IMRT) to spare the bowel in rectal tumors. Methods and Materials: The targets (pelvic nodal and rectal volumes), bowel, and bladder were outlined in 5 patients. All had conventional, three-dimensional conformal RT and forward-planned multisegment three-field IMRT plans compared with inverse-planned simultaneous integrated boost nine-field equally spaced IMRT plans. Equally spaced seven-field and five-field and five-field, customized, segmented IMRT plans were also evaluated. Results: Ninety-five percent of the prescribed dose covered at least 95% of both planning target volumes using all but the conventional plan (mean primary and pelvic planning target volume receiving 95% of the prescribed dose was 32.8 ± 13.7 Gy and 23.7 ± 4.87 Gy, respectively), reflecting a significant lack of coverage. The three-field forward planned IMRT plans reduced the volume of bowel irradiated to 45 Gy and 50 Gy by 26% ± 16% and 42% ± 27% compared with three-dimensional conformal RT. Additional reductions to 69 ± 51 cm 3 to 45 Gy and 20 ± 21 cm 3 to 50 Gy were obtained with the nine-field equally spaced IMRT plans-64% ± 11% and 64% ± 20% reductions compared with three-dimensional conformal RT. Reducing the number of beams and customizing the angles for the five-field equally spaced IMRT plan did not significantly reduce bowel sparing. Conclusion: The bowel volume irradiated to 45 Gy and 50 Gy was significantly reduced with IMRT, which could potentially lead to less bowel toxicity. Reducing the number of beams did not reduce bowel sparing and the five-field customized segmented IMRT plan is a reasonable technique to be tested in clinical trials

  20. Modulation of digestive physiology and biochemistry in Mytilus californianus in response to feeding level acclimation and microhabitat

    Directory of Open Access Journals (Sweden)

    Kwasi M. Connor

    2016-09-01

    Full Text Available The intertidal mussel Mytilus californianus is a critical foundation species that is exposed to fluctuations in the environment along tidal- and wave-exposure gradients. We investigated feeding and digestion in mussels under laboratory conditions and across environmental gradients in the field. We assessed whether mussels adopt a rate-maximization (higher ingestion and lower assimilation or a yield-maximization acquisition (lower ingestion and higher assimilation strategy under laboratory conditions by measuring feeding physiology and digestive enzyme activities. We used digestive enzyme activity to define resource acquisition strategies in laboratory studies, then measured digestive enzyme activities in three microhabitats at the extreme ends of the tidal- and wave-exposure gradients within a stretch of shore (<20 m projected sea-ward. Our laboratory results indicated that mussels benefit from a high assimilation efficiency when food concentration is low and have a low assimilation efficiency when food concentration is high. Additionally, enzyme activities of carbohydrases amylase, laminarinase and cellulase were elevated when food concentration was high. The protease trypsin, however, did not increase with increasing food concentration. In field conditions, low-shore mussels surprisingly did not have high enzyme activities. Rather, high-shore mussels exhibited higher cellulase activities than low-shore mussels. Similarly, trypsin activity in the high-shore-wave-sheltered microhabitat was higher than that in high-shore-wave-exposed. As expected, mussels experienced increasing thermal stress as a function of reduced submergence from low to high shore and shelter from wave-splash. Our findings suggest that mussels compensate for limited feeding opportunities and thermal stress by modulating digestive enzyme activities.

  1. IP3 levels and their modulation FY fusicoccin measured by a novel [3H] IP3 binding assay

    International Nuclear Information System (INIS)

    Aducci, P.; Marra, M.

    1990-01-01

    A recently developed sensitive assay based on the binding reaction of IP3 to bovine adrenal preparations has been utilized for determining the level of endogenous inositol-1,4,5 trisphosphate (IP3) in maize roots and coleoptiles. The amount of IP3 found in these tissues ranges from 0.1 to 1.0 nmol g-1 fresh weight. Reproducible results were obtained with extracts of tissues from a same harvest, while they showed a 2-3 fold variation when different batches of plantlets were compared. The fungal phytotoxin fusicoccin (FC) known to affect several physiological processes in higher plants, increases the level of IP3 in coleoptiles. This observation suggests that IP3 might be involved in the transduction of the FC encoded signal from its receptors at the plasmalemma level to the cell machinery

  2. High-throughput screening for compounds that modulate the cellular c-di-GMP level in bacteria

    DEFF Research Database (Denmark)

    Groizeleau, Julie; Andersen, Jens Bo; Givskov, Michael

    2017-01-01

    . The secondary messenger c-di-GMP is a positive regulator of biofilm formation in many clinically relevant bacteria, and it is assumed that drugs that lower the intracellular level of c-di-GMP will force biofilm bacteria into a more treatable planktonic lifestyle. We describe a protocol for high......-throughput screening of chemical libraries for compounds that lower the c-di-GMP level in bacteria, and potentially can serve as lead compounds in the development of novel biofilm dismantling drugs....

  3. Interaction of a common painkiller piroxicam and copper-piroxicam with chromatin causes structural alterations accompanied by modulation at the epigenomic/genomic level.

    Science.gov (United States)

    Goswami, Sathi; Sanyal, Sulagna; Chakraborty, Payal; Das, Chandrima; Sarkar, Munna

    2017-08-01

    NSAIDs are the most common class of painkillers and anti-inflammatory agents. They also show other functions like chemoprevention and chemosuppression for which they act at the protein but not at the genome level since they are mostly anions at physiological pH, which prohibit their approach to the poly-anionic DNA. Complexing the drugs with bioactive metal obliterate their negative charge and allow them to bind to the DNA, thereby, opening the possibility of genome level interaction. To test this hypothesis, we present the interaction of a traditional NSAID, Piroxicam and its copper complex with core histone and chromatin. Spectroscopy, DLS, and SEM studies were applied to see the effect of the interaction on the structure of histone/chromatin. This was coupled with MTT assay, immunoblot analysis, confocal microscopy, micro array analysis and qRT-PCR. The interaction of Piroxicam and its copper complex with histone/chromatin results in structural alterations. Such structural alterations can have different biological manifestations, but to test our hypothesis, we have focused only on the accompanied modulations at the epigenomic/genomic level. The complex, showed alteration of key epigenetic signatures implicated in transcription in the global context, although Piroxicam caused no significant changes. We have correlated such alterations caused by the complex with the changes in global gene expression and validated the candidate gene expression alterations. Our results provide the proof of concept that DNA binding ability of the copper complexes of a traditional NSAID, opens up the possibility of modulations at the epigenomic/genomic level. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. The common P446L polymorphism in GCKR inversely modulates fasting glucose and triglyceride levels and reduces type 2 diabetes risk in the DESIR prospective general French population.

    Science.gov (United States)

    Vaxillaire, Martine; Cavalcanti-Proença, Christine; Dechaume, Aurélie; Tichet, Jean; Marre, Michel; Balkau, Beverley; Froguel, Philippe

    2008-08-01

    Hepatic glucokinase (GCK) is a key regulator of glucose storage and disposal in the liver, where its activity is competitively modulated, with respect to glucose, by binding to glucokinase regulatory protein (GCKR) in the presence of fructose 6-phosphate. Genome-wide association studies for type 2 diabetes identified GCKR as a potential locus for modulating triglyceride levels. We evaluated, in a general French population, the contribution of the GCKR rs1260326-P446L polymorphism to quantitative metabolic parameters and to dyslipidemia and hyperglycemia risk. Genotype effects of rs1260326 were studied in 4,833 participants from the prospective DESIR (Data from an Epidemiological Study on the Insulin Resistance syndrome) cohort both at inclusion and using the measurements at follow-up. The minor T-allele of rs1260326 was strongly associated with lower fasting glucose (-1.43% per T-allele; P = 8 x 10(-13)) and fasting insulin levels (-4.23%; P = 3 x 10(-7)), lower homeostasis model assessment of insulin resistance index (-5.69%; P = 1 x 10(-8)), and, conversely, higher triglyceride levels (3.41%; P = 1 x 10(-4)) during the 9-year study. These effects relate to a lower risk of hyperglycemia (odds ratio [OR] 0.79 [95% CI 0.70-0.88]; P = 4 x 10(-5)) and of incident cases during the study (hazard ratio [HR] 0.83 [0.74-0.95]; P = 0.005). Moreover, an additive effect of GCKR rs1260326(T) and GCK (-30G) alleles conferred lower fasting glycemia (P = 1 x 10(-13)), insulinemia (P = 5 x 10(-6)), and hyperglycemia risk (P = 1 x 10(-6)). GCKR-L446 carriers are protected against type 2 diabetes despite higher triglyceride levels and risk of dyslipidemia, which suggests a potential molecular mechanism by which these two components of the metabolic syndrome can be dissociated.

  5. Modulation of memory with septal injections of morphine and glucose: effects on extracellular glucose levels in the hippocampus.

    Science.gov (United States)

    McNay, Ewan C; Canal, Clinton E; Sherwin, Robert S; Gold, Paul E

    2006-02-28

    The concentration of glucose in the extracellular fluid (ECF) of the hippocampus decreases substantially during memory testing on a hippocampus-dependent memory task. Administration of exogenous glucose, which enhances task performance, prevents this decrease, suggesting a relationship between hippocampal glucose availability and memory performance. In the present experiment, spontaneous alternation performance and task-related changes in hippocampal ECF glucose were assessed in rats after intraseptal administration of morphine, which impairs memory on a spontaneous alternation task, and after co-administration of intraseptal glucose, which attenuates that impairment. Consistent with previous findings, spontaneous alternation testing resulted in a decrease in hippocampal ECF glucose levels in control rats. However, rats that received intraseptal morphine prior to testing showed memory impairments and an absence of the task-related decrease in hippocampal ECF glucose levels. Intraseptal co-administration of glucose with morphine attenuated the memory impairment, and ECF glucose levels in the hippocampus decreased in a manner comparable to that seen in control rats. These data suggest that fluctuations in hippocampal ECF glucose levels may be a marker of mnemonic processing and support the view that decreases in extracellular glucose during memory testing reflect increased glucose demand during memory processing.

  6. Elevating Endogenous GABA Levels with GAT-1 Blockade Modulates Evoked but Not Induced Responses in Human Visual Cortex

    Science.gov (United States)

    Muthukumaraswamy, Suresh D; Myers, Jim F M; Wilson, Sue J; Nutt, David J; Hamandi, Khalid; Lingford-Hughes, Anne; Singh, Krish D

    2013-01-01

    The electroencephalographic/magnetoencephalographic (EEG/MEG) signal is generated primarily by the summation of the postsynaptic currents of cortical principal cells. At a microcircuit level, these glutamatergic principal cells are reciprocally connected to GABAergic interneurons. Here we investigated the relative sensitivity of visual evoked and induced responses to altered levels of endogenous GABAergic inhibition. To do this, we pharmacologically manipulated the GABA system using tiagabine, which blocks the synaptic GABA transporter 1, and so increases endogenous GABA levels. In a single-blinded and placebo-controlled crossover study of 15 healthy participants, we administered either 15 mg of tiagabine or a placebo. We recorded whole-head MEG, while participants viewed a visual grating stimulus, before, 1, 3 and 5 h post tiagabine ingestion. Using beamformer source localization, we reconstructed responses from early visual cortices. Our results showed no change in either stimulus-induced gamma-band amplitude increases or stimulus-induced alpha amplitude decreases. However, the same data showed a 45% reduction in the evoked response component at ∼80 ms. These data demonstrate that, in early visual cortex the evoked response shows a greater sensitivity compared with induced oscillations to pharmacologically increased endogenous GABA levels. We suggest that previous studies correlating GABA concentrations as measured by magnetic resonance spectroscopy to gamma oscillation frequency may reflect underlying variations such as interneuron/inhibitory synapse density rather than functional synaptic GABA concentrations. PMID:23361120

  7. Cold induced changes of adenosine levels in common eelpout (Zoarces viviparus): a role in modulating cytochrome c oxidase expression.

    Science.gov (United States)

    Eckerle, L G; Lucassen, M; Hirse, T; Pörtner, H O

    2008-04-01

    Exposure of ectothermic organisms to variations in temperatures causes a transient mismatch between energy supply and demand, which needs to be compensated for during acclimation. Adenosine accumulation from ATP breakdown indicates such an imbalance and its reversal reflects a restoration of energy status. We monitored adenosine levels in blood serum and liver of common eelpout (Zoarces viviparus) during cold exposure in vivo. Furthermore, we tested its effect on the pattern of thermal acclimation in hepatocytes isolated from cold- (4 degrees C) versus warm- (11 degrees C) exposed fish. Adenosine levels increased during cold exposure in vivo and reached a transient maximum after 24 h in serum, but remained permanently elevated in liver. Whole animal cold acclimation induced a rise of liver citrate synthase activity by 44+/-15%, but left cytochrome c oxidase activity (COX) and RNA expression of the respective genes unchanged. Cold incubation of hepatocytes from warm-acclimated fish failed to cause an increase of mitochondrial enzyme activities despite increased COX4 mRNA levels. Conversely, warm acclimation of hepatocytes from cold-acclimated fish reduced both enzyme activities and COX2 and COX4 mRNA levels by 26-37%. Adenosine treatment of both warm- and cold-acclimated hepatocytes suppressed COX activities but activated COX mRNA expression. These effects were not receptor mediated. The present findings indicate that adenosine has the potential to regulate mitochondrial functioning in vivo, albeit the pathways resulting in the contrasting effects on expression and activity need to be identified.

  8. Electroacupuncture Modulates Reproductive Hormone Levels in Patients with Primary Ovarian Insufficiency: Results from a Prospective Observational Study

    Directory of Open Access Journals (Sweden)

    Kehua Zhou

    2013-01-01

    Full Text Available To investigate the effects of electroacupuncture (EA on serum FSH, E2, and LH levels, women with primary ovarian insufficiency (POI were treated with EA once a day, five times a week for the first four weeks and once every other day, three times a week, for the following two months, and then were followed up for three months. Serum E2, FSH, and LH levels were measured at baseline, at the end of treatment, and during followup. A total of 11 women with POI were included in this prospective consecutive case series study. Compared with baseline, patients’ serum E2 increased, FSH decreased, and LH decreased (P=0.002, 0.001, and 0.002, resp. after EA treatment, and these effects persisted during followup. With treatment, 10 patients resumed menstruation (10/11, 90.91%, whereas one patient remained amenorrhea. During followup, two patients, including the one with amenorrhea during treatment, reported absence of menstruation. Temporary pain occurred occasionally, and no other adverse events were found during treatment. The results suggest that EA could decrease serum FSH and LH levels and increase serum E2 level in women with POI with little or no side effects; however, further randomized control trials are needed.

  9. MAT2B promotes adipogenesis by modulating SAMe levels and activating AKT/ERK pathway during porcine intramuscular preadipocyte differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Cunzhen; Chen, Xiaochang; Wu, Wenjing; Wang, Wusu; Pang, Weijun; Yang, Gongshe, E-mail: gsyang999@hotmail.com

    2016-05-15

    Intramuscular fat (IMF) has been demonstrated as one of the crucial factors of livestock meat quality. The MAT2B protein with MAT2α catalyzes the formation of methyl donor S- adenosylmethionine (SAMe) to mediate cell metabolism including proliferation and apoptosis. However, the regulatory effect of MAT2B on IMF deposition is still unclear. In this study, the effect of MAT2B on adipogenesis and its potential mechanism during porcine intramuscular preadipocyte differentiation was studied. The results showed that overexpression of MAT2B promoted adipogenesis and significantly up-regulated the mRNA and protein levels of adipogenic marker genes including FASN, PPARγ and aP2, consistently, knockdown of MAT2B inhibited lipid accumulation and down-regulated the mRNA and protein levels of the above genes. Furthermore, flow cytometry and EdU-labeling assay indicated that MAT2B regulate adipogenesis was partly due to influence intracellular SAMe levels and further affect cell clonal expansion. Also, increased expression of MAT2B activated the phosphorylations of AKT and ERK1/2, whereas knockdown of MAT2B blocked AKT signaling and repressed the phosphorylation of ERK1/2. Moreover, the inhibitory effect of LY294002 (a specific PI3K inhibitor) on the activities of AKT and ERK1/2 was partially recovered by overexpression of MAT2B in porcine intramuscular adipocytes. Finally, Co-IP experiments showed that MAT2B can directly interact with AKT. Taken together, our findings suggested that MAT2B acted as a positive regulator through modifying SAMe levels as well as activating AKT/ERK signaling pathway to promote porcine intramuscular adipocyte differentiation. - Highlights: • MAT2B up-regulates the expression of adipogenic marker genes and promotes porcine intramuscular preadipocyte differentiation. • MAT2B influences intracellular SAMe levels and further affects cell clonal expansion. • MAT2B interacts with AKT and activates AKT/ERK signaling pathway.

  10. APPLICATION OF ROUGH SET THEORY TO MAINTENANCE LEVEL DECISION-MAKING FOR AERO-ENGINE MODULES BASED ON INCREMENTAL KNOWLEDGE LEARNING

    Institute of Scientific and Technical Information of China (English)

    陆晓华; 左洪福; 蔡景

    2013-01-01

    The maintenance of an aero-engine usually includes three levels ,and the maintenance cost and period greatly differ depending on the different maintenance levels .To plan a reasonable maintenance budget program , airlines would like to predict the maintenance level of aero-engine before repairing in terms of performance parame-ters ,which can provide more economic benefits .The maintenance level decision rules are mined using the histori-cal maintenance data of a civil aero-engine based on the rough set theory ,and a variety of possible models of upda-ting rules produced by newly increased maintenance cases added to the historical maintenance case database are in-vestigated by the means of incremental machine learning .The continuously updated rules can provide reasonable guidance suggestions for engineers and decision support for planning a maintenance budget program before repai-ring .The results of an example show that the decision rules become more typical and robust ,and they are more accurate to predict the maintenance level of an aero-engine module as the maintenance data increase ,which illus-trates the feasibility of the represented method .

  11. Force and Directional Force Modulation Effects on Accuracy and Variability in Low-Level Pinch Force Tracking.

    Science.gov (United States)

    Park, Sangsoo; Spirduso, Waneen; Eakin, Tim; Abraham, Lawrence

    2018-01-01

    The authors investigated how varying the required low-level forces and the direction of force change affect accuracy and variability of force production in a cyclic isometric pinch force tracking task. Eighteen healthy right-handed adult volunteers performed the tracking task over 3 different force ranges. Root mean square error and coefficient of variation were higher at lower force levels and during minimum reversals compared with maximum reversals. Overall, the thumb showed greater root mean square error and coefficient of variation scores than did the index finger during maximum reversals, but not during minimum reversals. The observed impaired performance during minimum reversals might originate from history-dependent mechanisms of force production and highly coupled 2-digit performance.

  12. The efficacy of self-directed modules for clinical learning: advanced competencies in entry-level physical therapy education.

    Science.gov (United States)

    Peck, Kirk; Paschal, Karen; Black, Lisa; Nelson, Kelly

    2014-01-01

    Prior to graduation, students often express an interest to advance clinical and professional skills in teaching, research, administration, and various niche practice areas. The acquisition of advanced education in selected areas of practice is believed to improve employment opportunities, accelerate career advancement including eligibility for professional certifications, and contribute to personal satisfaction in the profession. The purpose of this paper is to (1) describe an innovative model of education, the Directed Practice Experience (DPE) elective, that incorporates a student-initiated learning process designed to achieve student-identified professional goals, and (2) report the outcomes for graduates who have completed the DPE in an entry-level program in physical therapy education. Students who met select criteria were eligible to complete a DPE. Applicants designed a 4- to 6-week clinical education experience consisting of stated rationale for personal and professional growth, examples of leadership and service, and self-directed objectives that are beyond entry-level expectations as measured by the revised Physical Therapist Clinical Performance Instrument, version 2006. Twenty-six students have completed DPEs since 2005. Fifty percent resulted in new academic partnerships. At least 25% of graduates now serve as clinical instructors for the entry-level program. Those who participated in DPEs have also completed post-graduate residencies, attained ABPTS Board certifications, authored peer-reviewed publications, and taught in both PT and residency programs. The DPE model allows qualified students to acquire advanced personal skills and knowledge prior to graduation in areas of professional practice that exceed entry-level expectations. The model is applicable to all CAPTE accredited physical therapy education programs and is especially beneficial for academic programs desiring to form new community partnerships for student clinical education.

  13. Down-Regulation of Neuropathy Target Esterase in Preeclampsia Placenta Inhibits Human Trophoblast Cell Invasion via Modulating MMP-9 Levels

    Directory of Open Access Journals (Sweden)

    Ting Zhong

    2018-02-01

    Full Text Available Background/Aims: Neuropathy target esterase (NTE, also known as neurotoxic esterase is proven to deacylate phosphatidylcholine (PC to glycerophosphocholine as a phospholipase B. Recently; studies showed that artificial phosphatidylserine/PC microvesicles can induce preeclampsia (PE-like changes in pregnant mice. However, it is unclear whether NTE plays a key role in the pathology of PE, a pregnancy-related disease, which was characterized by deficient trophoblast invasion and reduced trophoblast-mediated remodeling of spiral arteries. The aim of this study was to investigate the expression pattern of NTE in the placenta from women with PE and normal pregnancy, and the molecular mechanism of NTE involved in the development of PE. Methods: NTE expression levels in placentas from 20 pregnant women with PE and 20 healthy pregnant women were detected using quantitative PCR and immunohistochemistry staining. The effect of NTE on trophoblast migration and invasion and the underlying mechanisms were examined in HTR-8/SVneo cell lines by transfection method. Results: NTE mRNA and protein expression levels were significantly decreased in preeclamptic placentas than normal control. Over-expression of NTE in HTR-8/SVneo cells significantly promoted trophoblast cells migration and invasion and was associated with increased MMP-9 levels. Conversely, shRNA-mediated down-regulation of NTE markedly inhibited the cell migration and invasion. In addition, silencing NTE reduced the MMP-9 activity and phosphorylated Erk1/2 and AKT levels. Conclusions: Our results suggest that the decreased NTE may contribute to the development of PE through impairing trophoblast invasion by down-regulating MMP-9 via the Erk1/2 and AKT signaling pathway.

  14. Modulation of Extreme Flood Levels by Impoundment Significantly Offset by Floodplain Loss Downstream of the Three Gorges Dam

    Science.gov (United States)

    Mei, Xuefei; Dai, Zhijun; Darby, Stephen E.; Gao, Shu; Wang, Jie; Jiang, Weiguo

    2018-04-01

    River flooding—the world's most significant natural hazard—is likely to increase under anthropogenic climate change. Most large rivers have been regulated by damming, but the extent to which these impoundments can mitigate extreme flooding remains uncertain. Here the catastrophic 2016 flood on the Changjiang River is first analyzed to assess the effects of both the Changjiang's reservoir cascade and the Three Gorges Dam (TGD), the world's largest hydraulic engineering project on downstream flood discharge and water levels. We show that the Changjiang's reservoir cascade impounded over 30.0 × 103 m3/s of flow at the peak of the flood on 25 July 2016, preventing the occurrence of what would otherwise have been the second largest flood ever recorded in the reach downstream of the TGD. Half of this flood water storage was retained by the TGD alone, meaning that impoundment by the TGD reduced peak water levels at the Datong hydrometric station (on 25 July) by 1.47 m, compared to pre-TGD conditions. However, downstream morphological changes, in particular, extensive erosion of the natural floodplain, offset this reduction in water level by 0.22 m, so that the full beneficial impact of floodwater retention by the TGD was not fully realized. Our results highlight how morphological adjustments downstream of large dams may inhibit their full potential to mitigate extreme flood risk.

  15. Right hemisphere dominance directly predicts both baseline V1 cortical excitability and the degree of top-down modulation exerted over low-level brain structures.

    Science.gov (United States)

    Arshad, Q; Siddiqui, S; Ramachandran, S; Goga, U; Bonsu, A; Patel, M; Roberts, R E; Nigmatullina, Y; Malhotra, P; Bronstein, A M

    2015-12-17

    Right hemisphere dominance for visuo-spatial attention is characteristically observed in most right-handed individuals. This dominance has been attributed to both an anatomically larger right fronto-parietal network and the existence of asymmetric parietal interhemispheric connections. Previously it has been demonstrated that interhemispheric conflict, which induces left hemisphere inhibition, results in the modulation of both (i) the excitability of the early visual cortex (V1) and (ii) the brainstem-mediated vestibular-ocular reflex (VOR) via top-down control mechanisms. However to date, it remains unknown whether the degree of an individual's right hemisphere dominance for visuospatial function can influence, (i) the baseline excitability of the visual cortex and (ii) the extent to which the right hemisphere can exert top-down modulation. We directly tested this by correlating line bisection error (or pseudoneglect), taken as a measure of right hemisphere dominance, with both (i) visual cortical excitability measured using phosphene perception elicited via single-pulse occipital trans-cranial magnetic stimulation (TMS) and (ii) the degree of trans-cranial direct current stimulation (tDCS)-mediated VOR suppression, following left hemisphere inhibition. We found that those individuals with greater right hemisphere dominance had a less excitable early visual cortex at baseline and demonstrated a greater degree of vestibular nystagmus suppression following left hemisphere cathodal tDCS. To conclude, our results provide the first demonstration that individual differences in right hemisphere dominance can directly predict both the baseline excitability of low-level brain structures and the degree of top-down modulation exerted over them. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. A series of N-terminal epitope tagged Hdh knock-in alleles expressing normal and mutant huntingtin: their application to understanding the effect of increasing the length of normal huntingtin’s polyglutamine stretch on CAG140 mouse model pathogenesis

    Directory of Open Access Journals (Sweden)

    Zheng Shuqiu

    2012-08-01

    Full Text Available Abstract Background Huntington’s disease (HD is an autosomal dominant neurodegenerative disease that is caused by the expansion of a polyglutamine (polyQ stretch within Huntingtin (htt, the protein product of the HD gene. Although studies in vitro have suggested that the mutant htt can act in a potentially dominant negative fashion by sequestering wild-type htt into insoluble protein aggregates, the role of the length of the normal htt polyQ stretch, and the adjacent proline-rich region (PRR in modulating HD mouse model pathogenesis is currently unknown. Results We describe the generation and characterization of a series of knock-in HD mouse models that express versions of the mouse HD gene (Hdh encoding N-terminal hemaglutinin (HA or 3xFlag epitope tagged full-length htt with different polyQ lengths (HA7Q-, 3xFlag7Q-, 3xFlag20Q-, and 3xFlag140Q-htt and substitution of the adjacent mouse PRR with the human PRR (3xFlag20Q- and 3xFlag140Q-htt. Using co-immunoprecipitation and immunohistochemistry analyses, we detect no significant interaction between soluble full-length normal 7Q- htt and mutant (140Q htt, but we do observe N-terminal fragments of epitope-tagged normal htt in mutant htt aggregates. When the sequences encoding normal mouse htt’s polyQ stretch and PRR are replaced with non-pathogenic human sequence in mice also expressing 140Q-htt, aggregation foci within the striatum, and the mean size of htt inclusions are increased, along with an increase in striatal lipofuscin and gliosis. Conclusion In mice, soluble full-length normal and mutant htt are predominantly monomeric. In heterozygous knock-in HD mouse models, substituting the normal mouse polyQ and PRR with normal human sequence can exacerbate some neuropathological phenotypes.

  17. Regional evidence of modulation of cardiac adiponectin level in dilated cardiomyopathy: pilot study in a porcine animal model

    Directory of Open Access Journals (Sweden)

    Caselli Chiara

    2012-11-01

    Full Text Available Abstract Background The role of systemic and myocardial adiponectin (ADN in dilated cardiomyopathy is still debated. We tested the regulation of both systemic and myocardial ADN and the relationship with AMP-activated protein kinase (AMPK activity in a swine model of non-ischemic dilated cardiomyopathy. Methods and results Cardiac tissue was collected from seven instrumented adult male minipigs by pacing the left ventricular (LV free wall (180 beats/min, 3 weeks, both from pacing (PS and opposite sites (OS, and from five controls. Circulating ADN levels were inversely related to global and regional cardiac function. Myocardial ADN in PS was down-regulated compared to control (p Conclusions Paradoxically, circulating ADN did not show any cardioprotective effect, confirming its role as negative prognostic biomarker of heart failure. Myocardial ADN was reduced in PS compared to control in an AMPK-independent fashion, suggesting the occurrence of novel mechanisms by which reduced cardiac ADN levels may regionally mediate the decline of cardiac function.

  18. Nicotinamidase modulation of NAD+ biosynthesis and nicotinamide levels separately affect reproductive development and cell survival in C. elegans.

    Science.gov (United States)

    Vrablik, Tracy L; Huang, Li; Lange, Stephanie E; Hanna-Rose, Wendy

    2009-11-01

    Nicotinamide adenine dinucleotide (NAD(+)) is a central molecule in cellular metabolism and an obligate co-substrate for NAD(+)-consuming enzymes, which regulate key biological processes such as longevity and stress responses. Although NAD(+) biosynthesis has been intensely studied, little analysis has been done in developmental models. We have uncovered novel developmental roles for a nicotinamidase (PNC), the first enzyme in the NAD(+) salvage pathway of invertebrates. Mutations in the Caenorhabditis elegans nicotinamidase PNC-1 cause developmental and functional defects in the reproductive system; the development of the gonad is delayed, four uterine cells die by necrosis and the mutant animals are egg-laying defective. The temporal delay in gonad development results from depletion of the salvage pathway product NAD(+), whereas the uv1 cell necrosis and egg-laying defects result from accumulation of the substrate nicotinamide. Thus, regulation of both substrate and product level is key to the biological activity of PNC-1. We also find that diet probably affects the levels of these metabolites, as it affects phenotypes. Finally, we identified a secreted isoform of PNC-1 and confirmed its extracellular localization and functional activity in vivo. We demonstrate that nicotinamide phosphoribosyltransferase (Nampt), the equivalent enzyme in nicotinamide recycling to NAD(+) in vertebrates, can functionally substitute for PNC-1. As Nampt is also secreted, we postulate an evolutionarily conserved extracellular role for NAD(+) biosynthetic enzymes during development and physiology.

  19. Modulation of DNA methylation levels sensitizes doxorubicin-resistant breast adenocarcinoma cells to radiation-induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Luzhna, Lidia [Department of Biological Sciences, University of Lethbridge, AB, Canada T1K 3M4 (Canada); Kovalchuk, Olga, E-mail: olga.kovalchuk@uleth.ca [Department of Biological Sciences, University of Lethbridge, AB, Canada T1K 3M4 (Canada)

    2010-02-05

    Chemoresistant tumors often fail to respond to other cytotoxic treatments such as radiation therapy. The mechanisms of chemo- and radiotherapy cross resistance are not fully understood and are believed to be epigenetic in nature. We hypothesize that MCF-7 cells and their doxorubicin-resistant variant MCF-7/DOX cells may exhibit different responses to ionizing radiation due to their dissimilar epigenetic status. Similar to previous studies, we found that MCF-7/DOX cells harbor much lower levels of global DNA methylation than MCF-7 cells. Furthermore, we found that MCF-7/DOX cells had lower background apoptosis levels and were less responsive to radiation than MCF-7 cells. Decreased radiation responsiveness correlated to significant global DNA hypomethylation in MCF-7/DOX cells. Here, for the first time, we show that the radiation resistance of MCF-7/DOX cells can be reversed by an epigenetic treatment - the application of methyl-donor SAM. SAM-mediated reversal of DNA methylation led to elevated radiation sensitivity in MCF-7/DOX cells. Contrarily, application of SAM on the radiation sensitive and higher methylated MCF-7 cells resulted in a decrease in their radiation responsiveness. This data suggests that a fine balance of DNA methylation is needed to insure proper radiation and drug responsiveness.

  20. Short-term exposure to the organotin compound triphenyltin modulates esterified steroid levels in females of Marisa cornuarietis.

    Science.gov (United States)

    Lyssimachou, Angeliki; Bachmann, J; Porte, C

    2008-08-29

    Long-term exposures to organotin compounds have shown alterations on endogenous steroid levels in gastropods together with the development of imposex. However, information regarding short-term effects of these compounds on the endocrine system of gastropods is lacking. This work aimed at investigating those responses in the ramshorn snail Marisa cornuarietis by looking at both endogenous levels of free and esterified steroids and the metabolism of the androgen precursor androstenedione by digestive gland/gonad microsomal fractions. One-week exposure to the organotin compound triphenyltin (TPT) led to a significant increase in esterified testosterone (60-85%) and a decrease in esterified estradiol (50-84%) in females, but had no effect on males. The observed alterations in esterified steroids were not directly related to changes in P450 aromatase activity that remained unchanged in exposed females. The enzymes involved in the metabolism of the androgen precursor androstenedione, namely 17beta-hydroxysteroid dehydrogenases and 5alpha-reductases, were not significantly altered by TPT exposure, suggesting that such enzymes are not primary targets of TPT in M. cornuarietis. Additional studies are needed to fully understand the significance of the observed alterations in females and their potential relationship with the development of imposex.

  1. Representational momentum in dynamic facial expressions is modulated by the level of expressed pain: Amplitude and direction effects.

    Science.gov (United States)

    Prigent, Elise; Amorim, Michel-Ange; de Oliveira, Armando Mónica

    2018-01-01

    Humans have developed a specific capacity to rapidly perceive and anticipate other people's facial expressions so as to get an immediate impression of their emotional state of mind. We carried out two experiments to examine the perceptual and memory dynamics of facial expressions of pain. In the first experiment, we investigated how people estimate other people's levels of pain based on the perception of various dynamic facial expressions; these differ both in terms of the amount and intensity of activated action units. A second experiment used a representational momentum (RM) paradigm to study the emotional anticipation (memory bias) elicited by the same facial expressions of pain studied in Experiment 1. Our results highlighted the relationship between the level of perceived pain (in Experiment 1) and the direction and magnitude of memory bias (in Experiment 2): When perceived pain increases, the memory bias tends to be reduced (if positive) and ultimately becomes negative. Dynamic facial expressions of pain may reenact an "immediate perceptual history" in the perceiver before leading to an emotional anticipation of the agent's upcoming state. Thus, a subtle facial expression of pain (i.e., a low contraction around the eyes) that leads to a significant positive anticipation can be considered an adaptive process-one through which we can swiftly and involuntarily detect other people's pain.

  2. Huntingtin-Interacting Protein 1-Related Protein Plays a Critical Role in Dendritic Development and Excitatory Synapse Formation in Hippocampal Neurons

    Directory of Open Access Journals (Sweden)

    Lin Peng

    2017-06-01

    Full Text Available Huntingtin-interacting protein 1-related (HIP1R protein is considered to be an endocytic adaptor protein like the other two members of the Sla2 family, Sla2p and HIP1. They all contain homology domains responsible for the binding of clathrin, inositol lipids and F-actin. Previous studies have revealed that HIP1R is highly expressed in different regions of the mouse brain and localizes at synaptic structures. However, the function of HIP1R in the nervous system remains unknown. In this study, we investigated HIP1R function in cultured rat hippocampal neurons using an shRNA knockdown approach. We found that, after HIP1R knockdown, the dynamics and density of dendritic filopodia, and dendritic branching and complexity were significantly reduced in developing neurons, as well as the densities of dendritic spines and PSD95 clusters in mature neurons. Moreover, HIP1R deficiency led to significantly reduced expression of the ionotropic glutamate receptor GluA1, GluN2A and GluN2B subunits, but not the GABAA receptor α1 subunit. Similarly, HIP1R knockdown reduced the amplitude and frequency of the miniature excitatory postsynaptic current, but not of the miniature inhibitory postsynaptic current. In addition, the C-terminal proline-rich region of HIP1R responsible for cortactin binding was found to confer a dominant-negative effect on dendritic branching in cultured developing neurons, implying a critical role of cortactin binding in HIP1R function. Taken together, the results of our study suggest that HIP1R plays important roles in dendritic development and excitatory synapse formation and function.

  3. Collateral Resistance and Sensitivity Modulate Evolution of High-Level Resistance to Drug Combination Treatment in Staphylococcus aureus

    DEFF Research Database (Denmark)

    de Evgrafov, Mari Cristina Rodriguez; Gumpert, Heidi; Munck, Christian

    2015-01-01

    As drug-resistant pathogens continue to emerge, combination therapy will increasingly be relied upon to treat infections and to help combat further development of multidrug resistance. At present a dichotomy exists between clinical practice, which favors therapeutically synergistic combinations......, to reflect drug concentrations more likely to be encountered during treatment. We performed a series of adaptive evolution experiments using Staphylococcus aureus. Interestingly, no relationship between drug interaction type and resistance evolution was found as resistance increased significantly beyond wild......-type levels. All drug combinations, irrespective of interaction types, effectively limited resistance evolution compared with monotreatment. Cross-resistance and collateral sensitivity were found to be important factors in the extent of resistance evolution toward a combination. Comparative genomic analyses...

  4. Observational evidences on the modulation of the South American Low Level Jet east of the Andes according the ENSO variability

    Directory of Open Access Journals (Sweden)

    G. A. M. Silva

    2009-02-01

    Full Text Available The differences on the phase and wavelength of the quasi-stationary waves over the South America generated by El Niño (EN and La Niña (LN events seem to affect the daily evolution of the South American Low Level Jet east of the Andes (SALLJ. For the austral summer period of 1977–2004 the SALLJ episodes detected according to Bonner criterion 1 show normal to above-normal frequency in EN years, and in LN years the episodes show normal to below-normal frequency.

    During EN and LN years the SALLJ episodes were associated with positive rainfall anomalies over the La Plata Basin, but more intense during LN years. During EN years the increase in the SALLJ cases were associated to intensification of the Subtropical Jet (SJ around 30° S and positive Sea Level Pressure (SLP anomalies over the western equatorial Atlantic and tropical South America, particularly over central Brazil. This favored the intensification of the northeasterly trade winds over the northern continent and it channeled by the Andes mountain to the La Plata Basin region where negative SLP are found. The SALLJ cases identified during the LN events were weaker and less frequent when compared to those for EN years. In this case the SJ was weaker than in EN years and the negative SLP anomalies over the tropical continent contributed to the inversion of the northeasterly trade winds. Also a southerly flow anomaly was generated by the geostrophic balance due to the anomalous blocking over southeast Pacific and the intense cyclonic transient over the southern tip of South America. As result the warm tropical air brought by the SALLJ encounters the cold extratropical air from the southerly winds over the La Plata basin. This configuration can increase the conditional instability over the La Plata basin and may explain the more intense positive rainfall anomalies in SALLJ cases during LN years than in EN years.

  5. Salicylic acid modulates levels of phosphoinositide dependent-phospholipase C substrates and products to remodel the Arabidopsis suspension cell transcriptome

    Directory of Open Access Journals (Sweden)

    Eric eRuelland

    2014-11-01

    Full Text Available Basal phosphoinositide-dependent phospholipase C (PI-PLC activity controls gene expression in Arabidopsis suspension cells and seedlings. PI-PLC catalyzes the production of phosphorylated inositol and diacylglycerol (DAG from phosphoinositides. It is not known how PI-PLC regulates the transcriptome although the action of DAG-kinase (DGK on DAG immediately downstream from PI-PLC is responsible for some of the regulation. We previously established a list of genes whose expression is affected in the presence of PI-PLC inhibitors. Here this list of genes was used as a signature in similarity searches of curated plant hormone response transcriptome data. The strongest correlations obtained with the inhibited PI-PLC signature were with salicylic acid (SA treatments. We confirm here that in Arabidopsis suspension cells SA treatment leads to an increase in phosphoinositides, then demonstrate that SA leads to a significant 20% decrease in phosphatidic acid, indicative of a decrease in PI-PLC products. Previous sets of microarray data were re-assessed. The SA response of one set of genes was dependent on phosphoinositides. Alterations in the levels of a second set of genes, mostly SA-repressed genes, could be related to decreases in PI-PLC products that occur in response to SA action. Together, the two groups of genes comprise at least 40% of all SA-responsive genes. Overall these two groups of genes are distinct in the functional categories of the proteins they encode, their promoter cis-elements and their regulation by DGK or phospholipase D. SA-regulated genes dependent on phosphoinositides are typical SA response genes while those with an SA response that is possibly dependent on PI-PLC products are less SA-specific. We propose a model in which SA inhibits PI-PLC activity and alters levels of PI-PLC products and substrates, thereby regulating gene expression divergently.

  6. Perception of social networking benefits in the support of a PBL module according to students' performance levels.

    Science.gov (United States)

    Ekarattanawong, Sophapun; Thuppia, Amornnat; Chamod, Pholasit; Pattharanitima, Pattharawin; Suealek, Nuchanart; Rojpibulstit, Panadda

    2015-03-01

    The use ofsocial networking to all levels of medical teaching as a communication tool between instructors and students has drawn much interest and increased usage. As Facebook is one of the most popular social networking sites among students, a Facebook page has been used in the Genitourinary System problem-based learning (PBL) course at the Faculty of Medicine, Thammasat University in the year 2014. The objective of this work is to study the perception ofusing a Facebook page to support PBL in an integrated pre- clinical year course. The Genitourinary System course committee introduced Facebook page to the 2"d year medical students who enrolled and instructors involved in the course. At the beginning ofthe course, the objectives ofFacebook page setting were informed as follows: 1) public relations, 2) channelfor questions and responses to address curiosities between students and instructors, 3) learning stimulation and 4) supporting good relationship between course coordinators and students. The participants consisted of 177 students who voluntarily allowed their opinion to be used in analysis and dissemination after completing a questionnaire about using the Facebook page in PBL at the end. A Likert scale was used to determine satisfaction scores for nine questions. Finally, the mean satisfaction was compared for each question and for students with different academic performances (great, good, fine, weak). The students liked the page (averaged satisfaction score 4.64) and wanted it to continue to be used in coursework (4.63), especiallyfor students at mid-level when compared to students with great performances (psocial networking, particularly Facebook pages, achieved all the four the stated objectives. Since this was the first time social networking was applied, some of faculty members had concern that their personal information would be disseminated to the public. Moreover there was still minimal knowledge of sharing among students. The Facebook "closed group

  7. Importance of contouring the cervical spine levels in initial intensity-modulated radiation therapy radiation for head and neck cancers: Implications for re-irradiation

    Directory of Open Access Journals (Sweden)

    Parashar Bhupesh

    2009-01-01

    Full Text Available Aim: To evaluate the maximum differential cervical spinal (C-spine cord dose in intensity-modulated radiation therapy (IMRT plans of patients undergoing radiotherapy for treatment of head and neck cancer. Materials and Methods: The C-spine of ten head and neck cancer patients that were planned using IMRT and each cervical vertebral body and the right and left sides was contoured by splitting the cord in the center. Dose-volume histograms (DVH and maximum point doses were obtained for each contour and compared. Results: The dose to the cord varied with the location of the primary tumor but such variation was not consistently seen. This report provides information that is critical for planning reirradiation treatments. We recommend that contouring of the C-spine cord with IMRT should include outlining of each cervical cord level and identification of the right and the left sides of the cord on each plan.

  8. Design of electronic modules for the low-level RF systems at CERN. With particular regard to a new trigger unit for the Super Proton Synchrotron.

    CERN Document Server

    Levens, Thomas Edward; Knox, Andrew

    This report presents the work completed while the author was working for the BE-RF-FB group at the European Organization for Nuclear Research during the period of June to December 2010. The placement was completed as part of the University of Glasgow course ‘Industrial Project EE5’ which is requirement during the final year of the Degree of Master of Engineering. The report will pay particular attention to the hardware and firmware design of the ‘Dual Trigger Unit’, a new electronic module for the low-level RF system of the Super Proton Synchrotron accelerator which generates delayed timing pulses in order to trigger other hardware. In addition to this, the report will cover other projects completed during the period, including work on a prototype of the ‘VME Peak Detector’ card for the Large Hadron Collider beam observation system.

  9. NEU3 sialidase strictly modulates GM3 levels in skeletal myoblasts C2C12 thus favoring their differentiation and protecting them from apoptosis.

    Science.gov (United States)

    Anastasia, Luigi; Papini, Nadia; Colazzo, Francesca; Palazzolo, Giacomo; Tringali, Cristina; Dileo, Loredana; Piccoli, Marco; Conforti, Erika; Sitzia, Clementina; Monti, Eugenio; Sampaolesi, Maurilio; Tettamanti, Guido; Venerando, Bruno

    2008-12-26

    Membrane-bound sialidase NEU3, often referred to as the "ganglioside sialidase," has a critical regulatory function on the sialoglycosphingolipid pattern of the cell membrane, with an anti-apoptotic function, especially in cancer cells. Although other sialidases have been shown to be involved in skeletal muscle differentiation, the role of NEU3 had yet to be disclosed. Herein we report that NEU3 plays a key role in skeletal muscle differentiation by strictly modulating the ganglioside content of adjacent cells, with special regard to GM3. Induced down-regulation of NEU3 in murine C2C12 myoblasts, even when partial, totally inhibits their capability to differentiate by increasing the GM3 level above a critical point, which causes epidermal growth factor receptor inhibition (and ultimately its down-regulation) and an higher responsiveness of myoblasts to the apoptotic stimuli.

  10. Lactobacillus rhamnosus ATCC 7469 exopolysaccharides synergizes with low level ionizing radiation to modulate signaling molecular targets in colorectal carcinogenesis in rats.

    Science.gov (United States)

    Zahran, Walid E; Elsonbaty, Sawsan M; Moawed, Fatma S M

    2017-08-01

    Combination therapy that targets cellular signaling pathway represents an alternative therapy for the treatment of colon cancer (CRC). The present study was therefore aimed to investigate the probable interaction of Lactobacillus rhamnosus ATCC 7469 exopolysaccharides (EPS) with low level ionizing γ radiation (γ-R) exposure against dimethylhydrazine (DMH)- induced colorectal carcinogenesis in rats. Colon cancer was induced with 20mg DMH/kg BW. Rats received daily by gastric gavage 100mg EPS/Kg BW concomitant with 1Gy γ-R over two months. Colonic oxidative and inflammatory stresses were assessed. The change in the expression of p-p38 MAPK, p-STAT3, β-catenin, NF-kB, COX-2 and iNOS was evaluated by western blotting and q-PCR. It was found that DMH treatment significantly induced colon oxidative injury accompanied by inflammatory disturbance along with increased protein expression of the targeted signaling factors p-p38 MAPK, p-STAT3 and β-catenin. The mRNA gene expression of NF-kB, COX-2 and iNOS was significantly higher in DMH-treated animals. It's worthy to note that colon tissues with DMH treatment showed significant dysplasia and anaplasia of the glandular mucosal lining epithelium with loses of goblet cells formation, pleomorphism in the cells and hyperchromachia in nuclei. Interestingly, EPS treatment with γ-R exposure showed statistically significant amelioration of the oxidative and inflammatory biomarkers with modulated signaling molecular factors accompanied by improved histological structure against DMH-induced CRC. In conclusion, our findings showed that Lactobacillus rhamnosus ATCC 7469 EPS with low level γ-R in synergistic interaction are efficacious control against CRC progression throughout the modulation of key signaling growth factors associated with inflammation via antioxidant mediated anti-inflammatory and anti-proliferative activities. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Elevated Levels of Endocannabinoids in Chronic Hepatitis C May Modulate Cellular Immune Response and Hepatic Stellate Cell Activation

    Directory of Open Access Journals (Sweden)

    Eleonora Patsenker

    2015-03-01

    Full Text Available The endocannabinoid (EC system is implicated in many chronic liver diseases, including hepatitis C viral (HCV infection. Cannabis consumption is associated with fibrosis progression in patients with chronic hepatitis C (CHC, however, the role of ECs in the development of CHC has never been explored. To study this question, anandamide (AEA and 2-arachidonoyl glycerol (2-AG were quantified in samples of HCV patients and healthy controls by gas and liquid chromatography mass spectrometry. Fatty acid amide hydrolase (FAAH and monoaclyglycerol lipase (MAGL activity was assessed by [3H]AEA and [3H]2-AG hydrolysis, respectively. Gene expression and cytokine release were assayed by TaqMan PCR and ELISpot, respectively. AEA and 2-AG levels were increased in plasma of HCV patients, but not in liver tissues. Hepatic FAAH and MAGL activity was not changed. In peripheral blood mononuclear cells (PBMC, ECs inhibited IFN-γ, TNF-α, and IL-2 secretion. Inhibition of IL-2 by endogenous AEA was stronger in PBMC from HCV patients. In hepatocytes, 2-AG induced the expression of IL-6, -17A, -32 and COX-2, and enhanced activation of hepatic stellate cells (HSC co-cultivated with PBMC from subjects with CHC. In conclusion, ECs are increased in plasma of patients with CHC and might reveal immunosuppressive and profibrogenic effects.

  12. Diclofenac inhibits tumor growth in a murine model of pancreatic cancer by modulation of VEGF levels and arginase activity.

    Directory of Open Access Journals (Sweden)

    Nina Mayorek

    Full Text Available BACKGROUND: Diclofenac is one of the oldest anti-inflammatory drugs in use. In addition to its inhibition of cyclooxygenases (COX, diclofenac potently inhibits phospholipase A(2 (PLA(2, thus yielding a broad anti-inflammatory effect. Since inflammation is an important factor in the development of pancreatic tumors we explored the potential of diclofenac to inhibit tumor growth in mice inoculated with PANCO2 cells orthotopically. METHODOLOGY/PRINCIPAL FINDINGS: We found that diclofenac treatment (30 mg/kg/bw for 11 days of mice inoculated with PANC02 cells, reduced the tumor weight by 60%, correlating with increased apoptosis of tumor cells. Since this effect was not observed in vitro on cultured PANCO2 cells, we theorized that diclofenac beneficial treatment involved other mediators present in vivo. Indeed, diclofenac drastically decreased tumor vascularization by downregulating VEGF in the tumor and in abdominal cavity fluid. Furthermore, diclofenac directly inhibited vascular sprouting ex vivo. Surprisingly, in contrast to other COX-2 inhibitors, diclofenac increased arginase activity/arginase 1 protein content in tumor stroma cells, peritoneal macrophages and white blood cells by 2.4, 4.8 and 2 fold, respectively. We propose that the subsequent arginine depletion and decrease in NO levels, both in serum and peritoneal cavity, adds to tumor growth inhibition by malnourishment and poor vasculature development. CONCLUSION/SIGNIFICANCE: In conclusion, diclofenac shows pronounced antitumoral properties in pancreatic cancer model that can contribute to further treatment development. The ability of diclofenac to induce arginase activity in tumor stroma, peritoneal macrophages and white blood cells provides a tool to study a controversial issue of pro-and antitumoral effects of arginine depletion.

  13. Diclofenac inhibits tumor growth in a murine model of pancreatic cancer by modulation of VEGF levels and arginase activity.

    Science.gov (United States)

    Mayorek, Nina; Naftali-Shani, Nili; Grunewald, Myriam

    2010-09-15

    Diclofenac is one of the oldest anti-inflammatory drugs in use. In addition to its inhibition of cyclooxygenases (COX), diclofenac potently inhibits phospholipase A(2) (PLA(2)), thus yielding a broad anti-inflammatory effect. Since inflammation is an important factor in the development of pancreatic tumors we explored the potential of diclofenac to inhibit tumor growth in mice inoculated with PANCO2 cells orthotopically. We found that diclofenac treatment (30 mg/kg/bw for 11 days) of mice inoculated with PANC02 cells, reduced the tumor weight by 60%, correlating with increased apoptosis of tumor cells. Since this effect was not observed in vitro on cultured PANCO2 cells, we theorized that diclofenac beneficial treatment involved other mediators present in vivo. Indeed, diclofenac drastically decreased tumor vascularization by downregulating VEGF in the tumor and in abdominal cavity fluid. Furthermore, diclofenac directly inhibited vascular sprouting ex vivo. Surprisingly, in contrast to other COX-2 inhibitors, diclofenac increased arginase activity/arginase 1 protein content in tumor stroma cells, peritoneal macrophages and white blood cells by 2.4, 4.8 and 2 fold, respectively. We propose that the subsequent arginine depletion and decrease in NO levels, both in serum and peritoneal cavity, adds to tumor growth inhibition by malnourishment and poor vasculature development. In conclusion, diclofenac shows pronounced antitumoral properties in pancreatic cancer model that can contribute to further treatment development. The ability of diclofenac to induce arginase activity in tumor stroma, peritoneal macrophages and white blood cells provides a tool to study a controversial issue of pro-and antitumoral effects of arginine depletion.

  14. Polyphenols of Salix aegyptiaca modulate the activities of drug metabolizing and antioxidant enzymes, and level of lipid peroxidation.

    Science.gov (United States)

    Nauman, Mohd; Kale, R K; Singh, Rana P

    2018-03-07

    Salix aegyptiaca is known for its medicinal properties mainly due to the presence of salicylate compounds. However, it also contains other beneficial phytochemicals such as gallic acid, quercetin, rutin and vanillin. The aim of the study was to examine the redox potential, antioxidant and anti-inflammatory activity of these phytochemicals along with acetylsalicylic acid. The redox potential and antioxidant activity of gallic acid, quercetin, rutin, vanillin and acetylsalicylic acid were determined by oxidation-reduction potential electrode method and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, respectively. In ex vivo studies, antioxidant activity of these phytochemicals was determined by lipid peroxidation and carbonyl content assay in the liver of mice. Anti-inflammatory activity was determined by protein denaturation method. Six-week old C57BL/6 mice treated with gallic acid (100 mg/kg body weight) and acetylsalicylic acid (25 and 50 mg/kg body weight) to investigate their in vivo modulatory effects on the specific activities of drug metabolizing phase I and phase II enzymes, antioxidant enzymes and level of lipid peroxidation in liver. The order of ability to donate electron and antioxidant activity was found to be: gallic acid > quercetin > rutin > vanillin > acetylsalicylic acid. In ex vivo studies, the similar pattern and magnitude of inhibitory effects of these phytochemicals against peroxidative damage in microsomes and protein carbonyl in cytosolic fraction were observed. In in vivo studies, gallic acid and acetylsalicylic acid alone or in combination, enhanced the specific activities of drug metabolizing phase I and phase II enzymes as well as antioxidant enzymes and also inhibited lipid peroxidation in liver. These findings show a close link between the electron donation and antioxidation potential of these phytochemicals, and in turn their biological activity. Gallic acid, quercetin, rutin and vanillin were found to be better electron donors and

  15. Boronated protoporphyrin (BOPP): localization in lysosomes of the human glioma cell line SF-767 with uptake modulated by lipoprotein levels

    International Nuclear Information System (INIS)

    Callahan, Daniel E.; Forte, Trudy M.; Javed Afzal, S.M.; Deen, Dennis F.; Kahl, Stephen B.; Bjornstad, Kathleen A.; Bauer, William F.; Blakely, Eleanor A.

    1999-01-01

    concentrations of BOPP were randomly distributed throughout the cytoplasm; however, larger lysosomes containing BOPP were concentrated around the cell nucleus. Little or no BOPP accumulated in the cell nucleus. At incubation concentrations of 20 and 40 μg/ml (24-h time point), BOPP uptake in SF-767 cells was reduced in LPDS compared with NS (66% reduction). A similar result was observed for normal human fibroblasts (AG-1522 cells, 40 μg/ml, 24 h). At 40 μg/ml, in both NS and LPDS at 24 h, BOPP accumulation in LDL receptor-deficient human fibroblasts (GM019-15C cells) was reduced relative to AG-1522 cells. BOPP accumulation in GM019-15C cells (40 μg/ml, 24 h) was not affected by serum lipoprotein levels. Conclusion: In cell culture, BOPP is taken up by human glioma cells via the LDL pathway and is compartmentalized into cellular lysosomes. Knowledge of this mechanism of BOPP uptake and retention will be important in attempts to modify toxicity and efficacy of this drug

  16. The Burkholderia pseudomallei Proteins BapA and BapC Are Secreted TTSS3 Effectors and BapB Levels Modulate Expression of BopE.

    Directory of Open Access Journals (Sweden)

    Puthayalai Treerat

    Full Text Available Many Gram-negative pathogens use a type III secretion system (TTSS for the injection of bacterial effector proteins into host cells. The injected effector proteins play direct roles in modulation of host cell pathways for bacterial benefit. Burkholderia pseudomallei, the causative agent of melioidosis, expresses three different TTSSs. One of these systems, the TTSS3, is essential for escape from host endosomes and therefore intracellular survival and replication. Here we have characterized three putative TTSS3 proteins; namely BapA, BapB and BapC. By employing a tetracysteine (TC-FlAsH™ labelling technique to monitor the secretion of TC-tagged fusion proteins, BapA and BapC were shown to be secreted during in vitro growth in a TTSS3-dependant manner, suggesting a role as TTSS3 effectors. Furthermore, we constructed B. pseudomallei bapA, bapB and bapC mutants and used the well-characterized TTSS3 effector BopE as a marker of secretion to show that BapA, BapB and BapC are not essential for the secretion process. However, BopE transcription and secretion were significantly increased in the bapB mutant, suggesting that BapB levels modulate BopE expression. In a BALB/c mouse model of acute melioidosis, the bapA, bapB and bapC mutants showed a minor reduction of in vivo fitness. Thus, this study defines BapA and BapC as novel TTSS3 effectors, BapB as a regulator of BopE production, and all three as necessary for full B. pseudomallei in vivo fitness.

  17. Maternal consumption of high-fat diet and grape juice modulates global histone H4 acetylation levels in offspring hippocampus: A preliminary study.

    Science.gov (United States)

    Gonçalves, Luciana Kneib; da Silva, Ivy Reichert Vital; Cechinel, Laura Reck; Frusciante, Marina Rocha; de Mello, Alexandre Silva; Elsner, Viviane Rostirola; Funchal, Claudia; Dani, Caroline

    2017-11-20

    This study aimed to investigate the impact of maternal consumption of a hyperlipid diet and grape juice on global histone H4 acetylation levels in the offsprinǵs hippocampus at different stages of development. During pregnancy and lactation of offspring, dams were divided into 4 groups: control diet (CD), high-fat diet (HFD), control diet and purple grape juice (PGJCD) and purple grape juice and high-fat diet (PGJHFD). Male Wistar rats were euthanized at 21days of age (PN21, adolescents) and at 50days of age (PN50, adults). The maternal consumption of grape juice increased global histone H4 acetylation levels in hippocampus of adolescents pups (PN21), an indicative of enhanced transcriptional activity and increased gene expression. On the other hand, the maternal high-fat diet diminished significantly this epigenetic marker in the adult phase (PN50), suggesting gene silencing. These preliminary findings demonstrated that the maternal choices are able to induce changes on histone H4 acetylation status in hippocampus of the offspring, which may modulate the expression of specific genes. Interestingly, this response occurs in an age and stimuli-dependent manner and strongly reinforce the importance of maternal choices during gestation. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Dlk1/FA1 is a novel endocrine regulator of bone and fat mass and its serum level is modulated by growth hormone

    DEFF Research Database (Denmark)

    Abdallah, Basem; Ding, Ming; Jensen, Charlotte H

    2007-01-01

    Fat and bone metabolism are two linked processes regulated by several hormonal factors. Fetal antigen 1 (FA1) is the soluble form of dlk1 (delta-like 1), which is a member of the Notch-Delta family. We previously identified FA1 as a negative regulator of bone marrow mesenchymal stem cell...... differentiation. Here, we studied the effects of circulating FA1 on fat and bone mass in vivo by generating mice expressing high serum levels of FA1 (FA1 mice) using the hydrodynamic-based gene transfer procedure. We found that increased serum FA1 levels led to a significant reduction in total body weight, fat...... mass, and bone mass in a dose-dependent manner. Reduced bone mass in FA1 mice was associated with the inhibition of mineral apposition rate and bone formation rates by 58 and 72%, respectively. Because FA1 is colocalized with GH in the pituitary gland, we explored the possible modulation of serum FA1...

  19. Connexin31.1 deficiency in the mouse impairs object memory and modulates open-field exploration, acetylcholine esterase levels in the striatum, and cAMP response element-binding protein levels in the striatum and piriform cortex.

    Science.gov (United States)

    Dere, E; Zheng-Fischhöfer, Q; Viggiano, D; Gironi Carnevale, U A; Ruocco, L A; Zlomuzica, A; Schnichels, M; Willecke, K; Huston, J P; Sadile, A G

    2008-05-02

    Neuronal gap junctions in the brain, providing intercellular electrotonic signal transfer, have been implicated in physiological and behavioral correlates of learning and memory. In connexin31.1 (Cx31.1) knockout (KO) mice the coding region of the Cx31.1 gene was replaced by a LacZ reporter gene. We investigated the impact of Cx31.1 deficiency on open-field exploration, the behavioral response to an odor, non-selective attention, learning and memory performance, and the levels of memory-related proteins in the hippocampus, striatum and the piriform cortex. In terms of behavior, the deletion of the Cx31.1 coding DNA in the mouse led to increased exploratory behaviors in a novel environment, and impaired one-trial object recognition at all delays tested. Despite strong Cx31.1 expression in the peripheral and central olfactory system, Cx31.1 KO mice exhibited normal behavioral responses to an odor. We found increased levels of acetylcholine esterase (AChE) and cAMP response element-binding protein (CREB) in the striatum of Cx31.1 KO mice. In the piriform cortex the Cx31.1 KO mice had an increased heterogeneity of CREB expression among neurons. In conclusion, gap-junctions featuring the Cx31.1 protein might be involved in open-field exploration as well as object memory and modulate levels of AChE and CREB in the striatum and piriform cortex.

  20. Security Injections 2.0: Increasing Engagement and Faculty Adoption Using Enhanced Secure Coding Modules for Lower-Level Programming Courses

    OpenAIRE

    Raina , Sagar; Taylor , Blair; Kaza , Siddharth

    2015-01-01

    Part 2: Software Security Education; International audience; Learning interventions based on modules are common in computer science education. Traditional learning modules that present a large amount of content in a linear format can lead to students skimming and skipping content resulting in lower student engagement and effectiveness. In this paper, we present theoretical support for increasing engagement and effectiveness of learning modules, describe a system that implements these principl...

  1. A two-level voltage source inverter with differentially sinusoidal pulse width modulation used in the interconnection system of a wind turbine generator

    Directory of Open Access Journals (Sweden)

    Alexandros C. Charalampidis

    2014-10-01

    Full Text Available This study analyses an interconnection system based on differentially sinusoidal pulse width modulation, used for the interconnection to the grid of a variable speed wind turbine. The modulation technique used provides specific advantages in comparison with the commonly used sinusoidal pulse width modulation (SPWM technique, such as lower DC bus voltage requirements, smaller switching losses for the same switching frequency as well as less higher harmonic content in the voltage waveforms produced. The respective control system is also described in detail. Thus this study provides a guide enabling the design of any interconnection system based on this modulation technique.

  2. Etazolate rescues behavioral deficits in chronic unpredictable mild stress model: modulation of hypothalamic-pituitary-adrenal axis activity and brain-derived neurotrophic factor level.

    Science.gov (United States)

    Jindal, Ankur; Mahesh, Radhakrishnan; Bhatt, Shvetank

    2013-11-01

    effect of etazolate and fluoxetine on CORT and BDNF levels in normal control mice. In conclusion, the results of the present study suggested compelling evidences that etazolate has more marked effect on depression-like behavior in mice, which is atleast in part may be related to their modulating effects on the HPA axis and BDNF level. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Antioxidant enzyme activity and malondialdehyde levels can be modulated by Piper betle, tocotrienol rich fraction and Chlorella vulgaris in aging C57BL/6 mice.

    Science.gov (United States)

    Aliahmat, Nor Syahida; Noor, Mohd Razman Mohd; Yusof, Wan Junizam Wan; Makpol, Suzana; Ngah, Wan Zurinah Wan; Yusof, Yasmin Anum Mohd

    2012-12-01

    The aim of this study was to determine the erythrocyte antioxidant enzyme activity and the superoxide dismutase, catalase, glutathione peroxidase, and plasma malondialdehyde levels in aging mice and to evaluate how these measures are modulated by potential antioxidants, including the tocotrienol-rich fraction, Piper betle, and Chlorella vulgaris. One hundred and twenty male C57BL/6 inbred mice were divided into three age groups: young (6 months old), middle-aged (12 months old), and old (18 months old). Each age group consisted of two control groups (distilled water and olive oil) and three treatment groups: Piper betle (50 mg/kg body weight), tocotrienol-rich fraction (30 mg/kg), and Chlorella vulgaris (50 mg/kg). The duration of treatment for all three age groups was two months. Blood was withdrawn from the orbital sinus to determine the antioxidant enzyme activity and the malondialdehyde level. Piper betle increased the activities of catalase, glutathione peroxidase, and superoxide dismutase in the young, middle, and old age groups, respectively, when compared to control. The tocotrienol-rich fraction decreased the superoxide dismutase activity in the middle and the old age groups but had no effect on catalase or glutathione peroxidase activity for all age groups. Chlorella vulgaris had no effect on superoxide dismutase activity for all age groups but increased glutathione peroxidase and decreased catalase activity in the middle and the young age groups, respectively. Chlorella vulgaris reduced lipid peroxidation (malondialdehyde levels) in all age groups, but no significant changes were observed with the tocotrienol-rich fraction and the Piper betle treatments. We found equivocal age-related changes in erythrocyte antioxidant enzyme activity when mice were treated with Piper betle, the tocotrienol-rich fraction, and Chlorella vulgaris. However, Piper betle treatment showed increased antioxidant enzymes activity during aging.

  4. Antioxidant enzyme activity and malondialdehyde levels can be modulated by Piper betle, tocotrienol rich fraction and Chlorella vulgaris in aging C57BL/6 mice

    Directory of Open Access Journals (Sweden)

    Nor Syahida Aliahmat

    2012-12-01

    Full Text Available OBJECTIVE: The aim of this study was to determine the erythrocyte antioxidant enzyme activity and the superoxide dismutase, catalase, glutathione peroxidase, and plasma malondialdehyde levels in aging mice and to evaluate how these measures are modulated by potential antioxidants, including the tocotrienol-rich fraction, Piper betle, and Chlorella vulgaris. METHOD: One hundred and twenty male C57BL/6 inbred mice were divided into three age groups: young (6 months old, middle-aged (12 months old, and old (18 months old. Each age group consisted of two control groups (distilled water and olive oil and three treatment groups: Piper betle (50 mg/kg body weight, tocotrienol-rich fraction (30 mg/kg, and Chlorella vulgaris (50 mg/kg. The duration of treatment for all three age groups was two months. Blood was withdrawn from the orbital sinus to determine the antioxidant enzyme activity and the malondialdehyde level. RESULTS: Piper betle increased the activities of catalase, glutathione peroxidase, and superoxide dismutase in the young, middle, and old age groups, respectively, when compared to control. The tocotrienol-rich fraction decreased the superoxide dismutase activity in the middle and the old age groups but had no effect on catalase or glutathione peroxidase activity for all age groups. Chlorella vulgaris had no effect on superoxide dismutase activity for all age groups but increased glutathione peroxidase and decreased catalase activity in the middle and the young age groups, respectively. Chlorella vulgaris reduced lipid peroxidation (malondialdehyde levels in all age groups, but no significant changes were observed with the tocotrienol-rich fraction and the Piper betle treatments. CONCLUSION: We found equivocal age-related changes in erythrocyte antioxidant enzyme activity when mice were treated with Piper betle, the tocotrienol-rich fraction, and Chlorella vulgaris. However, Piper betle treatment showed increased antioxidant enzymes

  5. Modulation of phosducin-like protein 3 (PhLP3 levels promotes cytoskeletal remodelling in a MAPK and RhoA-dependent manner.

    Directory of Open Access Journals (Sweden)

    Nandini V L Hayes

    Full Text Available Phosducin-like protein 3 (PhLP3 forms a ternary complex with the ATP-dependent molecular chaperone CCT and its folding client tubulin. In vitro studies suggest PhLP3 plays an inhibitory role in β-tubulin folding while conversely in vivo genetic studies suggest PhLP3 is required for the correct folding of β-tubulin. We have a particular interest in the cytoskeleton, its chaperones and their role in determining cellular phenotypes associated with high level recombinant protein expression from mammalian cell expression systems.As studies into PhLP3 function have been largely carried out in non mammalian systems, we examined the effect of human PhLP3 over-expression and siRNA silencing using a single murine siRNA on both tubulin and actin systems in mammalian Chinese hamster ovary (CHO cell lines. We show that over-expression of PhLP3 promotes an imbalance of α and β tubulin subunits, microtubule disassembly and cell death. In contrast, β-actin levels are not obviously perturbed. On-the-other-hand, RNA silencing of PhLP3 increases RhoA-dependent actin filament formation and focal adhesion formation and promotes a dramatic elongated fibroblast-like change in morphology. This was accompanied by an increase in phosphorylated MAPK which has been associated with promoting focal adhesion assembly and maturation. Transient overexpression of PhLP3 in knockdown experiments rescues cells from the morphological change observed during PhLP3 silencing but mitosis is perturbed, probably reflecting a tipping back of the balance of PhLP3 levels towards the overexpression state.Our results support the hypothesis that PhLP3 is important for the maintenance of β-tubulin levels in mammalian cells but also that its modulation can promote actin-based cytoskeletal remodelling by a mechanism linked with MAPK phosphorylation and RhoA-dependent changes. PhLP3 levels in mammalian cells are thus finely poised and represents a novel target for engineering industrially

  6. Comparing success levels of different neural network structures in extracting discriminative information from the response patterns of a temperature-modulated resistive gas sensor

    Science.gov (United States)

    Hosseini-Golgoo, S. M.; Bozorgi, H.; Saberkari, A.

    2015-06-01

    Performances of three neural networks, consisting of a multi-layer perceptron, a radial basis function, and a neuro-fuzzy network with local linear model tree training algorithm, in modeling and extracting discriminative features from the response patterns of a temperature-modulated resistive gas sensor are quantitatively compared. For response pattern recording, a voltage staircase containing five steps each with a 20 s plateau is applied to the micro-heater of the sensor, when 12 different target gases, each at 11 concentration levels, are present. In each test, the hidden layer neuron weights are taken as the discriminatory feature vector of the target gas. These vectors are then mapped to a 3D feature space using linear discriminant analysis. The discriminative information content of the feature vectors are determined by the calculation of the Fisher’s discriminant ratio, affording quantitative comparison among the success rates achieved by the different neural network structures. The results demonstrate a superior discrimination ratio for features extracted from local linear neuro-fuzzy and radial-basis-function networks with recognition rates of 96.27% and 90.74%, respectively.

  7. Comparing success levels of different neural network structures in extracting discriminative information from the response patterns of a temperature-modulated resistive gas sensor

    International Nuclear Information System (INIS)

    Hosseini-Golgoo, S M; Bozorgi, H; Saberkari, A

    2015-01-01

    Performances of three neural networks, consisting of a multi-layer perceptron, a radial basis function, and a neuro-fuzzy network with local linear model tree training algorithm, in modeling and extracting discriminative features from the response patterns of a temperature-modulated resistive gas sensor are quantitatively compared. For response pattern recording, a voltage staircase containing five steps each with a 20 s plateau is applied to the micro-heater of the sensor, when 12 different target gases, each at 11 concentration levels, are present. In each test, the hidden layer neuron weights are taken as the discriminatory feature vector of the target gas. These vectors are then mapped to a 3D feature space using linear discriminant analysis. The discriminative information content of the feature vectors are determined by the calculation of the Fisher’s discriminant ratio, affording quantitative comparison among the success rates achieved by the different neural network structures. The results demonstrate a superior discrimination ratio for features extracted from local linear neuro-fuzzy and radial-basis-function networks with recognition rates of 96.27% and 90.74%, respectively. (paper)

  8. The effects of social isolation on steroid hormone levels are modulated by previous social status and context in a cichlid fish.

    Science.gov (United States)

    Galhardo, L; Oliveira, R F

    2014-01-01

    Social isolation is a major stressor which impacts the physiology, behaviour and health of individuals in gregarious species. However, depending on conditional and contextual factors, such as social status and group composition, social isolation may be perceived differently by different individuals or even by the same individuals at different times. Here we tested the effects of social status (territorial vs. non-territorial) and previous group composition (i.e. type of social group: mixed sex group with two territorial males, TT vs. mixed sex group with one territorial and one non-territorial male, TnT) on the hormonal response (androgens and cortisol) to social isolation in a cichlid fish (Oreochromis mossambicus). The different steroid hormones measured responded differentially to social isolation, and their response was modulated by social factors. Social isolation elicited a decrease of 11-keto formation only in territorial males, whereas non-territorial males present a non-significant trend for increasing KT levels. Testosterone did not respond to social isolation. Cortisol only increased in isolated individuals from TnT groups irrespective of social status (i.e. both in territorials and non-territorials). These results suggest that it is the perception of social isolation and not the objective structure of the situation that triggers the hormonal response to isolation. © 2013.

  9. 2.3-MW Medium-Voltage, Three-Level Wind Energy Inverter Applying a Unique Bus Structure and 4.5-kV Si/SiC Hybrid Isolated Power Modules: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Erdman, W.; Keller, J.; Grider, D.; VanBrunt, E.

    2014-11-01

    A high-efficiency, 2.3-MW, medium-voltage, three-level inverter utilizing 4.5-kV Si/SiC (silicon carbide) hybrid modules for wind energy applications is discussed. The inverter addresses recent trends in siting the inverter within the base of multimegawatt turbine towers. A simplified split, three-layer laminated bus structure that maintains low parasitic inductances is introduced along with a low-voltage, high-current test method for determining these inductances. Feed-thru bushings, edge fill methods, and other design features of the laminated bus structure provide voltage isolation that is consistent with the 10.4-kV module isolation levels. Inverter efficiency improvement is a result of the (essential) elimination of the reverse recovery charge present in 4.5-kV Si PIN diodes, which can produce a significant reduction in diode turn-off losses as well as insulated-gate bipolar transistor (IGBT) turn-on losses. The hybrid modules are supplied in industry-standard 140 mm x 130 mm and 190 mm x 130 mm packages to demonstrate direct module substitution into existing inverter designs. A focus on laminated bus/capacitor-bank/module subassembly level switching performance is presented.

  10. Aboveground Whitefly Infestation Modulates Transcriptional Levels of Anthocyanin Biosynthesis and Jasmonic Acid Signaling-Related Genes and Augments the Cope with Drought Stress of Maize.

    Directory of Open Access Journals (Sweden)

    Yong-Soon Park

    Full Text Available Up to now, the potential underlying molecular mechanisms by which maize (Zea mays L. plants elicit defense responses by infestation with a phloem feeding insect whitefly [Bemisia tabaci (Genn.] have been barely elucidated against (abiotic stresses. To fill this gap of current knowledge maize plants were infested with whitefly and these plants were subsequently assessed the levels of water loss. To understand the mode of action, plant hormone contents and the stress-related mRNA expression were evaluated. Whitefly-infested maize plants did not display any significant phenotypic differences in above-ground tissues (infested site compared with controls. By contrast, root (systemic tissue biomass was increased by 2-fold by whitefly infestation. The levels of endogenous indole-3-acetic acid (IAA, jasmonic acid (JA, and hydrogen peroxide (H2O2 were significantly higher in whitefly-infested plants. The biosynthetic or signaling-related genes for JA and anthocyanins were highly up-regulated. Additionally, we found that healthier plants were obtained in whitefly-infested plants under drought conditions. The weight of whitefly-infested plants was approximately 20% higher than that of control plants at 14 d of drought treatment. The drought tolerance-related genes, ZmbZIP72, ZmSNAC1, and ZmABA1, were highly expressed in the whitefly-infected plants. Collectively, our results suggest that IAA/JA-derived maize physiological changes and correlation of H2O2 production and water loss are modulated by above-ground whitefly infestation in maize plants.

  11. The selective estrogen receptor modulators (SERMs) raloxifene and tamoxifen improve ANP levels and decrease nuclear translocation of NF-kB in estrogen-deficient rats.

    Science.gov (United States)

    Lamas, Aline Z; Nascimento, Andrews M; Medeiros, Ana Raquel S; Caliman, Izabela F; Dalpiaz, Polyana L M; Firmes, Luciana B; Sousa, Glauciene J; Oliveira, Phablo Wendell C; Andrade, Tadeu U; Reis, Adelina M; Gouvea, Sônia A; Bissoli, Nazaré S

    2017-08-01

    The selective estrogen receptor modulators (SERMs) raloxifene and tamoxifen are used for the treatment of osteoporosis and cancer, respectively, in women. The impairment of both the Atrial Natriuretic Peptide (ANP) cell signaling system and the translocation of nuclear factor-kappa B (NF-kB) to the cell nucleus are associated with detrimental cardiovascular effects and inflammation. The effects of SERMs on these parameters in the cardiac tissue of estrogen-deficient rats has not been reported. We investigated the effects of raloxifene and tamoxifen on ANP signaling, p65 NF-kB nuclear translocation, cardiac histology and contractility. Female rats were divided into five groups: control (SHAM), ovariectomized (OVX), OVX-treated 17-β-estradiol (E), OVX-treated raloxifene (RLX) and OVX-treated tamoxifen (TAM). The treatments started 21days after ovariectomy and continued for 14days. Ovariectomy reduced ANP mRNA in the left atrium (LA), decreased the content of ANP protein in the LA and in plasma, and increased the level of p65 NF-kB nuclear translocation in the left ventricle. Both 17-β-estradiol and SERMs were able to reverse these alterations, which were induced by the estrogen deficient state. The hemodynamic and cardiac structural parameters analyzed in the present work were not modified by the interventions. Our study demonstrates, for the first time, the additional benefits of raloxifene and tamoxifen in an estrogen-deficient state. These include the normalization of plasmatic and cardiac ANP levels and cardiac p65 NF-kB translocation. Therefore, these treatments promote cardiovascular protection and may contribute to the prevention of cardiac dysfunction observed long-term in postmenopausal women. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

  12. Tolerance of citrus plants to the combination of high temperatures and drought is associated to the increase in transpiration modulated by a reduction in abscisic acid levels.

    Science.gov (United States)

    Zandalinas, Sara I; Rivero, Rosa M; Martínez, Vicente; Gómez-Cadenas, Aurelio; Arbona, Vicent

    2016-04-27

    In natural environments, several adverse environmental conditions occur simultaneously constituting a unique stress factor. In this work, physiological parameters and the hormonal regulation of Carrizo citrange and Cleopatra mandarin, two citrus genotypes, in response to the combined action of high temperatures and water deprivation were studied. The objective was to characterize particular responses to the stress combination. Experiments indicated that Carrizo citrange is more tolerant to the stress combination than Cleopatra mandarin. Furthermore, an experimental design spanning 24 h stress duration, heat stress applied alone induced higher stomatal conductance and transpiration in both genotypes whereas combined water deprivation partially counteracted this response. Comparing both genotypes, Carrizo citrange showed higher phostosystem-II efficiency and lower oxidative damage than Cleopatra mandarin. Hormonal profiling in leaves revealed that salicylic acid (SA) accumulated in response to individual stresses but to a higher extent in samples subjected to the combination of heat and drought (showing an additive response). SA accumulation correlated with the up-regulation of pathogenesis-related gene 2 (CsPR2), as a downstream response. On the contrary, abscisic acid (ABA) accumulation was higher in water-stressed plants followed by that observed in plants under stress combination. ABA signaling in these plants was confirmed by the expression of responsive to ABA-related gene 18 (CsRAB18). Modulation of ABA levels was likely carried out by the induction of 9-neoxanthin cis-epoxicarotenoid dioxygenase (CsNCED) and ABA 8'-hydroxylase (CsCYP707A) while conversion to ABA-glycosyl ester (ABAGE) was a less prominent process despite the strong induction of ABA O-glycosyl transferase (CsAOG). Cleopatra mandarin is more susceptible to the combination of high temperatures and water deprivation than Carrizo citrange. This is likely a result of a higher transpiration rate in

  13. Horticultural therapy: a pilot study on modulating cortisol levels and indices of substance craving, posttraumatic stress disorder, depression, and quality of life in veterans.

    Science.gov (United States)

    Detweiler, Mark B; Self, Jennifer A; Lane, Sandra; Spencer, Luise; Lutgens, Brian; Kim, Dong-Yun; Halling, Mary H; Rudder, Tammie C; Lehmann, Lauren P

    2015-01-01

    programmed activities. The trends suggest that HT may modulate stress in veterans, as evidenced by decreased cortisol levels and depressive symptoms, and may improve quality of life more than the programs in which the OT group participated. Further investigation with larger samples, including a nontreatment control group, is needed to determine whether the observed trends are treatment effects or due to abstinence.

  14. Valence States Modulation Strategy for Picomole Level Assay of Hg2+ in Drinking and Environmental Water by Directional Self-Assembly of Gold Nanorods.

    Science.gov (United States)

    Chen, Lu; Lu, Linlin; Wang, Sufan; Xia, Yunsheng

    2017-06-23

    In this study, we present a valence states modulation strategy for picomole level assay of Hg 2+ using directional self-assembly of gold nanorods (AuNRs) as signal readout. Hg 2+ ions are first controllably reduced to Hg + ions by appropriate ascorbic acid, and the reduced Hg + ions react with the tips of the preadded AuNRs and form gold amalgam. Such Hg + decorated AuNRs then end-to-end self-assemble into one-dimensional architectures by the bridging effects of lysine based on the high affinity of NH 2 -Hg + interactions. Correspondingly, the AuNRs' longitudinal surface plasmon resonance is gradually reduced and a new broad band appears at 900-1100 nm region simultaneously. The resulting distinctly ratiometric signal output is not only favorable for Hg 2+ ions detection but competent for their quantification. Under optimal conditions, the linear range is 22.8 pM to 11.4 nM, and the detection limit is as low as 8.7 pM. Various transition/heavy metal ions, such as Pb 2+ , Ti 2+ , Co 2+ , Fe 3+ , Mn 2+ , Ba 2+ , Fe 2+ , Ni 2+ , Al 3+ , Cu 2+ , Ag + , and Au 3+ , do not interfere with the assay. Because of ultrahigh sensitivity and excellent selectivity, the proposed system can be employed for assaying ultratrace of Hg 2+ containing in drinking and commonly environmental water samples, which is difficult to be achieved by conventional colorimetric systems. These results indicate that the present platform possesses specific advantages and potential applications in the assay of ultratrace amounts of Hg 2+ ions.

  15. Loss of Pnn expression attenuates expression levels of SR family splicing factors and modulates alternative pre-mRNA splicing in vivo

    International Nuclear Information System (INIS)

    Chiu Yali; Ouyang Pin

    2006-01-01

    SR and SR-related proteins have been implicated as trans-acting factors that play an important role in splice selection and are involved at specific stages of spliceosome formation. A well-established property of SR protein splicing factors is their ability to influence selection of alternative splice sites in a concentration-dependent manner. Identification of molecules that regulate SR family protein expression is therefore of vital importance in RNA biology. Here we report that depletion of Pnn expression, a SR-related protein with functions involved in pre-mRNA splicing and mRNA export, induces reduced expression of a subset of cellular proteins, especially that of SR family proteins, including SC35, SRm300, SRp55, and SRp40, but not that of other nuclear proteins, such as p53, Mdm2, and ki67. Knocking down Pnn expression was achieved in vitro by siRNA transfection. Expression levels of SR and SR-related proteins in Pnn-depleted cells as compared to those in control cells were evaluated by immunofluorescent staining and Western blot with specific antibodies. In addition, we also demonstrate that loss of Pnn expression could modulate splice site selection of model reporter gene in vivo. Our finding is significant in terms of regulation of SR protein cellular concentration because it reveals that Pnn may play a general role in the control of the cellular amount of family SR proteins through down-regulation of its own expression, thereby providing us with a better understanding of the cellular mechanism by which Pnn fulfills its biological function

  16. Positive and negative early life experiences differentially modulate long term survival and amyloid protein levels in a mouse model of Alzheimer’s disease

    NARCIS (Netherlands)

    Lesuis, S.L.; Maurin, H.; Borghgraef, P.; Lucassen, P.J.; Van Leuven, F.; Krugers, H.J.

    2016-01-01

    Stress has been implicated as a risk factor for the severity and progression of sporadic Alzheimer's disease (AD). Early life experiences determine stress responsivity in later life, and modulate age-dependent cognitive decline. Therefore, we examined whether early life experiences influence AD

  17. Periodically modulated dark states

    Science.gov (United States)

    Han, Yingying; Zhang, Jun; Zhang, Wenxian

    2018-04-01

    Phenomena of electromagnetically induced transparency (PEIT) may be interpreted by the Autler-Townes Splitting (ATS), where the coupled states are split by the coupling laser field, or by the quantum destructive interference (QDI), where the atomic phases caused by the coupling laser and the probe laser field cancel. We propose modulated experiments to explore the PEIT in an alternative way by periodically modulating the coupling and the probe fields in a Λ-type three-level system initially in a dark state. Our analytical and numerical results rule out the ATS interpretation and show that the QDI interpretation is more appropriate for the modulated experiments. Interestingly, dark state persists in the double-modulation situation where control and probe fields never occur simultaneously, which is significant difference from the traditional dark state condition. The proposed experiments are readily implemented in atomic gases, artificial atoms in superconducting quantum devices, or three-level meta-atoms in meta-materials.

  18. Medical Terminology: Suffixes. Health Occupations Education Module.

    Science.gov (United States)

    Temple Univ., Philadelphia, PA. Div. of Vocational Education.

    This module on medical terminology (suffixes) is one of 17 modules designed for individualized instruction in health occupations education programs at both the secondary and postsecondary levels. This module consists of an introduction to the module topic, a list of resources needed, and three learning experiences. The first two learning…

  19. Low-cost solar module manufacturing

    International Nuclear Information System (INIS)

    Little, Roger G.; Nowlan, Michael J.; Matthei, Keith W.; Darkazalli, Ghazi

    1997-01-01

    As the market for terrestrial photovoltaic modules expands beyond the 80 MW per year level, module manufacturers are adopting a number of cost-reduction strategies, including the use of higher throughput equipment, increased process automation, and the fabrication of larger area cells and modules. This paper reviews recent activities at Spire Corporation in the development of advanced module manufacturing and testing equipment

  20. Health Occupations Module. The Integumentary System.

    Science.gov (United States)

    Temple Univ., Philadelphia, PA. Div. of Vocational Education.

    This module on the integumentary system is one of eight modules designed for individualized instruction in health occupations education programs at both the secondary and postsecondary levels. This module contains an introduction to the module topic, objectives (e.g., list and describe the types of glands formed in the skin, and explain the…

  1. Activation of the human complement system by cholesterol-rich and pegylated liposomes - Modulation of cholesterol-rich liposome-mediated complement activation by elevated serum LDL and HDL levels

    DEFF Research Database (Denmark)

    Moghimi, S.M.; Hamad, I.; Bunger, R.

    2006-01-01

    level of S-protein-bound form of the terminal complex (SC5b-9). However, liposome-induced rise of SC5b-9 was significantly suppressed when serum HDL cholesterol levels increased by 30%. Increase of serum LDL to levels similar to that observed in heterozygous familial hypercholesterolemia also suppressed......Intravenously infused liposomes may induce cardiopulmonary distress in some human subjects, which is a manifestation of "complement activation-related pseudoallergy." We have now examined liposome-mediated complement activation in human sera with elevated lipoprotein (LDL and HDL) levels, since...... abnormal or racial differences in serum lipid profiles seem to modulate the extent of complement activation and associated adverse responses. In accordance with our earlier observations, cholesterol-rich (45 mol% cholesterol) liposomes activated human complement, as reflected by a significant rise in serum...

  2. Arabidopsis Glutamate Receptor Homolog3.5 Modulates Cytosolic Ca2+ Level to Counteract Effect of Abscisic Acid in Seed Germination1[OPEN

    Science.gov (United States)

    Kong, Dongdong; Ju, Chuanli; Parihar, Aisha; Kim, So; Cho, Daeshik; Kwak, June M.

    2015-01-01

    Seed germination is a critical step in a plant’s life cycle that allows successful propagation and is therefore strictly controlled by endogenous and environmental signals. However, the molecular mechanisms underlying germination control remain elusive. Here, we report that the Arabidopsis (Arabidopsis thaliana) glutamate receptor homolog3.5 (AtGLR3.5) is predominantly expressed in germinating seeds and increases cytosolic Ca2+ concentration that counteracts the effect of abscisic acid (ABA) to promote germination. Repression of AtGLR3.5 impairs cytosolic Ca2+ concentration elevation, significantly delays germination, and enhances ABA sensitivity in seeds, whereas overexpression of AtGLR3.5 results in earlier germination and reduced seed sensitivity to ABA. Furthermore, we show that Ca2+ suppresses the expression of ABSCISIC ACID INSENSITIVE4 (ABI4), a key transcription factor involved in ABA response in seeds, and that ABI4 plays a fundamental role in modulation of Ca2+-dependent germination. Taken together, our results provide molecular genetic evidence that AtGLR3.5-mediated Ca2+ influx stimulates seed germination by antagonizing the inhibitory effects of ABA through suppression of ABI4. These findings establish, to our knowledge, a new and pivotal role of the plant glutamate receptor homolog and Ca2+ signaling in germination control and uncover the orchestrated modulation of the AtGLR3.5-mediated Ca2+ signal and ABA signaling via ABI4 to fine-tune the crucial developmental process, germination, in Arabidopsis. PMID:25681329

  3. Polysaccharides from the fungus Scleroderma nitidum with anti-inflammatory potential modulate cytokine levels and the expression of Nuclear Factor kB

    Directory of Open Access Journals (Sweden)

    Marília S. Nascimento

    2012-02-01

    Full Text Available Several pharmacological properties are attributed to polysaccharides and glucans derived from fungi such as tumor, anti-inflammatory, and immunomodulatory activity. In this work, the anti-inflammatory potential of polysaccharides from the fungus Scleroderma nitidum and their possible action mechanism were studied. The effect of these polymers on the inflammatory process was tested using the carrageenan and histamine-induced paw edema model and the sodium thioglycolate and zymosan-induced model. The polysaccharides from S. nitidum were effective in reducing edema (73% at 50 mg/kg and cell infiltrate (37% at 10 mg/kg in both inflammation models tested. Nitric oxide, a mediator in the inflammatory process, showed a reduction of around 26% at 10 mg/kg of body weight. Analysis of pro-and anti-inflammatory cytokines showed that in the groups treated with polysaccharides from S. nitidum there was an increase in cytokines such as IL-1ra, IL-10, and MIP-1β concomitant with the decrease in INF-γ (75% and IL-2 (22%. We observed the influence of polysaccharides on the modulation of the expression of nuclear factor κB. This compound reduced the expression of NF-κB by up to 64%. The results obtained suggest that NF-κB modulation an mechanisms that explain the anti-inflammatory effect of polysaccharides from the fungus S. nitidum.

  4. A photovoltaic module

    DEFF Research Database (Denmark)

    2013-01-01

    The present invention relates to a photovoltaic module comprising a carrier substrate, said carrier substrate carrying a purely printed structure comprising printed positive and negative module terminals, a plurality of printed photovoltaic cell units each comprising one or more printed...... photovoltaic cells, wherein the plurality of printed photovoltaic cell units are electrically connected in series between the positive and the negative module terminals such that any two neighbouring photovoltaic cell units are electrically connected by a printed interconnecting electrical conductor....... The carrier substrate comprises a foil and the total thickness of the photovoltaic module is below 500 [mu]m. Moreover, the nominal voltage level between the positive and the negative terminals is at least 5 kV DC....

  5. Human Milk and Donkey Milk, Compared to Cow Milk, Reduce Inflammatory Mediators and Modulate Glucose and Lipid Metabolism, Acting on Mitochondrial Function and Oleylethanolamide Levels in Rat Skeletal Muscle.

    Science.gov (United States)

    Trinchese, Giovanna; Cavaliere, Gina; De Filippo, Chiara; Aceto, Serena; Prisco, Marina; Chun, Jong Tai; Penna, Eduardo; Negri, Rossella; Muredda, Laura; Demurtas, Andrea; Banni, Sebastiano; Berni-Canani, Roberto; Mattace Raso, Giuseppina; Calignano, Antonio; Meli, Rosaria; Greco, Luigi; Crispino, Marianna; Mollica, Maria P

    2018-01-01

    Scope: Milk from various species differs in nutrient composition. In particular, human milk (HM) and donkey milk (DM) are characterized by a relative high level of triacylglycerol enriched in palmitic acid in sn-2 position. These dietary fats seem to exert beneficial nutritional properties through N-acylethanolamine tissue modulation. The aim of this study is to compare the effects of cow milk (CM), DM, and HM on inflammation and glucose and lipid metabolism, focusing on mitochondrial function, efficiency, and dynamics in skeletal muscle, which is the major determinant of resting metabolic rate. Moreover, we also evaluated the levels of endocannabinoids and N-acylethanolamines in liver and skeletal muscle, since tissue fatty acid profiles can be modulated by nutrient intervention. Procedures: To this aim, rats were fed with CM, DM, or HM for 4 weeks. Then, glucose tolerance and insulin resistance were analyzed. Pro-inflammatory and anti-inflammatory cytokines were evaluated in serum and skeletal muscle. Skeletal muscle was also processed to estimate mitochondrial function, efficiency, and dynamics, oxidative stress, and antioxidant/detoxifying enzyme activities. Fatty acid profiles, endocannabinoids, and N-acylethanolamine congeners were determined in liver and skeletal muscle tissue. Results: We demonstrated that DM or HM administration reducing inflammation status, improves glucose disposal and insulin resistance and reduces lipid accumulation in skeletal muscle. Moreover, HM or DM administration increases redox status, and mitochondrial uncoupling, affecting mitochondrial dynamics in the skeletal muscle. Interestingly, HM and DM supplementation increase liver and muscle levels of the N-oleoylethanolamine (OEA), a key regulator of lipid metabolism and inflammation. Conclusions: HM and DM have a healthy nutritional effect, acting on inflammatory factors and glucose and lipid metabolism. This beneficial effect is associated to a modulation of mitochondrial function

  6. Human Milk and Donkey Milk, Compared to Cow Milk, Reduce Inflammatory Mediators and Modulate Glucose and Lipid Metabolism, Acting on Mitochondrial Function and Oleylethanolamide Levels in Rat Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Giovanna Trinchese

    2018-01-01

    Full Text Available Scope: Milk from various species differs in nutrient composition. In particular, human milk (HM and donkey milk (DM are characterized by a relative high level of triacylglycerol enriched in palmitic acid in sn-2 position. These dietary fats seem to exert beneficial nutritional properties through N-acylethanolamine tissue modulation. The aim of this study is to compare the effects of cow milk (CM, DM, and HM on inflammation and glucose and lipid metabolism, focusing on mitochondrial function, efficiency, and dynamics in skeletal muscle, which is the major determinant of resting metabolic rate. Moreover, we also evaluated the levels of endocannabinoids and N-acylethanolamines in liver and skeletal muscle, since tissue fatty acid profiles can be modulated by nutrient intervention.Procedures: To this aim, rats were fed with CM, DM, or HM for 4 weeks. Then, glucose tolerance and insulin resistance were analyzed. Pro-inflammatory and anti-inflammatory cytokines were evaluated in serum and skeletal muscle. Skeletal muscle was also processed to estimate mitochondrial function, efficiency, and dynamics, oxidative stress, and antioxidant/detoxifying enzyme activities. Fatty acid profiles, endocannabinoids, and N-acylethanolamine congeners were determined in liver and skeletal muscle tissue.Results: We demonstrated that DM or HM administration reducing inflammation status, improves glucose disposal and insulin resistance and reduces lipid accumulation in skeletal muscle. Moreover, HM or DM administration increases redox status, and mitochondrial uncoupling, affecting mitochondrial dynamics in the skeletal muscle. Interestingly, HM and DM supplementation increase liver and muscle levels of the N-oleoylethanolamine (OEA, a key regulator of lipid metabolism and inflammation.Conclusions: HM and DM have a healthy nutritional effect, acting on inflammatory factors and glucose and lipid metabolism. This beneficial effect is associated to a modulation of

  7. Irreducible Specht modules are signed Young modules

    OpenAIRE

    Hemmer, David J.

    2005-01-01

    Recently Donkin defined signed Young modules as a simultaneous generalization of Young and twisted Young modules for the symmetric group. We show that in odd characteristic, if a Specht module $S^\\lambda$ is irreducible, then $S^\\lambda$ is a signed Young module. Thus the set of irreducible Specht modules coincides with the set of irreducible signed Young modules. This provides evidence for our conjecture that the signed Young modules are precisely the class of indecomposable self-dual module...

  8. Negative voltage modulated multi-level resistive switching by using a Cr/BaTiOx/TiN structure and quantum conductance through evidence of H2O2 sensing mechanism.

    Science.gov (United States)

    Chakrabarti, Somsubhra; Ginnaram, Sreekanth; Jana, Surajit; Wu, Zong-Yi; Singh, Kanishk; Roy, Anisha; Kumar, Pankaj; Maikap, Siddheswar; Qiu, Jian-Tai; Cheng, Hsin-Ming; Tsai, Ling-Na; Chang, Ya-Ling; Mahapatra, Rajat; Yang, Jer-Ren

    2017-07-05

    Negative voltage modulated multi-level resistive switching with quantum conductance during staircase-type RESET and its transport characteristics in Cr/BaTiO x /TiN structure have been investigated for the first time. The as-deposited amorphous BaTiO x film has been confirmed by high-resolution transmission electron microscopy. X-ray photo-electron spectroscopy shows different oxidation states of Ba in the switching material, which is responsible for tunable more than 10 resistance states by varying negative stop voltage owing to slow decay value of RESET slope (217.39 mV/decade). Quantum conductance phenomenon has been observed in staircase RESET cycle of the memory devices. By inspecting the oxidation states of Ba + and Ba 2+ through measuring H 2 O 2 with a low concentration of 1 nM in electrolyte/BaTiO x /SiO 2 /p-Si structure, the switching mechanism of each HRS level as well as the multi-level phenomenon has been explained by gradual dissolution of oxygen vacancy filament. Along with negative stop voltage modulated multi-level, current compliance dependent multi-level has also been demonstrated and resistance ratio up to 2000 has been achieved even for a thin (voltage switching curve has been simulated as well. Hence, multi-level resistive switching of Cr/BaTiO x /TiN structure implies the promising applications in high dense, multistate non-volatile memories in near future.

  9. Modulation of selenium tissue distribution and selenoprotein expression in Atlantic salmon (Salmo salar L.) fed diets with graded levels of plant ingredients.

    Science.gov (United States)

    Betancor, Monica B; Dam, Thi M C; Walton, James; Morken, Thea; Campbell, Patrick J; Tocher, Douglas R

    2016-04-01

    Increased substitution of marine ingredients by terrestrial plant products in aquafeeds has been proven to be suitable for Atlantic salmon farming. However, a reduction in n-3 long-chain PUFA is a consequence of this substitution. In contrast, relatively little attention has been paid to the effects of fishmeal and oil substitution on levels of micronutrients such as Se, considering fish are major sources of this mineral for human consumers. To evaluate the effects of dietary marine ingredient substitution on tissue Se distribution and the expression of Se metabolism and antioxidant enzyme genes, Atlantic salmons were fed three feeds based on commercial formulations with increasing levels of plant proteins (PP) and vegetable oil. Lipid content in flesh did not vary at any sampling point, but it was higher in the liver of 1 kg of fish fed higher PP. Fatty acid content reflected dietary input and was related to oxidation levels (thiobarbituric acid-reactive substances). Liver had the highest Se levels, followed by head kidney, whereas the lowest contents were found in brain and gill. The Se concentration of flesh decreased considerably with high levels of substitution, reducing the added value of fish consumption. Only the brain showed significant differences in glutathione peroxidase, transfer RNA selenocysteine 1-associated protein 1b and superoxide dismutase expression, whereas no significant regulation of Se-related genes was found in liver. Although Se levels in the diets satisfied the essential requirements of salmon, high PP levels led to a reduction in the supply of this essential micronutrient.

  10. Quantification of extracellular levels of corticosterone in the basolateral amygdaloid complex of freely-moving rats: a dialysis study of circadian variation and stress-induced modulation.

    Science.gov (United States)

    Bouchez, Gaëlle; Millan, Mark J; Rivet, Jean-Michel; Billiras, Rodolphe; Boulanger, Raphaël; Gobert, Alain

    2012-05-03

    Corticosterone influences emotion and cognition via actions in a diversity of corticolimbic structures, including the amygdala. Since extracellular levels of corticosterone in brain have rarely been studied, we characterized a specific and sensitive enzymatic immunoassay for microdialysis quantification of corticosterone in the basolateral amygdaloid complex of freely-moving rats. Corticosterone levels showed marked diurnal variation with an evening (dark phase) peak and stable, low levels during the day (light phase). The "anxiogenic agents", FG7142 (20 mg/kg) and yohimbine (10 mg/kg), and an environmental stressor, 15-min forced-swim, induced marked and sustained (1-3 h) increases in dialysis levels of corticosterone in basolateral amygdaloid complex. They likewise increased dialysis levels of dopamine and noradrenaline, but not serotonin and GABA. As compared to basal corticosterone levels of ~200-300 pg/ml, the elevation provoked by forced-swim was ca. 20-fold and this increase was abolished by adrenalectomy. Interestingly, stress-induced rises of corticosterone levels in basolateral amygdaloid complex were abrogated by combined but not separate administration of the corticotrophin releasing factor(1) (CRF(1)) receptor antagonist, CP154,526, and the vasopressin(1b) (V(1b)) receptor antagonist, SSR149,415. Underpinning their specificity, they did not block forced-swim-induced elevations in dopamine and noradrenaline. In conclusion, extracellular levels of corticosterone in the basolateral amygdaloid complex display marked diurnal variation. Further, they are markedly elevated by acute stressors, the effects of which are mediated (in contrast to concomitant elevations in levels of monoamines) by co-joint recruitment of CRF(1) and V(1b) receptors. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Melatonin may play a role in modulation of bax and bcl-2 expression levels to protect rat peripheral blood lymphocytes from gamma irradiation-induced apoptosis

    International Nuclear Information System (INIS)

    Mohseni, Mehran; Mihandoost, Ehsan; Shirazi, Alireza; Sepehrizadeh, Zargham; Bazzaz, Javad Tavakkoly; Ghazi-khansari, Mahmoud

    2012-01-01

    The close relationship between free radicals effects and apoptosis process has been proved. Melatonin has been reported as a direct free radical scavenger. We investigated the capability of melatonin in the modification of radiation-induced apoptosis and apoptosis-associated upstream regulators expression in rat peripheral blood lymphocytes. Rats were irradiated with a single whole body Cobalt 60-gamma radiation dose of 8 Gy at a dose rate of 101 cGy/min with or without melatonin pretreatments at different concentrations of 10 and 100 mg/kg body weight. The rats were divided into eight groups of control, irradiation-only, vehicle-only, vehicle plus irradiation, 10 mg/kg melatonin alone, 10 mg/kg melatonin plus irradiation, 100 mg/kg melatonin alone and 100 mg/kg melatonin plus irradiation. Rats were given an intraperitoneal (IP) injection of melatonin or the same volume of vehicle alone 1 h prior to irradiation. Blood samples were taken 4, 24, 48 and 72 h after irradiation for evaluation of flow cytometric analysis of apoptotic lymphocytes using Annexin V/PI assay and measurement of bax and bcl-2 expression using quantitative real-time PCR (RT 2 qPCR). Irradiation-only and vehicle plus irradiation showed an increase in the percentage of apoptotic lymphocytes significantly different from control group (P < 0.01), while melatonin pretreatments in a dose-dependent manner reduced it as compared with the irradiation-only and vehicle plus irradiation groups (P < 0.01) in all time points. This reduced apoptosis by melatonin was related to the downregulation of bax, upregulation of bcl-2, and therefore reduction of bax/bcl-2 ratio. Our results suggest that melatonin in these doses may provide modulation of bax and bcl-2 expression as well as bax/bcl-2 ratio to protect rat peripheral blood lymphocytes from gamma irradiation-induced apoptosis.

  12. Melatonin may play a role in modulation of bax and bcl-2 expression levels to protect rat peripheral blood lymphocytes from gamma irradiation-induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Mohseni, Mehran [Department of Radiology and Medical Physics, Faculty of Paramedicine, Kashan University of Medical Sciences, Kashan (Iran, Islamic Republic of); Mihandoost, Ehsan, E-mail: mihandoost.e@gmail.com [Department of Medical Radiation Engineering, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Shirazi, Alireza [Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Sepehrizadeh, Zargham [Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Bazzaz, Javad Tavakkoly [Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Ghazi-khansari, Mahmoud [Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2012-10-15

    The close relationship between free radicals effects and apoptosis process has been proved. Melatonin has been reported as a direct free radical scavenger. We investigated the capability of melatonin in the modification of radiation-induced apoptosis and apoptosis-associated upstream regulators expression in rat peripheral blood lymphocytes. Rats were irradiated with a single whole body Cobalt 60-gamma radiation dose of 8 Gy at a dose rate of 101 cGy/min with or without melatonin pretreatments at different concentrations of 10 and 100 mg/kg body weight. The rats were divided into eight groups of control, irradiation-only, vehicle-only, vehicle plus irradiation, 10 mg/kg melatonin alone, 10 mg/kg melatonin plus irradiation, 100 mg/kg melatonin alone and 100 mg/kg melatonin plus irradiation. Rats were given an intraperitoneal (IP) injection of melatonin or the same volume of vehicle alone 1 h prior to irradiation. Blood samples were taken 4, 24, 48 and 72 h after irradiation for evaluation of flow cytometric analysis of apoptotic lymphocytes using Annexin V/PI assay and measurement of bax and bcl-2 expression using quantitative real-time PCR (RT{sup 2}qPCR). Irradiation-only and vehicle plus irradiation showed an increase in the percentage of apoptotic lymphocytes significantly different from control group (P < 0.01), while melatonin pretreatments in a dose-dependent manner reduced it as compared with the irradiation-only and vehicle plus irradiation groups (P < 0.01) in all time points. This reduced apoptosis by melatonin was related to the downregulation of bax, upregulation of bcl-2, and therefore reduction of bax/bcl-2 ratio. Our results suggest that melatonin in these doses may provide modulation of bax and bcl-2 expression as well as bax/bcl-2 ratio to protect rat peripheral blood lymphocytes from gamma irradiation-induced apoptosis.

  13. Signed Young Modules and Simple Specht Modules

    OpenAIRE

    Danz, Susanne; Lim, Kay Jin

    2015-01-01

    By a result of Hemmer, every simple Specht module of a finite symmetric group over a field of odd characteristic is a signed Young module. While Specht modules are parametrized by partitions, indecomposable signed Young modules are parametrized by certain pairs of partitions. The main result of this article establishes the signed Young module labels of simple Specht modules. Along the way we prove a number of results concerning indecomposable signed Young modules that are of independent inter...

  14. Modulation of cAMP levels by high-fat diet and curcumin and regulatory effects on CD36/FAT scavenger receptor/fatty acids transporter gene expression.

    Science.gov (United States)

    Zingg, Jean-Marc; Hasan, Syeda T; Nakagawa, Kiyotaka; Canepa, Elisa; Ricciarelli, Roberta; Villacorta, Luis; Azzi, Angelo; Meydani, Mohsen

    2017-01-02

    Curcumin, a polyphenol from turmeric (Curcuma longa), reduces inflammation, atherosclerosis, and obesity in several animal studies. In Ldlr -/- mice fed a high-fat diet (HFD), curcumin reduces plasma lipid levels, therefore contributing to a lower accumulation of lipids and to reduced expression of fatty acid transport proteins (CD36/FAT, FABP4/aP2) in peritoneal macrophages. In this study, we analyzed the molecular mechanisms by which curcumin (500, 1000, 1500 mg/kg diet, for 4 months) may influence plasma and tissue lipid levels in Ldlr -/- mice fed an HFD. In liver, HFD significantly suppressed cAMP levels, and curcumin restored almost normal levels. Similar trends were observed in adipose tissues, but not in brain, skeletal muscle, spleen, and kidney. Treatment with curcumin increased phosphorylation of CREB in liver, what may play a role in regulatory effects of curcumin in lipid homeostasis. In cell lines, curcumin increased the level of cAMP, activated the transcription factor CREB and the human CD36 promoter via a sequence containing a consensus CREB response element. Regulatory effects of HFD and Cur on gene expression were observed in liver, less in skeletal muscle and not in brain. Since the cAMP/protein kinase A (PKA)/CREB pathway plays an important role in lipid homeostasis, energy expenditure, and thermogenesis by increasing lipolysis and fatty acid β-oxidation, an increase in cAMP levels induced by curcumin may contribute to its hypolipidemic and anti-atherosclerotic effects. © 2016 BioFactors, 43(1):42-53, 2017. © 2016 International Union of Biochemistry and Molecular Biology.

  15. Memory Modulation

    NARCIS (Netherlands)

    Roozendaal, Benno; McGaugh, James L.

    2011-01-01

    Our memories are not all created equally strong: Some experiences are well remembered while others are remembered poorly, if at all. Research on memory modulation investigates the neurobiological processes and systems that contribute to such differences in the strength of our memories. Extensive

  16. Module descriptor

    DEFF Research Database (Denmark)

    Vincenti, Gordon; Klausen, Bodil; Kjær Jensen, Jesper

    2016-01-01

    The Module Descriptor including a Teacher’s Guide explains and describes how to work innovatively and co-creatively with wicked problems and young people. The descriptor shows how interested educators and lecturers in Europe can copy the lessons of the Erasmus+ project HIP when teaching their own...

  17. Modulation by geraniol of gene expression involved in lipid metabolism leading to a reduction of serum-cholesterol and triglyceride levels.

    Science.gov (United States)

    Galle, Marianela; Kladniew, Boris Rodenak; Castro, María Agustina; Villegas, Sandra Montero; Lacunza, Ezequiel; Polo, Mónica; de Bravo, Margarita García; Crespo, Rosana

    2015-07-15

    Geraniol (G) is a natural isoprenoid present in the essential oils of several aromatic plants, with various biochemical and pharmacologic properties. Nevertheless, the mechanisms of action of G on cellular metabolism are largely unknown. We propose that G could be a potential agent for the treatment of hyperlipidemia that could contribute to the prevention of cardiovascular disease. The aim of the present study was to advance our understanding of its mechanism of action on cholesterol and TG metabolism. NIH mice received supplemented diets containing 25, 50, and 75 mmol G/kg chow. After a 3-week treatment, serum total-cholesterol and triglyceride levels were measured by commercial kits and lipid biosynthesis determined by the [(14)C] acetate incorporated into fatty acids plus nonsaponifiable and total hepatic lipids of the mice. The activity of the mRNA encoding HMGCR-the rate-limiting step in cholesterol biosynthesis-along with the enzyme levels and catalysis were assessed by real-time RT-PCR, Western blotting, and HMG-CoA-conversion assays, respectively. In-silico analysis of several genes involved in lipid metabolism and regulated by G in cultured cells was also performed. Finally, the mRNA levels encoded by the genes for the low-density-lipoprotein receptor (LDLR), the sterol-regulatory-element-binding transcription factor (SREBF2), the very-low-density-lipoprotein receptor (VLDLR), and the acetyl-CoA carboxylase (ACACA) were determined by real-time RT-PCR. Plasma total-cholesterol and triglyceride levels plus hepatic fatty-acid, total-lipid, and nonsaponifiable-lipid biosynthesis were significantly reduced by feeding with G. Even though an up-regulation of the mRNA encoding HMGCR occurred in the G treated mouse livers, the protein levels and specific activity of the enzyme were both inhibited. G also enhanced the mRNAs encoding the LDL and VLDL receptors and reduced ACACA mRNA, without altering the transcription of the mRNA encoding the SREBF2. The following

  18. Effect of dopamine, dopamine D-1 and D-2 receptor modulation on ACTH and cortisol levels in normal men and women

    DEFF Research Database (Denmark)

    Boesgaard, S; Hagen, C; Andersen, A N

    1990-01-01

    The regulation of the hypothalamic-pituitary-adrenal axis by dopamine is not fully understood. Therefore, we have studied the effect of dopamine, metoclopramide, a D-2 receptor antagonist, and fenoldopam, a specific D-1 receptor agonist, on ACTH and cortisol levels in normal subjects. Normal women...

  19. Adaptor protein containing PH domain, PTB domain and leucine zipper (APPL1) regulates the protein level of EGFR by modulating its trafficking

    International Nuclear Information System (INIS)

    Lee, Jae-Rin; Hahn, Hwa-Sun; Kim, Young-Hoon; Nguyen, Hong-Hoa; Yang, Jun-Mo; Kang, Jong-Sun; Hahn, Myong-Joon

    2011-01-01

    Highlights: ► APPL1 regulates the protein level of EGFR in response to EGF stimulation. ► Depletion of APPL1 accelerates the movement of EGF/EGFR from the cell surface to the perinuclear region in response to EGF. ► Knockdown of APPL1 enhances the activity of Rab5. -- Abstract: The EGFR-mediated signaling pathway regulates multiple biological processes such as cell proliferation, survival and differentiation. Previously APPL1 (adaptor protein containing PH domain, PTB domain and leucine zipper 1) has been reported to function as a downstream effector of EGF-initiated signaling. Here we demonstrate that APPL1 regulates EGFR protein levels in response to EGF stimulation. Overexpression of APPL1 enhances EGFR stabilization while APPL1 depletion by siRNA reduces EGFR protein levels. APPL1 depletion accelerates EGFR internalization and movement of EGF/EGFR from cell surface to the perinuclear region in response to EGF treatment. Conversely, overexpression of APPL1 decelerates EGFR internalization and translocation of EGF/EGFR to the perinuclear region. Furthermore, APPL1 depletion enhances the activity of Rab5 which is involved in internalization and trafficking of EGFR and inhibition of Rab5 in APPL1-depleted cells restored EGFR levels. Consistently, APPL1 depletion reduced activation of Akt, the downstream signaling effector of EGFR and this is restored by inhibition of Rab5. These findings suggest that APPL1 is required for EGFR signaling by regulation of EGFR stabilities through inhibition of Rab5.

  20. Modulation of total IgE levels in serum of normal and athymic nude BALB/c mice by cells and exogenous antigenic stimulation

    NARCIS (Netherlands)

    Savelkoul, H.F.J.; Akker, van den T.W.; Soeting, P.W.C.; Oudenaren, van A.; Benner, R.

    1989-01-01

    Several different grades of T-system impairment were studied for their effects on the total serum IgE concentration in BALB/c mice. Homozygous athymic nu/nu mice and their heterozygous nu/ littermates were compared for serum IgE levels while kept under either barrier-maintained or conventional

  1. CHOLINERGIC AND NORADRENERGIC MODULATION OF LONG-TERM EXPLICIT MEMORY ARE ALTERED BY CHRONIC LOW-LEVEL LEAD EXPOSURE. (U915393)

    Science.gov (United States)

    Recent evidence suggests that septohippocampal cholinergic activity is suppressed in rats exposed to low levels of lead (Pb). As a result, noradrenergic activity may be elevated due to compensatory sympathetic sprouting. Therefore, the goals of this study were to (a) determine...

  2. Modulation of cAMP levels by high fat diet and curcumin and regulatory effects on CD36/FAT scavenger receptor/fatty acids transporter gene expression

    Science.gov (United States)

    Curcumin, a polyphenol from turmeric (Curcuma longa), reduces inflammation, atherosclerosis, and obesity in several animal studies. In Ldlr-/- mice fed a high-fat diet (HFD), curcumin reduces plasma lipid levels, therefore contributing to a lower accumulation of lipids and to reduced expression of f...

  3. Protein-induced fusion can be modulated by target membrane lipids through a structural switch at the level of the fusion peptide

    NARCIS (Netherlands)

    Pecheur, EI; Martin, [No Value; Bienvenue, A; Ruysschaert, JM; Hoekstra, D

    2000-01-01

    Regulatory features of protein-induced membrane fusion are largely unclear, particularly at the level of the fusion peptide. Fusion peptides being part of larger protein complexes, such investigations are met with technical limitations. Here, we show that the fusion activity of influenza virus or

  4. Adiposity associated changes in serum glucose and adiponectin levels modulate ovarian steroidogenesis during delayed embryonic development in the fruit bat, Cynopterus sphinx.

    Science.gov (United States)

    Anuradha; Krishna, Amitabh

    2018-06-01

    The aim of the present study was to evaluate the mechanism by which embryonic development in Cynopterus sphinx is impaired during the period of increased accumulation of white adipose tissue during winter scarcity of food. The change in the mass of white adipose tissue during adipogenesis showed significant positive correlation with the circulating glucose level. But increase in circulating glucose level during the adipogenesis showed negative correlation with circulating progesterone and adiponectin levels. The in vivo study showed increased glucose uptake by the adipose tissue during adipogenesis due to increased expression of insulin receptor (IR) and glucose transporter (GLUT) 4 proteins. This study showed decline in the adiponectin level during fat accumulation. In the in vitro study, ovary treated with high doses of glucose showed impaired progesterone synthesis. This is due to decreased glucose uptake mediated decrease in the expression of luteinizing hormone-receptor, steroidogenic acute regulatory protein, IR, GLUT4 and AdipoR1 proteins. But the ovary treated with adiponectin either alone or with higher concentration of glucose showed improvement in progesterone synthesis due to increased expression of IR, GLUT4 and AdipoR1 mediated increased glucose uptake. In conclusion, increased circulating glucose level prior to winter dormancy preferably transported to white adipose tissue for fat accumulation diverting glucose away from the ovary. Consequently the decreased availability of adiponectin and glucose to the ovary and utero-embryonic unit may be responsible for impaired progesterone synthesis and delayed embryonic development. The delayed embryonic development in Cynopterus sphinx may have evolved, in part, as a mechanism to prevent pregnancy loss during the period of decreased energy availability. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Modifications of Western-type diet regarding protein, fat and sucrose levels as modulators of steroid metabolism and activity in liver.

    Science.gov (United States)

    Krawczyńska, Agata; Herman, Andrzej P; Antushevich, Hanna; Bochenek, Joanna; Dziendzikowska, Katarzyna; Gajewska, Alina; Gromadzka-Ostrowska, Joanna

    2017-01-01

    The aim of the study was to evaluate whether the modification of the Western-type diet (high-fat, high-sucrose diet rich in saturated fatty acids) considering macronutrients content would influence hepatic metabolism and activity of steroids. For 3 weeks Wistar rat were fed the Western-type diet (21% fat, 35% sucrose, 19% protein, lard) and its modifications regarding dietary protein (10 and 19%), fat (5 and 21%) and sucrose (0 and 35%) levels. The steroid 5α-reductase type 1 (Srd5a1) and androgen receptor (Ar) gene expression as well as testosterone (T) conversion towards 5α-reduced derivatives in liver were positively correlated with body weight gain. The Western-type diets with decreased protein content regardless of the sucrose level exerted the most negative effect on the antioxidant system decreasing catalase (Cat), sodium dismutase (Sod1) and glutathione peroxidase (Gpx1) gene expression as well as Cat and Gpx activity and total antioxidant status, simultaneously intensifying lipid peroxidation. The impaired antioxidant system was accompanied by decreased level of hepatic T metabolism towards estrogens: 17β-estradiol (E2) and estriol, and increased estrogen receptor type 1 (Esr1) gene expression. Liver Esr1 mRNA level was differently correlated with T (positively) and E2 (negatively) plasma levels. Whereas the fat reduction in Western-type diet restored the plasma proportion between T and E2. In conclusion it could be stated that Western-type diet modification relating to protein, sucrose and fat content can influence hepatic steroid metabolism and activity; however the estrogens and androgens metabolism in liver would be connected with impairment of liver function or catabolic activity, respectively. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Space Experiment Module (SEM)

    Science.gov (United States)

    Brodell, Charles L.

    1999-01-01

    The Space Experiment Module (SEM) Program is an education initiative sponsored by the National Aeronautics and Space Administration (NASA) Shuttle Small Payloads Project. The program provides nationwide educational access to space for Kindergarten through University level students. The SEM program focuses on the science of zero-gravity and microgravity. Within the program, NASA provides small containers or "modules" for students to fly experiments on the Space Shuttle. The experiments are created, designed, built, and implemented by students with teacher and/or mentor guidance. Student experiment modules are flown in a "carrier" which resides in the cargo bay of the Space Shuttle. The carrier supplies power to, and the means to control and collect data from each experiment.

  7. Acute effects of nitroglycerin depend on both plasma and intracellular sulfhydryl compound levels in vivo. Effect of agents with different sulfhydryl-modulating properties

    DEFF Research Database (Denmark)

    Boesgaard, S; Poulsen, H E; Aldershvile, J

    1993-01-01

    in SH group concentrations (cysteine and glutathione [GSH]) affect the responsiveness to NTG in vivo. METHODS AND RESULTS: GSH and cysteine levels in plasma, vena cava, and aorta were measured after administration of N-acetylserine (placebo, n = 6), N-acetylcysteine (NAC, extracellular and intracellular......BACKGROUND: Changes in sulfhydryl (SH) compound availability may alter the hemodynamic effect of nitroglycerin (NTG). Data on the relation between NTG effect and thiol levels are, however, limited to in vitro experiments. The present study investigates how intracellular and extracellular changes...... SH donor, n = 6), oxothiazolidine (OXO, intracellular SH donor, n = 6), buthionine sulfoximine (BSO, intracellular GSH-depleting agent, n = 6), BSO+NAC (n = 6), and BSO+OXO (n = 6) in chronically catheterized conscious rats. In addition, the effect of 2.5 mg NTG/kg i.v. on mean arterial pressure (MAP...

  8. Active and passive sexual roles that arise in Drosophila male-male courtship are modulated by dopamine levels in PPL2ab neurons

    OpenAIRE

    Shiu-Ling Chen; Yu-Hui Chen; Chuan-Chan Wang; Yhu-Wei Yu; Yu-Chen Tsai; Hsiao-Wen Hsu; Chia-Lin Wu; Pei-Yu Wang; Lien-Cheng Chen; Tsuo-Hung Lan; Tsai-Feng Fu

    2017-01-01

    The neurology of male sexuality has been poorly studied owing to difficulties in studying brain circuitry in humans. Dopamine (DA) is essential for both physiological and behavioural responses, including the regulation of sexuality. Previous studies have revealed that alterations in DA synthesis in dopaminergic neurons can induce male-male courtship behaviour, while increasing DA levels in the protocerebral posteriolateral dopaminergic cluster neuron 2ab (PPL2ab) may enhance the intensity of ...

  9. F7 gene variants modulate protein levels in a large cohort of patients with factor VII deficiency. Results from a genotype-phenotype study.

    Science.gov (United States)

    Quintavalle, Gabriele; Riccardi, Federica; Rivolta, Gianna Franca; Martorana, Davide; Di Perna, Caterina; Percesepe, Antonio; Tagliaferri, Annarita

    2017-08-01

    Congenital factor VII (FVII) deficiency is a rare bleeding disorder caused by mutations in F7 gene with autosomal recessive inheritance. A clinical heterogeneity with poor correlation with FVII:C levels has been described. It was the objective of this study to identify genetic defects and to evaluate their relationships with phenotype in a large cohort of patients with FVII:C<50 %. One hundred twenty-three probands were genotyped for F7 mutations and three polymorphic variants and classified according to recently published clinical scores. Forty out of 123 patients (33 %) were symptomatic (43 bleedings). A severe bleeding tendency was observed only in patients with FVII:C<0.10 %. Epistaxis (11 %) and menorrhagia (32 % of females in fertile age) were the most frequent bleedings. Molecular analysis detected 48 mutations, 20 not reported in the F7 international databases. Most mutations (62 %) were missense, large deletions were 6.2 %. Compound heterozygotes/homozygotes for mutations presented lower FVII:C levels compared to the other classes (Chi 2 =43.709, p<0,001). The polymorphisms distribution was significantly different among the three F7 genotypic groups (Chi 2 =72.289, p<0,001). The presence of truncating mutations was associated with lowest FVII:C levels (Chi 2 =21.351, p=0.002). This study confirms the clinical and molecular variability of the disease and the type of symptoms. It shows a good correlation between the type of F7 mutation and/or polymorphisms and FVII:C levels, without a direct link between FVII:C and bleeding tendency. The results suggest that large deletions are underestimated and that they represent a common mechanism of F7 gene inactivation which should always be investigated in the diagnostic testing for FVII deficiency.

  10. Gender and genotype modulation of the association between lipid levels and depressive symptomatology in community-dwelling elderly (the ESPRIT study).

    Science.gov (United States)

    Ancelin, Marie-Laure; Carrière, Isabelle; Boulenger, Jean-Philippe; Malafosse, Alain; Stewart, Robert; Cristol, Jean-Paul; Ritchie, Karen; Chaudieu, Isabelle; Dupuy, Anne-Marie

    2010-07-15

    Lipids appear to mediate depressive vulnerability in the elderly; however, sex differences and genetic vulnerability have not been taken into account in previous prospective studies. Depression was assessed in a population of 1040 women and 752 men aged 65 years and older at baseline and after 7-year follow-up. Clinical level of depression (DEP) was defined as having either a score of 16 or higher on the Centre for Epidemiology Studies Depression scale or a diagnosis of current major depression on the Mini-International Neuropsychiatric Interview. Lipid levels, apolipoprotein E, and serotonin transporter linked promoter region (5-serotonin transporter gene linked promoter region) genotypes were evaluated at baseline. Multivariate analyses adjusted by sociodemographic and behavioral variables, measures of physical health including ischemic pathologies, and genetic vulnerability indicated gender-specific associations between dyslipidemia and DEP, independent of the use of lipid-lowering agents or apolipoprotein E status. Men with low low-density lipoprotein cholesterol levels had twice the risk of prevalent and incident DEP, whereas in women low high-density lipoprotein cholesterol levels were found to be significantly associated with increased prevalent DEP (odds ratio = 1.5) only. A significant interaction was observed between low low-density lipoprotein-cholesterol and 5-serotonin transporter gene linked promoter region genotype, men with s/s or s/l genotype being at increased risk of DEP (odds ratio = 6.0 and 2.7, respectively). No significant gene-environment interaction was observed for women. DEP is associated with higher atherogenic risk in women (low high-density lipoprotein cholesterol), whereas the reverse is observed in men (low low-density lipoprotein cholesterol). Late-life depression may have a complex gender-specific etiology involving genetic vulnerability in men. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights

  11. Modulation of DNA repair capacity and mRNA expression levels of XRCC1, hOGG1 and XPC genes in styrene-exposed workers

    International Nuclear Information System (INIS)

    Hanova, Monika; Stetina, Rudolf; Vodickova, Ludmila; Vaclavikova, Radka; Hlavac, Pavel; Smerhovsky, Zdenek; Naccarati, Alessio; Polakova, Veronika; Soucek, Pavel; Kuricova, Miroslava; Manini, Paola; Kumar, Rajiv; Hemminki, Kari; Vodicka, Pavel

    2010-01-01

    Decreased levels of single-strand breaks in DNA (SSBs), reflecting DNA damage, have previously been observed with increased styrene exposure in contrast to a dose-dependent increase in the base-excision repair capacity. To clarify further the above aspects, we have investigated the associations between SSBs, micronuclei, DNA repair capacity and mRNA expression in XRCC1, hOGG1 and XPC genes on 71 styrene-exposed and 51 control individuals. Styrene concentrations at workplace and in blood characterized occupational exposure. The workers were divided into low (below 50 mg/m 3 ) and high (above 50 mg/m 3 ) styrene exposure groups. DNA damage and DNA repair capacity were analyzed in peripheral blood lymphocytes by Comet assay. The mRNA expression levels were determined by qPCR. A significant negative correlation was observed between SSBs and styrene concentration at workplace (R = - 0.38, p = 0.001); SSBs were also significantly higher in men (p = 0.001). The capacity to repair irradiation-induced DNA damage was the highest in the low exposure group (1.34 ± 1.00 SSB/10 9 Da), followed by high exposure group (0.72 ± 0.81 SSB/10 9 Da) and controls (0.65 ± 0.82 SSB/10 9 Da). The mRNA expression levels of XRCC1, hOGG1 and XPC negatively correlated with styrene concentrations in blood and at workplace (p < 0.001) and positively with SSBs (p < 0.001). Micronuclei were not affected by styrene exposure, but were higher in older persons and in women (p < 0.001). In this study, we did not confirm previous findings on an increased DNA repair response to styrene-induced genotoxicity. However, negative correlations of SSBs and mRNA expression levels of XRCC1, hOGG1 and XPC with styrene exposure warrant further highly-targeted study.

  12. Effects of resveratrol, grape juice or red wine consumption Irisin levels and fibronectin type III domain containing protein 5 and uncoupoling protein gene expression modulation in rats

    Directory of Open Access Journals (Sweden)

    Gabrielle de Souza Rocha

    2016-02-01

    Conclusion: Resveratrol and grape juice were able to increase muscle tissue FNDC5 gene expression, and high-fat diet, red wine and resveratrol, increased UCP2 gene expression in this tissue. Grape juice was capable of increasing adipose tissue UCP2 gene expression. High-fat diet, isolated or associated to beverages rich in polyphenols, have decreased FNDC5 gene expression in adipose tissue. Nevertheless, the interventions did not affect irisin levels.

  13. Bis(phenylimidazoselenazolyl) diselenide elicits antinociceptive effect by modulating myeloperoxidase activity, NOx and NFkB levels in the collagen-induced arthritis mouse model.

    Science.gov (United States)

    Chagas, Pietro M; Fulco, Bruna C W; Sari, Marcel H M; Roehrs, Juliano A; Nogueira, Cristina W

    2017-08-01

    Bis(phenylimidazoselenazolyl) diselenide (BPIS) is an organoselenium with acute antinociceptive and antioxidant properties. The aim of this study was to investigate BPIS effect on a collagen-induced arthritis (CIA) model in mice. Protocol of exposure consisted in arthritis induction by chicken collagen type II on day 0 with booster injection on day 21. On day 60 after collagen injection, incidence of mechanic allodynia (Von Frey test) or thermal hyperalgesia (hot plate test) was evaluated. During following 5 days, mice were treated with BPIS (0.1-1 mg/kg; p.o.; daily) or vehicle. On day 65, mice were killed, and paws and spinal cord were removed for analyses. Mice submitted to CIA model developed both mechanical allodynia and thermal hyperalgesia, which were reversed by BPIS at the highest dose. In paw, BPIS reversed the increase in myeloperoxidase activity in the CIA group. In the spinal cord, BPIS decreased NOx and NFkB levels increased in the CIA group. BPIS-treated animals had lower cyclooxygenase-2 levels in the spinal cord. The myeloperoxidase activity in paw and NOx and NFkB levels in spinal cord are related to antinociceptive properties of BPIS in CIA model. © 2017 Royal Pharmaceutical Society.

  14. Bunch identification module

    International Nuclear Information System (INIS)

    Fox, J.D.

    1981-01-01

    This module provides bunch identification and timing signals for the PEP Interaction areas. Timing information is referenced to the PEP master oscillator, and adjusted in phase as a function of region. Identification signals are generated in a manner that allows observers in all interaction regions to agree on an unambiguous bunch identity. The module provides bunch identification signals via NIM level logic, upon CAMAC command, and through LED indicators. A front panel ''region select'' switch allows the same module to be used in all regions. The module has two modes of operation: a bunch identification mode and a calibration mode. In the identification mode, signals indicate which of the three bunches of electrons and positrons are interacting, and timing information about beam crossing is provided. The calibration mode is provided to assist experimenters making time of flight measurements. In the calibration mode, three distinct gating signals are referenced to a selected bunch, allowing three timing systems to be calibrated against a common standard. Physically, the bunch identifier is constructed as a single width CAMAC module. 2 figs., 1 tab

  15. Reduced sTWEAK and increased sCD163 levels in HIV-infected patients: modulation by antiretroviral treatment, HIV replication and HCV co-infection.

    Directory of Open Access Journals (Sweden)

    Luis M Beltrán

    Full Text Available Patients infected with the human immunodeficiency virus (HIV have an increased risk of cardiovascular disease due to increased inflammation and persistent immune activation. CD163 is a macrophage scavenger receptor that is involved in monocyte-macrophage activation in HIV-infected patients. CD163 interacts with TWEAK, a member of the TNF superfamily. Circulating levels of sTWEAK and sCD163 have been previously associated with cardiovascular disease, but no previous studies have fully analyzed their association with HIV.The aim of this study was to analyze circulating levels of sTWEAK and sCD163 as well as other known markers of inflammation (hsCRP, IL-6 and sTNFRII and endothelial dysfunction (sVCAM-1 and ADMA in 26 patients with HIV before and after 48 weeks of antiretroviral treatment (ART and 23 healthy subjects.Patients with HIV had reduced sTWEAK levels and increased sCD163, sVCAM-1, ADMA, hsCRP, IL-6 and sTNFRII plasma concentrations, as well as increased sCD163/sTWEAK ratio, compared with healthy subjects. Antiretroviral treatment significantly reduced the concentrations of sCD163, sVCAM-1, hsCRP and sTNFRII, although they remained elevated when compared with healthy subjects. Antiretroviral treatment had no effect on the concentrations of ADMA and sTWEAK, biomarkers associated with endothelial function. The use of protease inhibitors as part of antiretroviral therapy and the presence of HCV-HIV co-infection and/or active HIV replication attenuated the ART-mediated decrease in sCD163 plasma concentrations.HIV-infected patients showed a proatherogenic profile characterized by increased inflammatory, immune-activation and endothelial-dysfunction biomarkers that partially improved after ART. HCV-HIV co-infection and/or active HIV replication enhanced immune activation despite ART.

  16. Astrocyte sigma-1 receptors modulate connexin 43 expression leading to the induction of below-level mechanical allodynia in spinal cord injured mice.

    Science.gov (United States)

    Choi, Sheu-Ran; Roh, Dae-Hyun; Yoon, Seo-Yeon; Kwon, Soon-Gu; Choi, Hoon-Seong; Han, Ho-Jae; Beitz, Alvin J; Lee, Jang-Hern

    2016-12-01

    We have previously shown using a spinal cord injury (SCI) model that gap junctions contribute to the early spread of astrocyte activation in the lumbar spinal cord and that this astrocyte communication plays critical role in the induction of central neuropathic pain. Sigma-1 receptors (Sig-1Rs) have been implicated in spinal astrocyte activation and the development of peripheral neuropathic pain, yet their contribution to central neuropathic pain remains unknown. Thus, we investigated whether SCI upregulates spinal Sig-1Rs, which in turn increase the expression of the astrocytic gap junction protein, connexin 43 (Cx43) leading to the induction of central neuropathic pain. A thoracic spinal cord hemisection significantly increased both astrocyte activation and Cx43 expression in lumbar dorsal horn. Sig-1Rs were also increased in lumbar dorsal horn astrocytes, but not neurons or microglia. Intrathecal injection of an astrocyte metabolic inhibitor (fluorocitrate); a gap junction/hemichannel blocker (carbenoxolone); or a Cx43 mimetic peptide ( 43 Gap26) significantly reduced SCI-induced bilateral below-level mechanical allodynia. Blockade of Sig-1Rs with BD1047 during the induction phase of pain significantly suppressed the SCI-induced development of mechanical allodynia, astrocyte activation, increased expression of Cx43 in both total and membrane levels, and increased association of Cx43 with Sig-1R. However, SCI did not change the expression of oligodendrocyte (Cx32) or neuronal (Cx36) gap junction proteins. These findings demonstrate that SCI activates astrocyte Sig-1Rs leading to increases in the expression of the gap junction protein, Cx43 and astrocyte activation in the lumbar dorsal horn, and ultimately contribute to the induction of bilateral below-level mechanical allodynia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Express immunochromatographic detection of antibodies against Brucella abortus in cattle sera based on quantitative photometric registration and modulated cut-off level.

    Science.gov (United States)

    Sotnikov, Dmitriy V; Byzova, Nadezhda A; Zherdev, Anatoly V; Eskendirova, Saule Z; Baltin, Kairat K; Mukanov, Kasim K; Ramankulov, Erlan M; Sadykhov, Elchin G; Dzantiev, Boris B

    2015-01-01

    An immunochromatographic test system was developed for rapid detection of the levels of specific IgG antibodies to Brucella abortus lipopolysaccharide, as a tool for diagnosis of brucellosis in cattle. The pilot test strips were examined using blood sera from sick (78 samples) and healthy (35 samples) cows. The results obtained by immunochromatographic assay, using a portable optical densitometer for digital video detection, correlate well with the results obtained by immunoenzyme assay and are in agreement with the results of the disease diagnosis. The new test system allows detection of antibodies within 10 min and can be proposed as an alternative to the methods available for serodiagnosis of brucellosis.

  18. Dlk1/FA1 Is a Novel Endocrine Regulator of Bone and Fat Mass and Its Serum Level Is Modulated By Growth Hormone

    DEFF Research Database (Denmark)

    Abdallah, B.M.; Ding, M.; Jensen, C.H.

    2007-01-01

    Fat and bone metabolism are two linked processes regulated by several hormonal factors. FA1 (fetal antigen 1) is the soluble form of dlk1 (delta like 1), which is a member of the Notch-Delta family. We have previously identified FA1 as a negative regulator of bone marrow mesenchymal stem cell...... differentiation. Here, we studied the effects of circulating FA1 on fat and bone mass in vivo by generating mice expressing high serum levels of FA1 (FA1-mice) using the hydrodynamic-based gene transfer procedure (HGTP). We found that increased serum FA1 levels led to a significant reduction in total body weight......, fat mass and bone mass in a dose-dependent manner. Reduced bone mass in FA1-mice was associated with the inhibition of mineral apposition rate and bone formation rates by 58% and 72% respectively. Since FA1 is co-localized with growth hormone (GH) in the pituitary gland, we explored the possible...

  19. Nonsteroidal Selective Androgen Receptor Modulators and Selective Estrogen Receptor β Agonists Moderate Cognitive Deficits and Amyloid-β Levels in a Mouse Model of Alzheimer’s Disease

    Science.gov (United States)

    2013-01-01

    Decreases of the sex steroids, testosterone and estrogen, are associated with increased risk of Alzheimer’s disease. Testosterone and estrogen supplementation improves cognitive deficits in animal models of Alzheimer’s disease. Sex hormones play a role in the regulation of amyloid-β via induction of the amyloid-β degrading enzymes neprilysin and insulin-degrading enzyme. To mimic the effect of dihydrotestosterone (DHT), we administered a selective androgen receptor agonist, ACP-105, alone and in combination with the selective estrogen receptor β (ERβ) agonist AC-186 to male gonadectomized triple transgenic mice. We assessed long-term spatial memory in the Morris water maze, spontaneous locomotion, and anxiety-like behavior in the open field and in the elevated plus maze. We found that ACP-105 given alone decreases anxiety-like behavior. Furthermore, when ACP-105 is administered in combination with AC-186, they increase the amyloid-β degrading enzymes neprilysin and insulin-degrading enzyme and decrease amyloid-β levels in the brain as well as improve cognition. Interestingly, the androgen receptor level in the brain was increased by chronic treatment with the same combination treatment, ACP-105 and AC-186, not seen with DHT or ACP-105 alone. Based on these results, the beneficial effect of the selective ERβ agonist as a potential therapeutic for Alzheimer’s disease warrants further investigation. PMID:24020966

  20. Folic Acid Supplementation Delays Atherosclerotic Lesion Development by Modulating MCP1 and VEGF DNA Methylation Levels In Vivo and In Vitro

    Science.gov (United States)

    Cui, Shanshan; Li, Wen; Lv, Xin; Wang, Pengyan; Gao, Yuxia; Huang, Guowei

    2017-01-01

    The pathogenesis of atherosclerosis has been partly acknowledged to result from aberrant epigenetic mechanisms. Accordingly, low folate levels are considered to be a contributing factor to promoting vascular disease because of deregulation of DNA methylation. We hypothesized that increasing the levels of folic acid may act via an epigenetic gene silencing mechanism to ameliorate atherosclerosis. Here, we investigated the atheroprotective effects of folic acid and the resultant methylation status in high-fat diet-fed ApoE knockout mice and in oxidized low-density lipoprotein-treated human umbilical vein endothelial cells. We analyzed atherosclerotic lesion histology, folate concentration, homocysteine concentration, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), and DNA methyltransferase activity, as well as monocyte chemotactic protein-1 (MCP1) and vascular endothelial growth factor (VEGF) expression and promoter methylation. Folic acid reduced atherosclerotic lesion size in ApoE knockout mice. The underlying folic acid protective mechanism appears to operate through regulating the normal homocysteine state, upregulating the SAM: SAH ratio, elevating DNA methyltransferase activity and expression, altering MCP1 and VEGF promoter methylation, and inhibiting MCP1 and VEGF expression. We conclude that folic acid supplementation effectively prevented atherosclerosis by modifying DNA methylation through the methionine cycle, improving DNA methyltransferase activity and expression, and thus changing the expression of atherosclerosis-related genes. PMID:28475147

  1. Treatment of grain with organic acids at 2 different dietary phosphorus levels modulates ruminal microbial community structure and fermentation patterns in vitro.

    Science.gov (United States)

    Harder, H; Khol-Parisini, A; Metzler-Zebeli, B U; Klevenhusen, F; Zebeli, Q

    2015-11-01

    Recent data indicate positive effects of treating grain with citric (CAc) or lactic acid (LAc) on the hydrolysis of phytate phosphorus (P) and fermentation products of the grain. This study used a semicontinuous rumen simulation technique to evaluate the effects of processing of barley with 50.25 g/L (wt/vol) CAc or 76.25 g/L LAc on microbial composition, metabolic fermentation profile, and nutrient degradation at low or high dietary P supply. The low P diet [3.1g of P per kg of dry matter (DM) of dietary P sources only] was not supplemented with inorganic P, whereas the high P diet was supplemented with 0.5 g of inorganic P per kg of DM through mineral premix and 870 mg of inorganic P/d per incubation fermenter via artificial saliva. Target microbes were determined using quantitative PCR. Data showed depression of total bacteria but not of total protozoa or short-chain fatty acid (SCFA) concentration with the low P diet. In addition, the low P diet lowered the relative abundance of Ruminococcus albus and decreased neutral detergent fiber (NDF) degradation and acetate proportion, but increased the abundance of several predominantly noncellulolytic bacterial species and anaerobic fungi. Treatment of grain with LAc increased the abundance of total bacteria in the low P diet only, and this effect was associated with a greater concentration of SCFA in the ruminal fluid. Interestingly, in the low P diet, CAc treatment of barley increased the most prevalent bacterial group, the genus Prevotella, in ruminal fluid and increased NDF degradation to the same extent as did inorganic P supplementation in the high P diet. Treatment with either CAc or LAc lowered the abundance of Megasphaera elsdenii but only in the low P diet. On the other hand, CAc treatment increased the proportion of acetate in the low P diet, whereas LAc treatment decreased this variable at both dietary P levels. The propionate proportion was significantly increased by LAc at both P levels, whereas butyrate

  2. ANALYSIS OF HARMONIC INJECTION TO THE MODULATION OF ...

    African Journals Online (AJOL)

    2013-03-01

    Mar 1, 2013 ... Abstract. This paper explores the analysis of third and ninth harmonic injection to the modulation of a multi- level diode clamped converter (DCC) at a varying modulation index. The spectral distributions of the various multi-level waveforms obtained under normal modulation index of 0.8 and over modulation ...

  3. Medical Terminology: Prefixes. Health Occupations Education Module.

    Science.gov (United States)

    Temple Univ., Philadelphia, PA. Div. of Vocational Education.

    This module on medical terminology (prefixes) is one of 17 modules designed for individualized instruction in health occupations education programs at both the secondary and postsecondary levels. This module consists of an introduction to prefixes, a list of resources needed, and three learning experiences. Each learning experience contains an…

  4. Dietary phytic acid modulates characteristics of the colonic luminal environment and reduces serum levels of proinflammatory cytokines in rats fed a high-fat diet.

    Science.gov (United States)

    Okazaki, Yukako; Katayama, Tetsuyuki

    2014-12-01

    Dietary phytic acid (PA; myo-inositol [MI] hexaphosphate) is known to inhibit colon carcinogenesis in rodents. Dietary fiber, which is a negative risk factor of colon cancer, improves characteristics of the colonic environment, such as the content of organic acids and microflora. We hypothesized that dietary PA would improve the colonic luminal environment in rats fed a high-fat diet. To test this hypothesis, rats were fed diets containing 30% beef tallow with 2.04% sodium PA, 0.4% MI, or 1.02% sodium PA + 0.2% MI for 3 weeks. Compared with the control diet, the sodium PA diet up-regulated cecal organic acids, including acetate, propionate, and n-butyrate; this effect was especially prominent for cecal butyrate. The sodium PA + MI diet also significantly increased cecal butyrate, although this effect was less pronounced when compared with the sodium PA diet. The cecal ratio of Lactobacillales, cecal and fecal mucins (an index of intestinal barrier function), and fecal β-glucosidase activity were higher in rats fed the sodium PA diet than in those fed the control diet. The sodium PA, MI, and sodium PA + MI diets decreased levels of serum tumor necrosis factor α, which is a proinflammatory cytokine. Another proinflammatory cytokine, serum interleukin-6, was also down-regulated by the sodium PA and sodium PA + MI diets. These data showed that PA may improve the composition of cecal organic acids, microflora, and mucins, and it may decrease the levels of serum proinflammatory cytokines in rats fed a high-fat, mineral-sufficient diet. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Modulation of cognitive control levels via manipulation of saccade trial-type probability assessed with event-related BOLD fMRI.

    Science.gov (United States)

    Pierce, Jordan E; McDowell, Jennifer E

    2016-02-01

    Cognitive control supports flexible behavior adapted to meet current goals and can be modeled through investigation of saccade tasks with varying cognitive demands. Basic prosaccades (rapid glances toward a newly appearing stimulus) are supported by neural circuitry, including occipital and posterior parietal cortex, frontal and supplementary eye fields, and basal ganglia. These trials can be contrasted with complex antisaccades (glances toward the mirror image location of a stimulus), which are characterized by greater functional magnetic resonance imaging (MRI) blood oxygenation level-dependent (BOLD) signal in the aforementioned regions and recruitment of additional regions such as dorsolateral prefrontal cortex. The current study manipulated the cognitive demands of these saccade tasks by presenting three rapid event-related runs of mixed saccades with a varying probability of antisaccade vs. prosaccade trials (25, 50, or 75%). Behavioral results showed an effect of trial-type probability on reaction time, with slower responses in runs with a high antisaccade probability. Imaging results exhibited an effect of probability in bilateral pre- and postcentral gyrus, bilateral superior temporal gyrus, and medial frontal gyrus. Additionally, the interaction between saccade trial type and probability revealed a strong probability effect for prosaccade trials, showing a linear increase in activation parallel to antisaccade probability in bilateral temporal/occipital, posterior parietal, medial frontal, and lateral prefrontal cortex. In contrast, antisaccade trials showed elevated activation across all runs. Overall, this study demonstrated that improbable performance of a typically simple prosaccade task led to augmented BOLD signal to support changing cognitive control demands, resulting in activation levels similar to the more complex antisaccade task. Copyright © 2016 the American Physiological Society.

  6. Agents that affect cAMP levels or protein kinase A activity modulate memory consolidation when injected into rat hippocampus but not amygdala

    Directory of Open Access Journals (Sweden)

    L. Bevilaqua

    1997-08-01

    Full Text Available Male Wistar rats were trained in one-trial step-down inhibitory avoidance using a 0.4-mA footshock. At various times after training (0, 1.5, 3, 6 and 9 h for the animals implanted into the CA1 region of the hippocampus; 0 and 3 h for those implanted into the amygdala, these animals received microinfusions of SKF38393 (7.5 µg/side, SCH23390 (0.5 µg/side, norepinephrine (0.3 µg/side, timolol (0.3 µg/side, 8-OH-DPAT (2.5 µg/side, NAN-190 (2.5 µg/side, forskolin (0.5 µg/side, KT5720 (0.5 µg/side or 8-Br-cAMP (1.25 µg/side. Rats were tested for retention 24 h after training. When given into the hippocampus 0 h post-training, norepinephrine enhanced memory whereas KT5720 was amnestic. When given 1.5 h after training, all treatments were ineffective. When given 3 or 6 h post-training, 8-Br-cAMP, forskolin, SKF38393, norepinephrine and NAN-190 caused memory facilitation, while KT5720, SCH23390, timolol and 8-OH-DPAT caused retrograde amnesia. Again, at 9 h after training, all treatments were ineffective. When given into the amygdala, norepinephrine caused retrograde facilitation at 0 h after training. The other drugs infused into the amygdala did not cause any significant effect. These data suggest that in the hippocampus, but not in the amygdala, a cAMP/protein kinase A pathway is involved in memory consolidation at 3 and 6 h after training, which is regulated by D1, ß, and 5HT1A receptors. This correlates with data on increased post-training cAMP levels and a dual peak of protein kinase A activity and CREB-P levels (at 0 and 3-6 h in rat hippocampus after training in this task. These results suggest that the hippocampus, but not the amygdala, is involved in long-term storage of step-down inhibitory avoidance in the rat.

  7. Molecular mechanism of the short-term cardiotoxicity caused by 2',3'-dideoxycytidine (ddC): modulation of reactive oxygen species levels and ADP-ribosylation reactions.

    Science.gov (United States)

    Skuta, G; Fischer, G M; Janaky, T; Kele, Z; Szabo, P; Tozser, J; Sumegi, B

    1999-12-15

    The short-term cardiac side effects of 2',3'-dideoxycytidine (ddC, zalcitabine) were studied in rats in order to understand the biochemical events contributing to the development of ddC-induced cardiomyopathy. In developing animals, ddC treatment provoked a surprisingly rapid appearance of cardiac malfunctions characterized by prolonged RR, PR, and QT intervals and J point depression. The energy metabolism in the heart was compromised, characterized by a decreased creatine phosphate/creatine ratio (from 2.05 normal value to 0.75) and a decreased free ATP/ADP ratio (from 332 normal value to 121). The activity of respiratory complexes (NADH: cytochrome c oxidoreductase and cytochrome oxidase) also decreased significantly. Southern blot and polymerase chain reaction analysis did not show deletions or a decrease in the quantity of mitochondrial DNA (mtDNA) deriving from ddC-treated rat hearts, indicating that under our experimental conditions, ddC-induced heart abnormalities were not the direct consequence of mtDNA-related damage. The ddC treatment of rats significantly increased the formation of reactive oxygen species (ROS) in heart and skeletal muscle as determined by the oxidation of non-fluorescent dihydrorhodamine123 to fluorescent rhodamine123 and the oxidation of cellular proteins determined from protein carbonyl content. An activation of the nuclear poly-(ADP-ribose) polymerase (EC 2.4.2.30) and an increase in the mono-ADP-ribosylation of glucose-regulated protein and desmin were observed in the cardiac tissue from ddC-treated animals. A decrease in the quantity of heat shock protein (HSP)70s was also detected, while the level of HSP25 and HSP60 remained unchanged. Surprisingly, ddC treatment induced a skeletal muscle-specific decrease in the quantity of three proteins, one of which was identified by N-terminal sequencing as myoglobin, and another by tandem mass spectrometer sequencing as triosephosphate isomerase (EC 5.3.1.1). These data show that the short

  8. Low-level laser therapy (LLLT) does not reduce subcutaneous adipose tissue by local adipocyte injury but rather by modulation of systemic lipid metabolism.

    Science.gov (United States)

    Jankowski, Marek; Gawrych, Mariusz; Adamska, Urszula; Ciescinski, Jakub; Serafin, Zbigniew; Czajkowski, Rafal

    2017-02-01

    Low-level laser (light) therapy (LLLT) has been applied recently to body contouring. However the mechanism of LLLT-induced reduction of subcutaneous adipose tissue thickness has not been elucidated and proposed hypotheses are highly controversial. Non-obese volunteers were subject to 650nm LLLT therapy. Each patient received 6 treatments 2-3 days apart to one side of the abdomen. The contralateral side was left untreated and served as control. Subjects' abdominal adipose tissue thickness was measured by ultrasound imaging at baseline and 2 weeks post-treatment. Our study is to the best of our knowledge, the largest split-abdomen study employing subcutaneous abdominal fat imaging. We could not show a statistically significant reduction of abdominal subcutaneous adipose tissue by LLLT therapy. Paradoxically when the measurements of the loss of fat thickness on treated side was corrected for change in thickness on non treated side, we have observed that in 8 out of 17 patients LLLT increased adipose tissue thickness. In two patients severe side effect occurred as a result of treatment: one patient developed ulceration within appendectomy scar, the other over the posterior superior iliac spine. The paradoxical net increase in subcutaneous fat thickness observed in some of our patients is a rationale against liquefactive and transitory pore models of LLLT-induced adipose tissue reduction. LLLT devices with laser diode panels applied directly on the skin are not as safe as devices with treatment panels separated from the patient's skin.

  9. Intake of Red Wine in Different Meals Modulates Oxidized LDL Level, Oxidative and Inflammatory Gene Expression in Healthy People: A Randomized Crossover Trial

    Directory of Open Access Journals (Sweden)

    Laura Di Renzo

    2014-01-01

    Full Text Available Several studies have found that adherence to the Mediterranean Diet, including consumption of red wine, is associated with beneficial effects on oxidative and inflammatory conditions. We evaluate the outcome of consumption of a McDonald’s Meal (McD and a Mediterranean Meal (MM, with and without the additive effect of red wine, in order to ascertain whether the addition of the latter has a positive impact on oxidized (ox- LDL and on expression of oxidative and inflammatory genes. A total of 24 subjects were analyzed for ox-LDL, CAT, GPX1, SOD2, SIRT2, and CCL5 gene expression levels, before and after consumption of the 4 different meal combinations with washout intervals between each meal. When red wine is associated with McD or MM, values of ox-LDL are lowered (P<0.05 and expression of antioxidant genes is increased, while CCL5 expression is decreased (P<0.05. SIRT2 expression after MM and fasting with red wine is significantly correlated with downregulation of CCL5 and upregulation of CAT (P<0.001. GPX1 increased significantly in the comparison between baseline and all conditions with red wine. We highlighted for the first time the positive effect of red wine intake combined with different but widely consumed meal types on ox-LDL and gene expression. Trial Registration. This trial is registered with ClinicalTrials.gov NCT01890070.

  10. Intake of Red Wine in Different Meals Modulates Oxidized LDL Level, Oxidative and Inflammatory Gene Expression in Healthy People: A Randomized Crossover Trial

    Science.gov (United States)

    Di Renzo, Laura; Valente, Roberto; Colica, Carmen

    2014-01-01

    Several studies have found that adherence to the Mediterranean Diet, including consumption of red wine, is associated with beneficial effects on oxidative and inflammatory conditions. We evaluate the outcome of consumption of a McDonald's Meal (McD) and a Mediterranean Meal (MM), with and without the additive effect of red wine, in order to ascertain whether the addition of the latter has a positive impact on oxidized (ox-) LDL and on expression of oxidative and inflammatory genes. A total of 24 subjects were analyzed for ox-LDL, CAT, GPX1, SOD2, SIRT2, and CCL5 gene expression levels, before and after consumption of the 4 different meal combinations with washout intervals between each meal. When red wine is associated with McD or MM, values of ox-LDL are lowered (P < 0.05) and expression of antioxidant genes is increased, while CCL5 expression is decreased (P < 0.05). SIRT2 expression after MM and fasting with red wine is significantly correlated with downregulation of CCL5 and upregulation of CAT (P < 0.001). GPX1 increased significantly in the comparison between baseline and all conditions with red wine. We highlighted for the first time the positive effect of red wine intake combined with different but widely consumed meal types on ox-LDL and gene expression. Trial Registration. This trial is registered with ClinicalTrials.gov NCT01890070. PMID:24876915

  11. Atomic level structural modulation during the structural relaxation and its effect on magnetic properties of Fe81Si4B10P4Cu1 nanocrystalline alloy

    Science.gov (United States)

    Cao, C. C.; Zhu, L.; Meng, Y.; Zhai, X. B.; Wang, Y. G.

    2018-06-01

    The evolution of local structure and defects in the Fe81Si4B10P4Cu1 amorphous alloy during the structural relaxation has been investigated by Mössbauer spectroscopy, positron annihilation lifetime spectroscopy and transmission electron microscopy to explore their effects on magnetic properties of the nanocrystalline. The atomic rearrangements at the early stage of the structural relaxation cause the density increase of the amorphous matrix, but the subsequent atomic rearrangements contribute to the transformation of Fe3B-like atomic arrangements to FeB-like ones with the temperature increasing. As the structural relaxation processes, the released Fe atoms both from Fe3B- and Fe3P-like atomic arrangements result in the formation of new Fe clusters and the increase of Fe-Fe coordination number in the existing Fe clusters and the nucleation sites for α-Fe gradually increase, both of which promote the crystallization. However, the homogeneity of amorphous matrix will be finally destroyed under excessive relaxation temperature, which coarsens nanograins during the crystallization instead. Therefore, soft magnetic properties of the Fe81Si4B10P4Cu1 nanocrystalline alloy can be improved by pre-annealing the amorphous precursor at an appropriate temperature due to the atomic level structural optimization.

  12. Automatic modulation classification principles, algorithms and applications

    CERN Document Server

    Zhu, Zhechen

    2014-01-01

    Automatic Modulation Classification (AMC) has been a key technology in many military, security, and civilian telecommunication applications for decades. In military and security applications, modulation often serves as another level of encryption; in modern civilian applications, multiple modulation types can be employed by a signal transmitter to control the data rate and link reliability. This book offers comprehensive documentation of AMC models, algorithms and implementations for successful modulation recognition. It provides an invaluable theoretical and numerical comparison of AMC algo

  13. XPM-induced degradation of multilevel phase modulated channel caused by neighboring NRZ modulated channels

    DEFF Research Database (Denmark)

    Jensen, Jesper Bevensee; Schiellerup, G.; Peucheret, Christophe

    2008-01-01

    The impact of XPM from NRZ modulated channels on an 8-level phase modulated channel in a WDM system was investigated. Requirements on launch power are found. 400 km transmission was achieved with negligible penalty.......The impact of XPM from NRZ modulated channels on an 8-level phase modulated channel in a WDM system was investigated. Requirements on launch power are found. 400 km transmission was achieved with negligible penalty....

  14. Engineering zonal cartilaginous tissue by modulating oxygen levels and mechanical cues through the depth of infrapatellar fat pad stem cell laden hydrogels.

    Science.gov (United States)

    Luo, Lu; O'Reilly, Adam R; Thorpe, Stephen D; Buckley, Conor T; Kelly, Daniel J

    2017-09-01

    Engineering tissues with a structure and spatial composition mimicking those of native articular cartilage (AC) remains a challenge. This study examined if infrapatellar fat pad-derived stem cells (FPSCs) can be used to engineer cartilage grafts with a bulk composition and a spatial distribution of matrix similar to the native tissue. In an attempt to mimic the oxygen gradients and mechanical environment within AC, FPSC-laden hydrogels (either 2 mm or 4 mm in height) were confined to half of their thickness and/or subjected to dynamic compression (DC). Confining FPSC-laden hydrogels was predicted to accentuate the gradient in oxygen tension through the depth of the constructs (higher in the top and lower in the bottom), leading to enhanced glycosaminoglycan (GAG) and collagen synthesis in 2 mm high tissues. When subjected to DC alone, both GAG and collagen accumulation increased within 2 mm high unconfined constructs. Furthermore, the dynamic modulus of constructs increased from 0.96 MPa to 1.45 MPa following the application of DC. There was no synergistic benefit of coupling confinement and DC on overall levels of matrix accumulation; however in all constructs, irrespective of their height, the combination of these boundary conditions led to the development of engineered tissues that spatially best resembled native AC. The superficial region of these constructs mimicked that of native tissue, staining weakly for GAG, strongly for type II collagen, and in 4 mm high tissues more intensely for proteoglycan 4 (lubricin). This study demonstrated that FPSCs respond to joint-like environmental conditions by producing cartilage tissues mimicking native AC. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  15. Recall of threat material is modulated by self or other referencing in people with high or low levels of non-clinical paranoia.

    Science.gov (United States)

    Greer, J; Smailes, D; Spencer, H; Freeston, M; Dudley, R

    2016-03-01

    Biased processing of negatively valenced, and particularly threat-related material plays an important role in the development of paranoid thinking. This has been demonstrated by superior memory for threat-related information in patients with persecutory delusions and in non-clinical paranoia-prone participants. This study examined how emotional material was recalled having been encoded in relation to one self or to another person, in people high or low in paranoid ideation. It was predicted that people high in paranoia would recall more threat related material about others than people low in paranoia owing to being particularly alert to threats from other people. Participants who reported high (N = 30) or low (N = 30) levels of sub-clinical paranoid thinking were presented with a series of threat-related and positive words and were asked to process them in terms of the self, or in terms of a fictional character. As predicted, when words were processed in terms of another person, the high paranoia group recalled more threat-related words than positive words, but when words had been processed in terms of the self, recall of threat-related and positive words did not differ. In contrast, there was no interaction between word-valence and referent in the low paranoia group. These findings are drawn from an analogue sample. Replication in a sample of clinical participants who report persecutory delusions is required. People high in sub-clinical paranoid ideation recalled threat preferentially in relation to other people. Such information processing biases may help understand the development and maintenance of persecutory beliefs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Modulation of O-GlcNAc Levels in the Liver Impacts Acetaminophen-Induced Liver Injury by Affecting Protein Adduct Formation and Glutathione Synthesis.

    Science.gov (United States)

    McGreal, Steven R; Bhushan, Bharat; Walesky, Chad; McGill, Mitchell R; Lebofsky, Margitta; Kandel, Sylvie E; Winefield, Robert D; Jaeschke, Hartmut; Zachara, Natasha E; Zhang, Zhen; Tan, Ee Phie; Slawson, Chad; Apte, Udayan

    2018-04-01

    Overdose of acetaminophen (APAP) results in acute liver failure. We have investigated the role of a posttranslational modification of proteins called O-GlcNAcylation, where the O-GlcNAc transferase (OGT) adds and O-GlcNAcase (OGA) removes a single β-D-N-acetylglucosamine (O-GlcNAc) moiety, in the pathogenesis of APAP-induced liver injury. Hepatocyte-specific OGT knockout mice (OGT KO), which have reduced O-GlcNAcylation, and wild-type (WT) controls were treated with 300 mg/kg APAP and the development of injury was studied over a time course from 0 to 24 h. OGT KO mice developed significantly lower liver injury as compared with WT mice. Hepatic CYP2E1 activity and glutathione (GSH) depletion following APAP treatment were not different between WT and OGT KO mice. However, replenishment of GSH and induction of GSH biosynthesis genes were significantly faster in the OGT KO mice. Next, male C57BL/6 J mice were treated Thiamet-G (TMG), a specific inhibitor of OGA to induce O-GlcNAcylation, 1.5 h after APAP administration and the development of liver injury was studied over a time course of 0-24 h. TMG-treated mice exhibited significantly higher APAP-induced liver injury. Treatment with TMG did not affect hepatic CYP2E1 levels, GSH depletion, APAP-protein adducts, and APAP-induced mitochondrial damage. However, GSH replenishment and GSH biosynthesis genes were lower in TMG-treated mice after APAP overdose. Taken together, these data indicate that induction in cellular O-GlcNAcylation exacerbates APAP-induced liver injury via dysregulation of hepatic GSH replenishment response.

  17. Proposed Lymph Node Staging System Using the International Consensus Guidelines for Lymph Node Levels Is Predictive for Nasopharyngeal Carcinoma Patients From Endemic Areas Treated With Intensity Modulated Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Li, Wen-Fei; Sun, Ying; Mao, Yan-Ping; Chen, Lei; Chen, Yuan-Yuan; Chen, Mo [Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou (China); Liu, Li-Zhi [Imaging Diagnosis and Interventional Center, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou (China); Lin, Ai-Hua [Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou (China); Li, Li [Imaging Diagnosis and Interventional Center, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou (China); Ma, Jun, E-mail: majun2@mail.sysu.edu.cn [Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou (China)

    2013-06-01

    Purpose: To propose a lymph node (N) staging system for nasopharyngeal carcinoma (NPC) based on the International Consensus Guidelines for lymph node (LN) levels and MRI-determined nodal variables. Methods and Materials: The MRI scans and medical records of 749 NPC patients receiving intensity modulated radiation therapy with or without chemotherapy were retrospectively reviewed. The prognostic significance of nodal level, laterality, maximal axial diameter, extracapsular spread, necrosis, and Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) size criteria were analyzed. Results: Nodal level and laterality were the only independent prognostic factors for distant failure and disease failure in multivariate analysis. Compared with unilateral levels Ib, II, III, and/or Va involvement (hazard ratio [HR] 1), retropharyngeal lymph node involvement alone had a similar prognostic value (HR 0.71; 95% confidence interval [CI] 0.43-1.17; P=.17), whereas bilateral levels Ib, II, III, and/or Va involvement (HR 1.65; 95% CI 1.06-2.58; P=.03) and levels IV, Vb, and/or supraclavicular fossa involvement (HR 3.47; 95% CI 1.92-6.29; P<.01) both significantly increased the HR for distant failure. Thus we propose that the N category criteria could be revised as follows: N0, no regional LN metastasis; N1, retropharyngeal lymph node involvement, and/or unilateral levels Ib, II, III, and/or Va involvement; N2, bilateral levels Ib, II, III, and/or Va involvement; N3, levels IV, Vb, and/or supraclavicular fossa involvement. Compared with the 7th edition of the UICC/AJCC criteria, the proposed N staging system provides a more satisfactory distinction between the HRs for regional failure, distant failure, and disease failure in each N category. Conclusions: The proposed N staging system defined by the International Consensus Guidelines and laterality is predictive and practical. However, because of no measurements of the maximal nodal diameter on MRI slices

  18. Evolutionary and developmental modules.

    Science.gov (United States)

    Lacquaniti, Francesco; Ivanenko, Yuri P; d'Avella, Andrea; Zelik, Karl E; Zago, Myrka

    2013-01-01

    The identification of biological modules at the systems level often follows top-down decomposition of a task goal, or bottom-up decomposition of multidimensional data arrays into basic elements or patterns representing shared features. These approaches traditionally have been applied to mature, fully developed systems. Here we review some results from two other perspectives on modularity, namely the developmental and evolutionary perspective. There is growing evidence that modular units of development were highly preserved and recombined during evolution. We first consider a few examples of modules well identifiable from morphology. Next we consider the more difficult issue of identifying functional developmental modules. We dwell especially on modular control of locomotion to argue that the building blocks used to construct different locomotor behaviors are similar across several animal species, presumably related to ancestral neural networks of command. A recurrent theme from comparative studies is that the developmental addition of new premotor modules underlies the postnatal acquisition and refinement of several different motor behaviors in vertebrates.

  19. MEMORY MODULATION

    Science.gov (United States)

    Roozendaal, Benno; McGaugh, James L.

    2011-01-01

    Our memories are not all created equally strong: Some experiences are well remembered while others are remembered poorly, if at all. Research on memory modulation investigates the neurobiological processes and systems that contribute to such differences in the strength of our memories. Extensive evidence from both animal and human research indicates that emotionally significant experiences activate hormonal and brain systems that regulate the consolidation of newly acquired memories. These effects are integrated through noradrenergic activation of the basolateral amygdala which regulates memory consolidation via interactions with many other brain regions involved in consolidating memories of recent experiences. Modulatory systems not only influence neurobiological processes underlying the consolidation of new information, but also affect other mnemonic processes, including memory extinction, memory recall and working memory. In contrast to their enhancing effects on consolidation, adrenal stress hormones impair memory retrieval and working memory. Such effects, as with memory consolidation, require noradrenergic activation of the basolateral amygdala and interactions with other brain regions. PMID:22122145

  20. Mitochondrial DNA levels in Huntington disease leukocytes and dermal fibroblasts.

    Science.gov (United States)

    Jędrak, Paulina; Krygier, Magdalena; Tońska, Katarzyna; Drozd, Małgorzata; Kaliszewska, Magdalena; Bartnik, Ewa; Sołtan, Witold; Sitek, Emilia J; Stanisławska-Sachadyn, Anna; Limon, Janusz; Sławek, Jarosław; Węgrzyn, Grzegorz; Barańska, Sylwia

    2017-08-01

    Huntington disease (HD) is an inherited neurodegenerative disorder caused by mutations in the huntingtin gene. Involvement of mitochondrial dysfunctions in, and especially influence of the level of mitochondrial DNA (mtDNA) on, development of this disease is unclear. Here, samples of blood from 84 HD patients and 79 controls, and dermal fibroblasts from 10 HD patients and 9 controls were analysed for mtDNA levels. Although the type of mitochondrial haplogroup had no influence on the mtDNA level, and there was no correlation between mtDNA level in leukocytes in HD patients and various parameters of HD severity, some considerable differences between HD patients and controls were identified. The average mtDNA/nDNA relative copy number was significantly higher in leukocytes, but lower in fibroblasts, of symptomatic HD patients relative to the control group. Moreover, HD women displayed higher mtDNA levels in leukocytes than HD men. Because this is the largest population analysed to date, these results might contribute to explanation of discrepancies between previously published studies concerning levels of mtDNA in cells of HD patients. We suggest that the size of the investigated population and type of cells from which DNA is isolated could significantly affect results of mtDNA copy number estimation in HD. Hence, these parameters should be taken into consideration in studies on mtDNA in HD, and perhaps also in other diseases where mitochondrial dysfunction occurs.

  1. Rate modulation detection thresholds for cochlear implant users.

    Science.gov (United States)

    Brochier, Tim; McKay, Colette; McDermott, Hugh

    2018-02-01

    The perception of temporal amplitude modulations is critical for speech understanding by cochlear implant (CI) users. The present study compared the ability of CI users to detect sinusoidal modulations of the electrical stimulation rate and current level, at different presentation levels (80% and 40% of the dynamic range) and modulation frequencies (10 and 100 Hz). Rate modulation detection thresholds (RMDTs) and amplitude modulation detection thresholds (AMDTs) were measured and compared to assess whether there was a perceptual advantage to either modulation method. Both RMDTs and AMDTs improved with increasing presentation level and decreasing modulation frequency. RMDTs and AMDTs were correlated, indicating that a common processing mechanism may underlie the perception of rate modulation and amplitude modulation, or that some subject-dependent factors affect both types of modulation detection.

  2. Medical Terminology: Root Words. Health Occupations Education Module.

    Science.gov (United States)

    Temple Univ., Philadelphia, PA. Div. of Vocational Education.

    This module on medical terminology (root words) is one of 17 modules designed for individualized instruction in health occupations education programs at both the secondary and postsecondary levels. This module consists of an introduction to root words, a list of resources needed, procedures for using the module, a list of terminology used in the…

  3. Health Occupations Module. The Skeletal System--II.

    Science.gov (United States)

    Temple Univ., Philadelphia, PA. Div. of Vocational Education.

    This module on the skeletal system is one of eight modules designed for individualized instruction in health occupations education programs at both the secondary and postsecondary levels. This module contains an introduction to the module topic, two objectives (e.g., list the types of joints and movements, and give examples), and two learning…

  4. Health Occupations Module. The Skeletal System--I.

    Science.gov (United States)

    Temple Univ., Philadelphia, PA. Div. of Vocational Education.

    This module on the skeletal system is one of eight modules designed for individualized instruction in health occupations education programs at both the secondary and postsecondary levels. This module contains an introduction to the module topic, three objectives (e.g., define the skeletal system and list its functions), and three learning…

  5. Fast Convolution Module (Fast Convolution Module)

    National Research Council Canada - National Science Library

    Bierens, L

    1997-01-01

    This report describes the design and realisation of a real-time range azimuth compression module, the so-called 'Fast Convolution Module', based on the fast convolution algorithm developed at TNO-FEL...

  6. Repeated administration of alpha7 nicotinic acetylcholine receptor (nAChR) agonists, but not positive allosteric modulators, increases alpha7 nAChR levels in the brain

    DEFF Research Database (Denmark)

    Christensen, Ditte Z; Mikkelsen, Jens D; Hansen, Henrik H

    2010-01-01

    AChR binding sites in several brain regions, particularly in the prefrontal cortex. The alpha7 nAChR agonists SSR180711 and PNU-282987 also increase [(125)I]-BTX binding, suggesting that this is a general consequence of alpha7 nAChR agonism. Interestingly, the alpha7 nAChR positive allosteric modulators PNU......The alpha7 nicotinic acetylcholine receptor (nAChR) is an important target for treatment of cognitive deficits in schizophrenia and Alzheimer's disease. However, the receptor desensitizes rapidly in vitro, which has led to concern regarding its applicability as a clinically relevant drug target....... Here we investigate the effects of repeated agonism on alpha7 nAChR receptor levels and responsiveness in vivo in rats. Using [(125)I]-alpha-bungarotoxin (BTX) autoradiography we show that acute or repeated administration with the selective alpha7 nAChR agonist A-582941 increases the number of alpha7 n...

  7. Module theory, extending modules and generalizations

    CERN Document Server

    Tercan, Adnan

    2016-01-01

    The main focus of this monograph is to offer a comprehensive presentation of known and new results on various generalizations of CS-modules and CS-rings. Extending (or CS) modules are generalizations of injective (and also semisimple or uniform) modules. While the theory of CS-modules is well documented in monographs and textbooks, results on generalized forms of the CS property as well as dual notions are far less present in the literature. With their work the authors provide a solid background to module theory, accessible to anyone familiar with basic abstract algebra. The focus of the book is on direct sums of CS-modules and classes of modules related to CS-modules, such as relative (injective) ejective modules, (quasi) continuous modules, and lifting modules. In particular, matrix CS-rings are studied and clear proofs of fundamental decomposition results on CS-modules over commutative domains are given, thus complementing existing monographs in this area. Open problems round out the work and establish the...

  8. Hepatic uptake of conjugated bile acids is mediated by both sodium taurocholate cotransporting polypeptide and organic anion transporting polypeptides and modulated by intestinal sensing of plasma bile acid levels in mice.

    Science.gov (United States)

    Slijepcevic, Davor; Roscam Abbing, Reinout L P; Katafuchi, Takeshi; Blank, Antje; Donkers, Joanne M; van Hoppe, Stéphanie; de Waart, Dirk R; Tolenaars, Dagmar; van der Meer, Jonathan H M; Wildenberg, Manon; Beuers, Ulrich; Oude Elferink, Ronald P J; Schinkel, Alfred H; van de Graaf, Stan F J

    2017-11-01

    The Na + -taurocholate cotransporting polypeptide (NTCP/SLC10A1) is believed to be pivotal for hepatic uptake of conjugated bile acids. However, plasma bile acid levels are normal in a subset of NTCP knockout mice and in mice treated with myrcludex B, a specific NTCP inhibitor. Here, we elucidated which transport proteins mediate the hepatic uptake of conjugated bile acids and demonstrated intestinal sensing of elevated bile acid levels in plasma in mice. Mice or healthy volunteers were treated with myrcludex B. Hepatic bile acid uptake kinetics were determined in wild-type (WT), organic anion transporting polypeptide (OATP) knockout mice (lacking Slco1a/1b isoforms), and human OATP1B1-transgenic mice. Effects of fibroblast growth factor 19 (FGF19) on hepatic transporter mRNA levels were assessed in rat hepatoma cells and in mice by peptide injection or adeno-associated virus-mediated overexpression. NTCP inhibition using myrcludex B had only moderate effects on bile acid kinetics in WT mice, but completely inhibited active transport of conjugated bile acid species in OATP knockout mice. Cholesterol 7α-hydroxylase Cyp7a1 expression was strongly down-regulated upon prolonged inhibition of hepatic uptake of conjugated bile acids. Fgf15 (mouse counterpart of FGF19) expression was induced in hypercholanemic OATP and NTCP knockout mice, as well as in myrcludex B-treated cholestatic mice, whereas plasma FGF19 was not induced in humans treated with myrcludex B. Fgf15/FGF19 expression was induced in polarized human enterocyte-models and mouse organoids by basolateral incubation with a high concentration (1 mM) of conjugated bile acids. NTCP and OATPs contribute to hepatic uptake of conjugated bile acids in mice, whereas the predominant uptake in humans is NTCP mediated. Enterocytes sense highly elevated levels of (conjugated) bile acids in the systemic circulation to induce FGF15/19, which modulates hepatic bile acid synthesis and uptake. (Hepatology 2017;66:1631-1643).

  9. Reduced multiplication modules

    Indian Academy of Sciences (India)

    if M is a von Neumann regular module (VNM); i.e., every principal submodule of M is a summand submodule. Also if M is an injective R-module, then M is a VNM. Keywords. Multiplication module; reduced module; minimal prime submodule;. Zariski topology; extremally disconnected. 1. Introduction. In this paper all rings are ...

  10. Modulational effects in accelerators

    International Nuclear Information System (INIS)

    Satogata, T.

    1997-01-01

    We discuss effects of field modulations in accelerators, specifically those that can be used for operational beam diagnostics and beam halo control. In transverse beam dynamics, combined effects of nonlinear resonances and tune modulations influence diffusion rates with applied tune modulation has been demonstrated. In the longitudinal domain, applied RF phase and voltage modulations provide mechanisms for parasitic halo transport, useful in slow crystal extraction. Experimental experiences with transverse tune and RF modulations are also discussed

  11. School based assessment module for invasion games category in ...

    African Journals Online (AJOL)

    School based assessment module for invasion games category in physical education. ... This study identify the level of basic skills of invasion games category when using School Based Assessment Module. ... AJOL African Journals Online.

  12. WRAP module 1 treatment plan

    International Nuclear Information System (INIS)

    Mayancsik, B.A.

    1995-05-01

    This document provides the methodology to treat waste in the Waste Receiving and Processing Module 1 facility to meet the Resource Conservation and Recovery Act (RCRA) land disposal restrictions or the Waste Isolation and Pilot Plant waste acceptance criteria. This includes Low-Level Mixed Waste, Transuranic Waste, and Transuranic Mixed Waste

  13. Modulation of gene expression made easy

    DEFF Research Database (Denmark)

    Solem, Christian; Jensen, Peter Ruhdal

    2002-01-01

    A new approach for modulating gene expression, based on randomization of promoter (spacer) sequences, was developed. The method was applied to chromosomal genes in Lactococcus lactis and shown to generate libraries of clones with broad ranges of expression levels of target genes. In one example...... that the method can be applied to modulating the expression of native genes on the chromosome. We constructed a series of strains in which the expression of the las operon, containing the genes pfk, pyk, and ldh, was modulated by integrating a truncated copy of the pfk gene. Importantly, the modulation affected...

  14. WRAP Module 1 sampling and analysis plan

    International Nuclear Information System (INIS)

    Mayancsik, B.A.

    1995-01-01

    This document provides the methodology to sample, screen, and analyze waste generated, processed, or otherwise the responsibility of the Waste Receiving and Processing Module 1 facility. This includes Low-Level Waste, Transuranic Waste, Mixed Waste, and Dangerous Waste

  15. WRAP Module 1 sampling and analysis plan

    Energy Technology Data Exchange (ETDEWEB)

    Mayancsik, B.A.

    1995-03-24

    This document provides the methodology to sample, screen, and analyze waste generated, processed, or otherwise the responsibility of the Waste Receiving and Processing Module 1 facility. This includes Low-Level Waste, Transuranic Waste, Mixed Waste, and Dangerous Waste.

  16. 16 de Septiembre, 1810 Module. Secondary Level. [16 of September, 1810 Module. Secondary Level.

    Science.gov (United States)

    Crystal City Independent School District, TX.

    Independence for Mexico took 11 years to achieve. Before its independence Mexico was ruled by Spain and had a basic caste system of indios, mestizos, criollos, and gachupines. The gachupines and criollos ruled the government and exploited the indios and mestizos. When the criollos became dissatisfied with being secondary to the gachupines, they…

  17. Electroabsorption optical modulator

    Energy Technology Data Exchange (ETDEWEB)

    Skogen, Erik J.

    2017-11-21

    An electroabsorption modulator incorporates waveguiding regions along the length of the modulator that include quantum wells where at least two of the regions have quantum wells with different bandgaps. In one embodiment of the invention, the regions are arranged such that the quantum wells have bandgaps with decreasing bandgap energy along the length of the modulator from the modulator's input to its output. The bandgap energy of the quantum wells may be decreased in discrete steps or continuously. Advantageously, such an arrangement better distributes the optical absorption as well as the carrier density along the length of the modulator. Further advantageously, the modulator may handle increased optical power as compared with prior art modulators of similar dimensions, which allows for improved link gain when the optical modulator is used in an analog optical communication link.

  18. CDC 7600 module slice

    CERN Multimedia

    Each module contained 8 circuit cards for a total of about 300-500 uncovered transistors packaged with face plates so the Freon plates wouldn't touch the circuits. (cooling plates that surrounded each module).

  19. Exploration Augmentation Module Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The Exploration Augmentation Module (EAM) project goal is to design and deliver a flight module that is to be deployed to Earth-Lunar Distant Retrograde Orbit (DRO)....

  20. CDC 6600 Cordwood Module

    CERN Multimedia

    1964-01-01

    The CDC 6600 cordwood module containing 64 silicon transistors. The module was mounted between two plates that were cooled conductive by a refrigeration unit via the front panel. The construction of this module uses the cord method, so called because the resistors seem to be stacked like cord between the two circuit boards in order to obtain a high density. The 6600 model contained nearly 6,000 such modules.

  1. Modulating lignin in plants

    Science.gov (United States)

    Apuya, Nestor; Bobzin, Steven Craig; Okamuro, Jack; Zhang, Ke

    2013-01-29

    Materials and methods for modulating (e.g., increasing or decreasing) lignin content in plants are disclosed. For example, nucleic acids encoding lignin-modulating polypeptides are disclosed as well as methods for using such nucleic acids to generate transgenic plants having a modulated lignin content.

  2. An investigation into modulators

    International Nuclear Information System (INIS)

    Heine, E.

    1988-01-01

    In the framework of the MEA-update it is important to establish which modulators are necessary. In this report it is lookedif the existing modulators can be maintained or new modulators have to be made. Besides technical aspects also material expenses and necessary manpower play a role. 12 figs.; 6 tabs

  3. Weakly Coretractable Modules

    Science.gov (United States)

    Hadi, Inaam M. A.; Al-aeashi, Shukur N.

    2018-05-01

    If R is a ring with identity and M is a unitary right R-module. Here we introduce the class of weakly coretractable module. Some basic properties are investigated and some relationships between these modules and other related one are introduced.

  4. Amplitude modulation detection with concurrent frequency modulation.

    Science.gov (United States)

    Nagaraj, Naveen K

    2016-09-01

    Human speech consists of concomitant temporal modulations in amplitude and frequency that are crucial for speech perception. In this study, amplitude modulation (AM) detection thresholds were measured for 550 and 5000 Hz carriers with and without concurrent frequency modulation (FM), at AM rates crucial for speech perception. Results indicate that adding 40 Hz FM interferes with AM detection, more so for 5000 Hz carrier and for frequency deviations exceeding the critical bandwidth of the carrier frequency. These findings suggest that future cochlear implant processors, encoding speech fine-structures may consider limiting the FM to narrow bandwidth and to low frequencies.

  5. Attention modulates visual size adaptation.

    Science.gov (United States)

    Kreutzer, Sylvia; Fink, Gereon R; Weidner, Ralph

    2015-01-01

    The current study determined in healthy subjects (n = 16) whether size adaptation occurs at early, i.e., preattentive, levels of processing or whether higher cognitive processes such as attention can modulate the illusion. To investigate this issue, bottom-up stimulation was kept constant across conditions by using a single adaptation display containing both small and large adapter stimuli. Subjects' attention was directed to either the large or small adapter stimulus by means of a luminance detection task. When attention was directed toward the small as compared to the large adapter, the perceived size of the subsequent target was significantly increased. Data suggest that different size adaptation effects can be induced by one and the same stimulus depending on the current allocation of attention. This indicates that size adaptation is subject to attentional modulation. These findings are in line with previous research showing that transient as well as sustained attention modulates visual features, such as contrast sensitivity and spatial frequency, and influences adaptation in other contexts, such as motion adaptation (Alais & Blake, 1999; Lankheet & Verstraten, 1995). Based on a recently suggested model (Pooresmaeili, Arrighi, Biagi, & Morrone, 2013), according to which perceptual adaptation is based on local excitation and inhibition in V1, we conclude that guiding attention can boost these local processes in one or the other direction by increasing the weight of the attended adapter. In sum, perceptual adaptation, although reflected in changes of neural activity at early levels (as shown in the aforementioned study), is nevertheless subject to higher-order modulation.

  6. Divisible ℤ-modules

    Directory of Open Access Journals (Sweden)

    Futa Yuichi

    2016-03-01

    Full Text Available In this article, we formalize the definition of divisible ℤ-module and its properties in the Mizar system [3]. We formally prove that any non-trivial divisible ℤ-modules are not finitely-generated.We introduce a divisible ℤ-module, equivalent to a vector space of a torsion-free ℤ-module with a coefficient ring ℚ. ℤ-modules are important for lattice problems, LLL (Lenstra, Lenstra and Lovász base reduction algorithm [15], cryptographic systems with lattices [16] and coding theory [8].

  7. Module-Integrated Power Converters Based on Universal Dock

    Energy Technology Data Exchange (ETDEWEB)

    Chapman, Patrick; Rodriguez, Fernando

    2015-03-13

    Solar power installations using alternating current photovoltaic (ACPV) modules have significant cost and performance advantages over systems using conventional solar modules and string inverters. ACPV modules have improved energy harvest due to module-level power point tracking and redundancy. More importantly, ACPV modules are easier and cheaper to install, lowering the total installed cost, indirect costs, and barriers to market entry. Furthermore, ACPV modules have communications and data logging capability, yielding module-level telemetry data that is useful in site diagnostics and other data applications. The products of these efforts were threefold. First, an advanced microinverter power topology was developed, modeled, simulated, and tested. Second, new microinverter enclosure concepts were developed and tested. Third, a new ACPV module prototype was constructed, combining the power topology and the enclosure concepts. SolarBridge filed for patents in each of these areas and is transitioning the project from a concept phase to full development.

  8. Current level detector

    International Nuclear Information System (INIS)

    Kerns, C.R.

    1977-01-01

    A device is provided for detecting the current level of a dc signal. It includes an even harmonic modulator to which a reference ac signal is applied. The unknown dc signal acts on the reference ac signal so that the output of the modulator includes an even harmonic whose amplitude is proportional to the unknown dc current. The device may be used to provide overcurrent protection for proportional wire chambers

  9. Direct RF modulation transmitter, sampling clock frequency setting method for direct RF modulation transmitter

    NARCIS (Netherlands)

    Fukuda, Shuichi; Nauta, Bram

    2013-01-01

    PROBLEM TO BE SOLVED: To provide a direct RF modulation transmitter capable of satisfying a radiation level regulation even without providing a SAW filter. SOLUTION: A direct RF modulation transmitter includes: digital/RF converters 105, 106 to which an I digital baseband signal, a Q digital

  10. Direct RF modulation transmitter, sampling clock frequency setting method for direct RF modulation transmitter

    NARCIS (Netherlands)

    Fukuda, Shuichi; Nauta, Bram

    2014-01-01

    PROBLEM TO BE SOLVED: To provide a direct RF modulation transmitter capable of satisfying a radiation level regulation even without providing a SAW filter. SOLUTION: A direct RF modulation transmitter includes: digital/RF converters 105, 106 to which an I digital baseband signal, a Q digital

  11. Classes of modules

    CERN Document Server

    Dauns, John

    2006-01-01

    Because traditional ring theory places restrictive hypotheses on all submodules of a module, its results apply only to small classes of already well understood examples. Often, modules with infinite Goldie dimension have finite-type dimension, making them amenable to use with type dimension, but not Goldie dimension. By working with natural classes and type submodules (TS), Classes of Modules develops the foundations and tools for the next generation of ring and module theory. It shows how to achieve positive results by placing restrictive hypotheses on a small subset of the complement submodules, Furthermore, it explains the existence of various direct sum decompositions merely as special cases of type direct sum decompositions. Carefully developing the foundations of the subject, the authors begin by providing background on the terminology and introducing the different module classes. The modules classes consist of torsion, torsion-free, s[M], natural, and prenatural. They expand the discussion by exploring...

  12. FASTBUS Snoop Diagnostic Module

    International Nuclear Information System (INIS)

    Walz, H.V.; Downing, R.

    1980-11-01

    Development of the FASTBUS Snoop Module, undertaken as part of the prototype program for the new interlaboratory data bus standard, is described. The Snoop Module resides on a FASTBUS crate segment and provides diagnostic monitoring and testing capability. Communication with a remote host computer is handled independent of FASTBUS through a serial link. The module consists of a high-speed ECL front-end to monitor and single-step FASTBUS cycles, a master-slave interface, and a control microprocessor with serial communication ports. Design details and performance specifications of the prototype module are reported. 9 figures, 1 table

  13. Bracket for photovoltaic modules

    Science.gov (United States)

    Ciasulli, John; Jones, Jason

    2014-06-24

    Brackets for photovoltaic ("PV") modules are described. In one embodiment, a saddle bracket has a mounting surface to support one or more PV modules over a tube, a gusset coupled to the mounting surface, and a mounting feature coupled to the gusset to couple to the tube. The gusset can have a first leg and a second leg extending at an angle relative to the mounting surface. Saddle brackets can be coupled to a torque tube at predetermined locations. PV modules can be coupled to the saddle brackets. The mounting feature can be coupled to the first gusset and configured to stand the one or more PV modules off the tube.

  14. Crossed modules of racks

    OpenAIRE

    Crans, Alissa S.; Wagemann, Friedrich

    2014-01-01

    We generalize the notion of a crossed module of groups to that of a crossed module of racks. We investigate the relation to categorified racks, namely strict 2-racks, and trunk-like objects in the category of racks, generalizing the relation between crossed modules of groups and strict 2-groups. Then we explore topological applications. We show that by applying the rack-space functor, a crossed module of racks gives rise to a covering. Our main result shows how the fundamental racks associate...

  15. Model theory and modules

    CERN Document Server

    Prest, M

    1988-01-01

    In recent years the interplay between model theory and other branches of mathematics has led to many deep and intriguing results. In this, the first book on the topic, the theme is the interplay between model theory and the theory of modules. The book is intended to be a self-contained introduction to the subject and introduces the requisite model theory and module theory as it is needed. Dr Prest develops the basic ideas concerning what can be said about modules using the information which may be expressed in a first-order language. Later chapters discuss stability-theoretic aspects of module

  16. Delphi Accounts Receivable Module -

    Data.gov (United States)

    Department of Transportation — Delphi accounts receivable module contains the following data elements, but are not limited to customer information, cash receipts, line of accounting details, bill...

  17. Trainer module for security control center operations

    International Nuclear Information System (INIS)

    Bernard, E.A.

    1982-01-01

    An operator trainer module has been developed to be used with the security control center equipment to be installed as part of a safeguards physical protection system. The module is designed to provide improved training and testing capabilities for control center operators through the use of simulations for perimeter equipment operations. Operators, through the trainer module, can be challenged with a variety of realistic situations which require responsive action identical to that needed in an actual system. This permits a consistent evaluation and confirmation of operator capabilities prior to assignment as an operator and allows for periodic retesting to verify that adequate performance levels are maintained

  18. Peltier coefficient measurement in a thermoelectric module

    International Nuclear Information System (INIS)

    Garrido, Javier; Casanovas, Alejandro; Chimeno, José María

    2013-01-01

    A new method for measuring the Peltier coefficient in a thermocouple X/Y based on the energy balance at the junction has been proposed recently. This technique needs only the hot and cold temperatures of a thermoelectric module when an electric current flows through it as the operational variables. The temperature evolutions of the two module sides provide an evident and accurate idea of the Peltier effect. From these temperatures, the heat transfer between the module and the ambient is also evaluated. The thermoelectric phenomena are described in the framework of an observable theory. Based on this procedure, an experiment is presented for a university teaching laboratory at the undergraduate level. (paper)

  19. Design and Modeling a New Optical Modulator

    Directory of Open Access Journals (Sweden)

    Mohammad MEZAAEL

    2009-06-01

    Full Text Available A new opt modulator device using a Silicon Schottky Photodiode Device (s.s.p.d is proposed. The s.s.p.d. is fabricated in laboratory and has been used to mix an intensity modulated laser beam with a high frequency. The effects of modulating the high frequency signal before mixing on the photovoltage enhancement of the s.s.p.d is studied. A significant reduction in the required drive level of the high frequency input signal was achieved. Such a mixer could be use in radar and other communication systems.

  20. ES 1010 software for testing CAMAC modules

    International Nuclear Information System (INIS)

    Ableev, V.G.; Basiladze, S.G.; Zaporozhets, S.A.; Piskunov, N.M.; Ryabtsov, V.D.; Sitnik, I.M.; Strokovskij, E.A.; Sharov, V.I.

    1977-01-01

    Test programs for digital and analog-digital CAMAC modules applied in physical experiments are described. Algorithms were written in FORTRAN-4 language for testing, data acquisition, processing and data control. ASSEMBLER ES 1010 subroutines were used for data acquisition and CAMAC module control. This allowed one to take advantages of a high level language for data processing and display, as well as for achieving an interface with the CAMAC hardware. Software applied enables one to improve considerably adjustment of CAMAC modules and to obtain their operational characteristics

  1. Effects of amplitude modulation on perception of wind turbine noise

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Ki Seop; Lee, Soo Gab; Gwak, Doo Young [Dept. of Mechanical and Aerospace Engineering, Seoul National University, Seoul (Korea, Republic of); Seong, Yeol Wan [Ammunition Engineering Team, Defense Agency for Technology and Quality, Daejeon (Korea, Republic of); Lee, Seung Hoon [Aerodynamics Research Team, Korea Aerospace Research Institute, Daejeon (Korea, Republic of); Hong, Ji Young [Transportation Environmental Research Team, Green Transport and Logistics Institute, Korea Railroad Research Institute, Uiwang (Korea, Republic of)

    2016-10-15

    Wind turbine noise is considered to be easily detectable and highly annoying at relatively lower sound levels than other noise sources. Many previous studies attributed this characteristic to amplitude modulation. However, it is unclear whether amplitude modulation is the main cause of these properties of wind turbine noise. Therefore, the aim of the current study is to identify the relationship between amplitude modulation and these two properties of wind turbine noise. For this investigation, two experiments were conducted. In the first experiment, 12 participants determined the detection thresholds of six target sounds in the presence of background noise. In the second experiment, 12 participants matched the loudness of modified sounds without amplitude modulation to that of target sounds with amplitude modulation. The results showed that the detection threshold was lowered as the modulation depth increased; additionally, sounds with amplitude modulation had higher subjective loudness than those without amplitude modulation.

  2. Tuning of Human Modulation Filters Is Carrier-Frequency Dependent

    Science.gov (United States)

    Simpson, Andrew J. R.; Reiss, Joshua D.; McAlpine, David

    2013-01-01

    Recent studies employing speech stimuli to investigate ‘cocktail-party’ listening have focused on entrainment of cortical activity to modulations at syllabic (5 Hz) and phonemic (20 Hz) rates. The data suggest that cortical modulation filters (CMFs) are dependent on the sound-frequency channel in which modulations are conveyed, potentially underpinning a strategy for separating speech from background noise. Here, we characterize modulation filters in human listeners using a novel behavioral method. Within an ‘inverted’ adaptive forced-choice increment detection task, listening level was varied whilst contrast was held constant for ramped increments with effective modulation rates between 0.5 and 33 Hz. Our data suggest that modulation filters are tonotopically organized (i.e., vary along the primary, frequency-organized, dimension). This suggests that the human auditory system is optimized to track rapid (phonemic) modulations at high sound-frequencies and slow (prosodic/syllabic) modulations at low frequencies. PMID:24009759

  3. Effects of amplitude modulation on perception of wind turbine noise

    International Nuclear Information System (INIS)

    Yoon, Ki Seop; Lee, Soo Gab; Gwak, Doo Young; Seong, Yeol Wan; Lee, Seung Hoon; Hong, Ji Young

    2016-01-01

    Wind turbine noise is considered to be easily detectable and highly annoying at relatively lower sound levels than other noise sources. Many previous studies attributed this characteristic to amplitude modulation. However, it is unclear whether amplitude modulation is the main cause of these properties of wind turbine noise. Therefore, the aim of the current study is to identify the relationship between amplitude modulation and these two properties of wind turbine noise. For this investigation, two experiments were conducted. In the first experiment, 12 participants determined the detection thresholds of six target sounds in the presence of background noise. In the second experiment, 12 participants matched the loudness of modified sounds without amplitude modulation to that of target sounds with amplitude modulation. The results showed that the detection threshold was lowered as the modulation depth increased; additionally, sounds with amplitude modulation had higher subjective loudness than those without amplitude modulation

  4. Growth Modulation in Achondroplasia.

    Science.gov (United States)

    McClure, Philip K; Kilinc, Eray; Birch, John G

    2017-09-01

    Achondroplasia is the most common skeletal dysplasia with a rate of nearly 1/10,000. The development of lower extremity deformity is well documented, and various modes of correction have been reported. There are no reports on the use of growth modulation to correct angular deformity in achondroplasia. Medical Records from 1985 to 2015 were reviewed for the diagnosis of achondroplasia and growth modulation procedures. Patients who had been treated for angular deformity of the legs by growth modulation were identified. A detailed analysis of their medical record and preoperative and final lower extremity radiographs was completed. Four patients underwent growth modulation procedures, all to correct existing varus deformity of the legs. Three of the 4 patients underwent bilateral distal femoral and proximal tibial growth modulation. The remaining patient underwent tibial correction only. Two of the 4 patients had a combined proximal fibular epiphysiodesis. All limbs had some improvement of alignment; however, 1 patient went on to bilateral osteotomies. Only 1 limb corrected to a neutral axis with growth modulation alone at last follow-up, initial implantation was done before 5 years of age. Growth modulation is an effective means for deformity correction in the setting of achondroplasia. However implantation may need to be done earlier than would be typical for patients without achondroplasia. Osteotomy may still be required after growth modulation for incomplete correction.

  5. Defect detection module

    International Nuclear Information System (INIS)

    Ernwein, R.; Westermann, G.

    1986-01-01

    The ''defect detector'' module is aimed at exceptional event or state recording. Foreseen for voltage presence monitoring on high supply voltage module of drift chambers, its characteristics can also show up the vanishing of supply voltage and take in account transitory fast signals [fr

  6. The Strip Module

    DEFF Research Database (Denmark)

    Pedersen, Tommy

    1996-01-01

    When the behaviour of a ship in waves is to be predicted it is convenient to have a tool which includes different approaches to the problem.The aim of this project is to develop such a tool named the strip theory module. The strip theory module will consist of submodules dependent on the I...

  7. The FPAX fastbus module

    International Nuclear Information System (INIS)

    Barlag, S.; Bouquet, B.; Lavigne, B.; Rypko, J.

    1989-07-01

    The FPAX is a Fastbus module with 4 independent, 2 slave and 2 master, ports on two segments. It operates as a normal master on either segment or as a Block-Mover on both. The processor board is based on a 68020 microprocessor. A local/network switch allows operation as a host or as a normal module on the Fastbus network

  8. OCGen Module Mooring Project

    Energy Technology Data Exchange (ETDEWEB)

    McEntee, Jarlath [Ocean Renewable Power Company, LLC, Portland, ME (United States)

    2015-02-06

    Ocean Renewable Power Company's OCGen Module Mooring Project provided an extensive research, design, development, testing and data collection effort and analysis conducted with respect to a positively buoyant, submerged MHK device secured to the seabed using a tensioned mooring system. Different analytic tools were evaluated for their utility in the design of submerged systems and their moorings. Deployment and testing of a prototype OCGen® system provided significant data related to mooring line loads and system attitude and station keeping. Mooring line loads were measured in situ and reported against flow speeds. The Project made a significant step in the development of designs, methodologies and practices related to floating and mooring of marine hydrokinetic (MHK) devices. Importantly for Ocean Renewable Power Company, the Project provided a sound basis for advancing a technically and commercially viable OCGen® Power System. The OCGen® Power System is unique in the MHK industry and, in itself, offers distinct advantages of MHK devices that are secured to the seabed using fixed structural frames. Foremost among these advantages are capital and operating cost reductions and increased power extraction by allowing the device to be placed at the most energetic level of the water column.

  9. Photovoltaic module and laminate

    Science.gov (United States)

    Bunea, Gabriela E.; Kim, Sung Dug; Kavulak, David F.J.

    2018-04-10

    A photovoltaic module is disclosed. The photovoltaic module has a first side directed toward the sun during normal operation and a second, lower side. The photovoltaic module comprises a perimeter frame and a photovoltaic laminate at least partially enclosed by and supported by the perimeter frame. The photovoltaic laminate comprises a transparent cover layer positioned toward the first side of the photovoltaic module, an upper encapsulant layer beneath and adhering to the cover layer, a plurality of photovoltaic solar cells beneath the upper encapsulant layer, the photovoltaic solar cells electrically interconnected, a lower encapsulant layer beneath the plurality of photovoltaic solar cells, the upper and lower encapsulant layers enclosing the plurality of photovoltaic solar cells, and a homogenous rear environmental protection layer, the rear environmental protection layer adhering to the lower encapsulant layer, the rear environmental protection layer exposed to the ambient environment on the second side of the photovoltaic module.

  10. Solar energy modulator

    Science.gov (United States)

    Hale, R. R. (Inventor); Mcdougal, A. R.

    1984-01-01

    A module is described with a receiver having a solar energy acceptance opening and supported by a mounting ring along the optic axis of a parabolic mirror in coaxial alignment for receiving solar energy from the mirror, and a solar flux modulator plate for varying the quantity of solar energy flux received by the acceptance opening of the module. The modulator plate is characterized by an annular, plate-like body, the internal diameter of which is equal to or slightly greater than the diameter of the solar energy acceptance opening of the receiver. Slave cylinders are connected to the modulator plate for supporting the plate for axial displacement along the axis of the mirror, therby shading the opening with respect to solar energy flux reflected from the surface of the mirror to the solar energy acceptance opening.

  11. Medical Terminology: Latin Words/Abbreviations; Special Signs and Symbols. Health Occupations Education Module.

    Science.gov (United States)

    Temple Univ., Philadelphia, PA. Div. of Vocational Education.

    This module on medical terminology (using Latin words/abbreviations; special signs and symbols) is one of 17 modules designed for individualized instruction in health occupations education programs at both the secondary and postsecondary levels. This module consists of an introduction to the module topic, a list of resources needed, and three…

  12. Medical Terminology: Using Some Common Prefixes, Suffixes, and Roots. Health Occupations Education Module.

    Science.gov (United States)

    Temple Univ., Philadelphia, PA. Div. of Vocational Education.

    This module on medical terminology (using common prefixes, suffixes, and root words) is one of 17 modules designed for individualized instruction in health occupations education programs at both the secondary and postsecondary levels. This module consists of an introduction to the module topic, a list of resources needed, and three learning…

  13. Introducing GIS across Levels: Designing for Diversity

    Science.gov (United States)

    Barros, Joana

    2017-01-01

    The paper proposes a strategy for designing introductory GIS modules at Birkbeck, University of London. Seven design aspects or elements (content, practical exercises, assessment, pace, mode, level of support, and level of difficulty) for tailoring modules at appropriate levels and for diversity are introduced and their application in Birkbeck's…

  14. Individualized volume CT dose index determined by cross-sectional area and mean density of the body to achieve uniform image noise of contrast-enhanced pediatric chest CT obtained at variable kV levels and with combined tube current modulation

    International Nuclear Information System (INIS)

    Goo, Hyun Woo

    2011-01-01

    A practical body-size adaptive protocol providing uniform image noise at various kV levels is not available for pediatric CT. To develop a practical contrast-enhanced pediatric chest CT protocol providing uniform image noise by using an individualized volume CT dose index (CTDIvol) determined by the cross-sectional area and density of the body at variable kV levels and with combined tube current modulation. A total of 137 patients (mean age, 7.6 years) underwent contrast-enhanced pediatric chest CT based on body weight. From the CTDIvol, image noise, and area and mean density of the cross-section at the lung base in the weight-based group, the best fit equation was estimated with a very high correlation coefficient (γ 2 = 0.86, P 2 vs. 326.3 ± 124.8 cm 2 ), mean density (-212.9 ± 53.1 HU vs. -221.1 ± 56.3 HU), and image noise (13.8 ± 2.3 vs. 13.6 ± 1.7 HU) between the weight-based and the CTDIvol groups (P > 0.05). Contrast-enhanced pediatric chest CT with the CTDIvol determined individually by the cross-sectional area and density of the body provides more uniform noise and better dose adaptation to body habitus than does weight-based CT at variable kV levels and with combined tube current modulation. (orig.)

  15. Force Modulator System

    Energy Technology Data Exchange (ETDEWEB)

    Redmond Clark

    2009-04-30

    Many metal parts manufacturers use large metal presses to shape sheet metal into finished products like car body parts, jet wing and fuselage surfaces, etc. These metal presses take sheet metal and - with enormous force - reshape the metal into a fully formed part in a manner of seconds. Although highly efficient, the forces involved in forming metal parts also damage the press itself, limit the metals used in part production, slow press operations and, when not properly controlled, cause the manufacture of large volumes of defective metal parts. To date, the metal-forming industry has not been able to develop a metal-holding technology that allows full control of press forces during the part forming process. This is of particular importance in the automotive lightweighting efforts under way in the US automotive manufacturing marketplace. Metalforming Controls Technology Inc. (MC2) has developed a patented press control system called the Force Modulator that has the ability to control these press forces, allowing a breakthrough in stamping process control. The technology includes a series of hydraulic cylinders that provide controlled tonnage at all points in the forming process. At the same time, the unique cylinder design allows for the generation of very high levels of clamping forces (very high tonnages) in very small spaces; a requirement for forming medium and large panels out of HSS and AHSS. Successful production application of these systems testing at multiple stamping operations - including Ford and Chrysler - has validated the capabilities and economic benefits of the system. Although this technology has been adopted in a number of stamping operations, one of the primary barriers to faster adoption and application of this technology in HSS projects is system cost. The cost issue has surfaced because the systems currently in use are built for each individual die as a custom application, thus driving higher tooling costs. This project proposed to better

  16. Photovoltaic module and interlocked stack of photovoltaic modules

    Science.gov (United States)

    Wares, Brian S.

    2014-09-02

    One embodiment relates to an arrangement of photovoltaic modules configured for transportation. The arrangement includes a plurality of photovoltaic modules, each photovoltaic module including a frame. A plurality of individual male alignment features and a plurality of individual female alignment features are included on each frame. Adjacent photovoltaic modules are interlocked by multiple individual male alignment features on a first module of the adjacent photovoltaic modules fitting into and being surrounded by corresponding individual female alignment features on a second module of the adjacent photovoltaic modules. Other embodiments, features and aspects are also disclosed.

  17. Reducing microwave absorption with fast frequency modulation.

    Science.gov (United States)

    Qin, Juehang; Hubler, A

    2017-05-01

    We study the response of a two-level quantum system to a chirp signal, using both numerical and analytical methods. The numerical method is based on numerical solutions of the Schrödinger solution of the two-level system, while the analytical method is based on an approximate solution of the same equations. We find that when two-level systems are perturbed by a chirp signal, the peak population of the initially unpopulated state exhibits a high sensitivity to frequency modulation rate. We also find that the aforementioned sensitivity depends on the strength of the forcing, and weaker forcings result in a higher sensitivity, where the frequency modulation rate required to produce the same reduction in peak population would be lower. We discuss potential applications of this result in the field of microwave power transmission, as it shows applying fast frequency modulation to transmitted microwaves used for power transmission could decrease unintended absorption of microwaves by organic tissue.

  18. The ANTARES optical module

    Energy Technology Data Exchange (ETDEWEB)

    Amram, P.; Anghinolfi, M.; Anvar, S.; Ardellier-Desages, F.E.; Aslanides, E.; Aubert, J.-J.; Azoulay, R.; Bailey, D.; Basa, S.; Battaglieri, M.; Bellotti, R.; Benhammou, Y.; Bernard, F.; Berthier, R.; Bertin, V.; Billault, M.; Blaes, R.; Bland, R.W.; Blondeau, F.; Botton, N. de; Boulesteix, J.; Brooks, C.B.; Brunner, J.; Cafagna, F.; Calzas, A.; Capone, A.; Caponetto, L.; Carloganu, C.; Carmona, E.; Carr, J.; Carton, P.-H.; Cartwright, S.L.; Cassol, F.; Cecchini, S.; Ciacio, F.; Circella, M.; Compere, C.; Cooper, S.; Coyle, P.; Croquette, J.; Cuneo, S.; Danilov, M.; Dantzig, R. van; De Marzo, C.; DeVita, R.; Deck, P.; Destelle, J.-J.; Dispau, G.; Drougou, J.F.; Druillole, F.; Engelen, J.; Feinstein, F.; Festy, D.; Fopma, J.; Gallone, J.-M.; Giacomelli, G.; Goret, P.; Gosset, L.; Gournay, J.-F.; Heijboer, A.; Hernandez-Rey, J.J.; Herrouin, G.; Hubbard, J.R.; Jaquet, M.; Jong, M. de; Karolak, M.; Kooijman, P.; Kouchner, A.; Kudryavtsev, V.A.; Lachartre, D.; Lafoux, H. E-mail: lafoux@cea.fr; Lamare, P.; Languillat, J.-C.; Laubier, L.; Laugier, J.-P.; Le Guen, Y.; Le Provost, H.; Le Van Suu, A.; Lemoine, L.; Lo Nigro, L.; Lo Presti, D.; Loucatos, S.; Louis, F.; Lyashuk, V.; Magnier, P.; Marcelin, M.; Margiotta, A.; Massol, A.; Masullo, R.; Mazeas, F.; Mazeau, B.; Mazure, A.; McMillan, J.E.; Michel, J.L.; Migneco, E.; Millot, C.; Mols, P.; Montanet, F.; Montaruli, T.; Morel, J.P.; Moscoso, L.; Musumeci, M.; Navas, S.; Nezri, E.; Nooren, G.J.; Oberski, J.; Olivetto, C.; Oppelt-Pohl, A.; Palanque-Delabrouille, N.; Papaleo, R.; Payre, P.; Perrin, P.; Petruccetti, M.; Petta, C.; Piattelli, P.; Poinsignon, J.; Potheau, R.; Queinec, Y.; Racca, C.; Raia, G.; Randazzo, N.; Rethore, F.; Riccobene, G.; Ricol, J.-S.; Ripani, M.; Roca-Blay, V.; Rolin, J.F.; Rostovstev, A.; Russo, G.V.; Sacquin, Y.; Salusti, E.; Schuller, J.-P.; Schuster, W.; Soirat, J.-P.; Souvorova, O.; Spooner, N.J.C.; Spurio, M.; Stolarczyk, T.; Stubert, D.; Taiuti, M.; Tao, C.; Tayalati, Y.; Thompson, L.F.

    2002-05-21

    The ANTARES collaboration is building a deep sea neutrino telescope in the Mediterranean Sea. This detector will cover a sensitive area of typically 0.1 km{sup 2} and will be equipped with about 1000 optical modules. Each of these optical modules consists of a large area photomultiplier and its associated electronics housed in a pressure resistant glass sphere. The design of the ANTARES optical module, which is a key element of the detector, has been finalized following extensive R and D studies and is reviewed here in detail.

  19. The ANTARES optical module

    International Nuclear Information System (INIS)

    Amram, P.; Anghinolfi, M.; Anvar, S.; Ardellier-Desages, F.E.; Aslanides, E.; Aubert, J.-J.; Azoulay, R.; Bailey, D.; Basa, S.; Battaglieri, M.; Bellotti, R.; Benhammou, Y.; Bernard, F.; Berthier, R.; Bertin, V.; Billault, M.; Blaes, R.; Bland, R.W.; Blondeau, F.; Botton, N. de; Boulesteix, J.; Brooks, C.B.; Brunner, J.; Cafagna, F.; Calzas, A.; Capone, A.; Caponetto, L.; Carloganu, C.; Carmona, E.; Carr, J.; Carton, P.-H.; Cartwright, S.L.; Cassol, F.; Cecchini, S.; Ciacio, F.; Circella, M.; Compere, C.; Cooper, S.; Coyle, P.; Croquette, J.; Cuneo, S.; Danilov, M.; Dantzig, R. van; De Marzo, C.; DeVita, R.; Deck, P.; Destelle, J.-J.; Dispau, G.; Drougou, J.F.; Druillole, F.; Engelen, J.; Feinstein, F.; Festy, D.; Fopma, J.; Gallone, J.-M.; Giacomelli, G.; Goret, P.; Gosset, L.; Gournay, J.-F.; Heijboer, A.; Hernandez-Rey, J.J.; Herrouin, G.; Hubbard, J.R.; Jaquet, M.; Jong, M. de; Karolak, M.; Kooijman, P.; Kouchner, A.; Kudryavtsev, V.A.; Lachartre, D.; Lafoux, H.; Lamare, P.; Languillat, J.-C.; Laubier, L.; Laugier, J.-P.; Le Guen, Y.; Le Provost, H.; Le Van Suu, A.; Lemoine, L.; Lo Nigro, L.; Lo Presti, D.; Loucatos, S.; Louis, F.; Lyashuk, V.; Magnier, P.; Marcelin, M.; Margiotta, A.; Massol, A.; Masullo, R.; Mazeas, F.; Mazeau, B.; Mazure, A.; McMillan, J.E.; Michel, J.L.; Migneco, E.; Millot, C.; Mols, P.; Montanet, F.; Montaruli, T.; Morel, J.P.; Moscoso, L.; Musumeci, M.; Navas, S.; Nezri, E.; Nooren, G.J.; Oberski, J.; Olivetto, C.; Oppelt-Pohl, A.; Palanque-Delabrouille, N.; Papaleo, R.; Payre, P.; Perrin, P.; Petruccetti, M.; Petta, C.; Piattelli, P.; Poinsignon, J.; Potheau, R.; Queinec, Y.; Racca, C.; Raia, G.; Randazzo, N.; Rethore, F.; Riccobene, G.; Ricol, J.-S.; Ripani, M.; Roca-Blay, V.; Rolin, J.F.; Rostovstev, A.; Russo, G.V.; Sacquin, Y.; Salusti, E.; Schuller, J.-P.; Schuster, W.; Soirat, J.-P.; Souvorova, O.; Spooner, N.J.C.; Spurio, M.; Stolarczyk, T.; Stubert, D.; Taiuti, M.; Tao, C.; Tayalati, Y.; Thompson, L.F.; Tilav, S.; Triay, R.; Valente, V.; Varlamov, I.; Vaudaine, G.; Vernin, P.; Witt Huberts, P. de; Wolf, E. de; Zakharov, V.; Zavatarelli, S.; D Zornoza, J. de; Zuniga, J.

    2002-01-01

    The ANTARES collaboration is building a deep sea neutrino telescope in the Mediterranean Sea. This detector will cover a sensitive area of typically 0.1 km 2 and will be equipped with about 1000 optical modules. Each of these optical modules consists of a large area photomultiplier and its associated electronics housed in a pressure resistant glass sphere. The design of the ANTARES optical module, which is a key element of the detector, has been finalized following extensive R and D studies and is reviewed here in detail

  20. The ANTARES Optical Module

    CERN Document Server

    Amram, P; Anvar, S; Ardellier-Desages, F E; Aslanides, Elie; Aubert, Jean-Jacques; Azoulay, R; Bailey, D; Basa, S; Battaglieri, M; Bellotti, R; Benhammou, Ya; Bernard, F; Berthier, R; Bertin, V; Billault, M; Blaes, R; Bland, R W; Blondeau, F; De Botton, N R; Boulesteix, J; Brooks, B; Brunner, J; Cafagna, F; Calzas, A; Capone, A; Caponetto, L; Cârloganu, C; Carmona, E; Carr, J; Carton, P H; Cartwright, S L; Cassol, F; Cecchini, S; Ciacio, F; Circella, M; Compere, C; Cooper, S; Coyle, P; Croquette, J; Cuneo, S; Danilov, M; Van Dantzig, R; De Marzo, C; De Vita, R; Deck, P; Destelle, J J; Dispau, G; Drougou, J F; Druillole, F; Engelen, J; Feinstein, F; Festy, D; Fopma, J; Gallone, J M; Giacomelli, G; Goret, P; Gosset, L G; Gournay, J F; Heijboer, A; Hernández-Rey, J J; Herrouin, G; Hubbard, John R; Jacquet, M; De Jong, M; Karolak, M; Kooijman, P M; Kouchner, A; Kudryavtsev, V A; Lachartre, D; Lafoux, H; Lamare, P; Languillat, J C; Laubier, L; Laugier, J P; Le Guen, Y; Le Provost, H; Le Van-Suu, A; Lemoine, L; Lo Nigro, L; Lo Presti, D; Loucatos, Sotirios S; Louis, F; Lyashuk, V I; Magnier, P; Marcelin, M; Margiotta, A; Massol, A; Masullo, R; Mazéas, F; Mazeau, B; Mazure, A; McMillan, J E; Michel, J L; Migneco, E; Millot, C; Mols, P; Montanet, François; Montaruli, T; Morel, J P; Moscoso, L; Navas, S; Nezri, E; Nooren, G J L; Oberski, J; Olivetto, C; Oppelt-pohl, A; Palanque-Delabrouille, Nathalie; Payre, P; Perrin, P; Petruccetti, M; Petta, P; Piattelli, P; Poinsignon, J; Popa, V; Potheau, R; Queinec, Y; Racca, C; Raia, G; Randazzo, N; Rethore, F; Riccobene, G; Ricol, J S; Ripani, M; Roca-Blay, V; Rolin, J F; Rostovtsev, A A; Russo, G V; Sacquin, Yu; Salusti, E; Schuller, J P; Schuster, W; Soirat, J P; Suvorova, O; Spooner, N J C; Spurio, M; Stolarczyk, T; Stubert, D; Taiuti, M; Tao, Charling; Tayalati, Y; Thompson, L F; Tilav, S; Triay, R; Valente, V; Varlamov, I; Vaudaine, G; Vernin, P; De Witt-Huberts, P K A; De Wolf, E; Zakharov, V; Zavatarelli, S; De Dios-Zornoza-Gomez, Juan; Zúñiga, J

    2002-01-01

    The ANTARES collaboration is building a deep sea neutrino telescope in the Mediterranean Sea. This detector will cover a sensitive area of typically 0.1 km-squared and will be equipped with about 1000 optical modules. Each of these optical modules consists of a large area photomultiplier and its associated electronics housed in a pressure resistant glass sphere. The design of the ANTARES optical module, which is a key element of the detector, has been finalized following extensive R & D studies and is reviewed here in detail.

  1. Frames in super Hilbert modules

    Directory of Open Access Journals (Sweden)

    Mehdi Rashidi-Kouchi

    2018-01-01

    Full Text Available In this paper, we define super Hilbert module and investigate frames in this space. Super Hilbert modules are  generalization of super Hilbert spaces in Hilbert C*-module setting. Also, we define frames in a super Hilbert module and characterize them by using of the concept of g-frames in a Hilbert C*-module. Finally, disjoint frames in Hilbert C*-modules are introduced and investigated.

  2. Strain-Modulated Epitaxy

    National Research Council Canada - National Science Library

    Brown, April

    1999-01-01

    Strain-Modulated Epitaxy (SME) is a novel approach, invented at Georgia Tech, to utilize subsurface stressors to control strain and therefore material properties and growth kinetics in the material above the stressors...

  3. Solid state detector module

    International Nuclear Information System (INIS)

    Hoffman, D. M.

    1985-01-01

    A solid state detector in which each scintillator is optimally configured and coupled with its associated sensing diode in a way which exploits light piping effects to enhance efficiency, and at the same time provide a detector which is modular in nature. To achieve light piping, the scintillator crystal is oriented such that its sides conform with the crystal cleavage plane, and the sides are highly polished. An array of tungsten collimator plates define the individual channels. Multi-channel scintillator/diode modules are mounted behind and in registry with the plurality of collimator plates. A plurality of scintillators are bonded together after coating the surfaces thereof to minimize optical crosstalk. After lapping the face of the scintillator module, it is then bonded to a diode module with individual scintillators in registration with individual diodes. The module is then positioned in the detector array with collimator plates at the junctions between the scintillators

  4. Nestor optical modules blackening

    International Nuclear Information System (INIS)

    Cordelli, M.; Rutili, A.; Trasatti, L.

    1998-09-01

    The optical modules (OM) containing the photomultiplier tubes (PM) for a deep sea neutrino telescope must be protected them from direct sunlight. The problem has been solved using a heat shrink plastic sheet with very good optical and mechanical properties

  5. Fermilab linac upgrade. Module conditioning results

    International Nuclear Information System (INIS)

    Kroc, T.; Moretti, A.; Popovic, M.

    1992-01-01

    The 805 MHz side-coupled cavity modules for the Fermilab 400 MeV linac upgrade have been conditioned to accept full power. The sparking rate in the cavities and in the side cells has been reduced to acceptable levels. It required approximately 40 x 10 6 pulses for each module to achieve an adequately low sparking rate. This contribution outlines the commissioning procedure, presents the sparking rate improvements and the radiation level improvements through the commissioning process and discusses the near-on-line commissioning plans for this accelerator. (Author) ref., 4 figs

  6. Fermilab Linac Upgrade: Module conditioning results

    International Nuclear Information System (INIS)

    Kroc, T.; Moretti, A.; Popovic, M.

    1992-12-01

    The 805 MHz Side-coupled cavity modules for the Fermilab 400 MeV linac upgrade have been conditioned to accept full power. The sparking rate in the cavities and in the side-cells has been reduced to acceptable levels. It required approximately 40 x 10 6 pulses for each module to achieve an adequately low sparking rate. This contribution outlines the commissioning procedure, presents the sparking rate improvements and the radiation level improvements through the commissioning process and disc the near-online commissioning plans for this accelerator

  7. Programmable synchronous communications module

    International Nuclear Information System (INIS)

    Horelick, D.

    1979-10-01

    The functional characteristics of a programmable, synchronous serial communications CAMAC module with buffering in block format are described. Both bit and byte oriented protocols can be handled in full duplex depending on the program implemented. The main elements of the module are a Signetics 2652 Multi-Protocol Communications Controller, a Zilog Z-808 8 bit microprocessor with PROM and RAM, and FIFOs for buffering

  8. Groups, rings, modules

    CERN Document Server

    Auslander, Maurice

    2014-01-01

    This classic monograph is geared toward advanced undergraduates and graduate students. The treatment presupposes some familiarity with sets, groups, rings, and vector spaces. The four-part approach begins with examinations of sets and maps, monoids and groups, categories, and rings. The second part explores unique factorization domains, general module theory, semisimple rings and modules, and Artinian rings. Part three's topics include localization and tensor products, principal ideal domains, and applications of fundamental theorem. The fourth and final part covers algebraic field extensions

  9. Modulated Current Drive Measurements

    International Nuclear Information System (INIS)

    Petty, C.C.; Lohr, J.; Luce, T.C.; Prater, R.; Cox, W.A.; Forest, C.B.; Jayakumar, R.J.; Makowski, M.A.

    2005-01-01

    A new measurement approach is presented which directly determines the noninductive current profile from the periodic response of the motional Stark effect (MSE) signals to the slow modulation of the external current drive source. A Fourier transform of the poloidal magnetic flux diffusion equation is used to analyze the MSE data. An example of this measurement technique is shown using modulated electron cyclotron current drive (ECCD) discharges from the DIII-D tokamak

  10. Directed network modules

    International Nuclear Information System (INIS)

    Palla, Gergely; Farkas, Illes J; Pollner, Peter; Derenyi, Imre; Vicsek, Tamas

    2007-01-01

    A search technique locating network modules, i.e. internally densely connected groups of nodes in directed networks is introduced by extending the clique percolation method originally proposed for undirected networks. After giving a suitable definition for directed modules we investigate their percolation transition in the Erdos-Renyi graph both analytically and numerically. We also analyse four real-world directed networks, including Google's own web-pages, an email network, a word association graph and the transcriptional regulatory network of the yeast Saccharomyces cerevisiae. The obtained directed modules are validated by additional information available for the nodes. We find that directed modules of real-world graphs inherently overlap and the investigated networks can be classified into two major groups in terms of the overlaps between the modules. Accordingly, in the word-association network and Google's web-pages, overlaps are likely to contain in-hubs, whereas the modules in the email and transcriptional regulatory network tend to overlap via out-hubs

  11. Second generation SLAC modulator

    International Nuclear Information System (INIS)

    Donaldson, A.R.; Cron, J.C.; Hanselman, R.R.

    1986-06-01

    The Stanford Linear Accelerator Laboratory has undertaken the construction of a single pass electron-positron collider. In order to reach required beam energy 235 new klystrons needed upgraded modulator systems. The collider will use 50 GeV electrons and positrons. The increase in accelerator energy from the present 30 GeV necessitates the replacement of existing 35 MW klystrons with new 67 MW units. The doubling of klystron output power required a redesign of the modulator system. The 67 MW klystron needs a 350 kV beam voltage pulse with a 3.7 μs pulse width. A new pulse transformer was designed to deliver the increased voltage and pulse width. Pulse cable design was evaluated to obtain increased reliability of that critical element. The modulator, with the exception of its power supply, was rebuilt to produce the required power increase while enhancing reliability and improving maintainability. An investigation of present thyratron switch tube performance under the new operating conditions resulted in agitation and some warranted panic but these conditions were mitigated after several successful experiments and some evolutionary narrowing of the klystron pulse width. The discussion will cover the upgraded modulator system specifications and some details of the new pulse transformer tank, pulse cable, modulator, and modulator switch tube

  12. Decoupled Modulation Control

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Shaobu; Huang, Renke; Huang, Zhenyu; Diao, Ruisheng

    2016-06-03

    The objective of this research work is to develop decoupled modulation control methods for damping inter-area oscillations with low frequencies, so the damping control can be more effective and easier to design with less interference among different oscillation modes in the power system. A signal-decoupling algorithm was developed that can enable separation of multiple oscillation frequency contents and extraction of a “pure” oscillation frequency mode that are fed into Power System Stabilizers (PSSs) as the modulation input signals. As a result, instead of introducing interferences between different oscillation modes from the traditional approaches, the output of the new PSS modulation control signal mainly affects only one oscillation mode of interest. The new decoupled modulation damping control algorithm has been successfully developed and tested on the standard IEEE 4-machine 2-area test system and a minniWECC system. The results are compared against traditional modulation controls, which demonstrates the validity and effectiveness of the newly-developed decoupled modulation damping control algorithm.

  13. Superstability for Generalized Module Left Derivations and Generalized Module Derivations on a Banach Module (I

    Directory of Open Access Journals (Sweden)

    Rassias JM

    2009-01-01

    Full Text Available We discuss the superstability of generalized module left derivations and generalized module derivations on a Banach module. Let be a Banach algebra and a Banach -module, and . The mappings , and are defined and it is proved that if (resp., is dominated by then is a generalized (resp., linear module- left derivation and is a (resp., linear module- left derivation. It is also shown that if (resp., is dominated by then is a generalized (resp., linear module- derivation and is a (resp., linear module- derivation.

  14. CYP2R1 polymorphisms are important modulators of circulating 25-hydroxyvitamin D levels in elderly females with vitamin insufficiency, but not of the response to vitamin D supplementation.

    Science.gov (United States)

    Arabi, A; Khoueiry-Zgheib, N; Awada, Z; Mahfouz, R; Al-Shaar, L; Hoteit, M; Rahme, M; Baddoura, R; Halabi, G; Singh, R; El Hajj Fuleihan, G

    2017-01-01

    We studied the association between CYP2R1 genetic polymorphisms and circulating 25-hydroxyvitamin D [25(OH)D] before and after supplementation with vitamin D3 in 218 elderly. We found differences between 3 and 8 ng/ml in circulating levels at baseline in women but not in the response after 1 year of supplementation. This study evaluated the association between polymorphisms in four single nucleotide polymorphisms (SNPs) of the CYP2R1 gene and 25(OH)D levels before and 1 year after supplementation with two different doses of vitamin D3 (600 IU daily or a dose equivalent to 3750 IU daily), in a cohort of 218 (96 men and 122 women) Lebanese elderly overweight subjects. Genotyping was performed for rs12794714, rs10741657, rs1562902, and rs10766197 SNPs using real-time PCR. The 25(OH)D levels were measured by liquid chromatography tandem mass spectrometry. At baseline, the mean ± SD age was 71.0 ± 4.7 years, BMI 30.3 ± 4.6 kg/m 2 , and 25(OH)D level was 20.5 ± 7.6 ng/ml. There were significant differences in mean 25(OH)D levels between genotypes in women, but not in men. After adjustment for age, season, and BMI, the homozygous for the low frequency gene variant (HLV) of rs1562902 and rs10741657 SNPs had the highest mean 25(OH)D levels with difference of 7.6 ng/ml for rs1562902 SNP (p D levels with difference of 6 ng/ml for rs10766197 (p = 0.003) and of 4.8 ng/ml (p = 0.02) for rs12794714, compared to the HLV. CYP2R1 genetic polymorphisms explained 4.8 to 9.8 % of variability in 25(OH)D in women. After 1 year, there was no difference in the response to vitamin D3 supplementation between genotypes in either gender. This study showed a difference in 25(OH)D levels between CYP2R1 genotypes that equates a daily supplementation of 400-800 IU vitamin D, depending on genotype. It underscores possible important genetic contributions for the high prevalence of hypovitaminosis D in the Middle East.

  15. Measuring high-frequency responses of an electro-optic phase modulator based on dispersion induced phase modulation to intensity modulation conversion

    Science.gov (United States)

    Zhang, Shangjian; Wang, Heng; Wang, Yani; Zou, Xinhai; Zhang, Yali; Liu, Shuang; Liu, Yong

    2014-11-01

    We investigate the phase modulation to intensity modulation conversion in dispersive fibers for measuring frequency responses of electro-optic phase modulators, and demonstrate two typical measurements with cascade path and fold-back path. The measured results achieve an uncertainty of less than 2.8% within 20 GHz. Our measurements show stable and repeatable results because the optical carrier and its phase-modulated sidebands are affected by the same fiber impairments. The proposed method requires only dispersive fibers and works without any small-signal assumption, which is applicable for swept frequency measurement at different driving levels and operating wavelengths.

  16. Prolonged treatment with transcutaneous electrical nerve stimulation (TENS) modulates neuro-gastric motility and plasma levels of vasoactive intestinal peptide (VIP), motilin and interleukin-6 (IL-6) in systemic sclerosis.

    Science.gov (United States)

    McNearney, Terry A; Sallam, Hanaa S; Hunnicutt, Sonya E; Doshi, Dipti; Chen, Jiande D Z

    2013-01-01

    We assessed the effects of transcutaneous electrical nerve stimulation (TENS) on neurogastric functioning in scleroderma patients. Seventeen SSc patients underwent 30 min TENS treatment >10Hz at GI acupuncture points PC6 and ST36, once (acute TENS) and then after two weeks of TENS sessions for 30 min twice daily (prolonged TENS). Data collected at Visits 1 and 2 included gastric myoelectrical activity (GMA) by surface electrogastrography (EGG), heart rate variability (HRV) by surface electrocardiography (EKG), GI specific symptoms and health related SF-36 questionnaires. Plasma VIP, motilin and IL-6 levels were determined. Statistical analyses were performed by Student's t-test, Spearman Rank and p-values TENS, the percentages of normal slow waves and average slow wave coupling (especially channels 1, 2 reflecting gastric pacemaker and corpus regions) were significantly increased; 2. the percentage of normal slow waves was significantly correlated to sympathovagal balance; 3. Mean plasma VIP and motilin levels were significantly decreased after acute TENS, (vs. baseline), generally maintained in the prolonged TENS intervals. Compared to baseline, mean plasma IL-6 levels were significantly increased after acute TENS, but significantly decreased after prolonged TENS. 4. After prolonged TENS, the frequency of awakening due to abdominal pain and abdominal bloating were significantly and modestly decreased, respectively. In SSc patients, two weeks of daily TENS improved patient GMA scores, lowered plasma VIP, motilin and IL-6 levels and improved association between GMA and sympathovagal balance. This supports the therapeutic potential of prolonged TENS to enhance gastric myoelectrical functioning in SSc.

  17. Phase ramping and modulation of reflectometer signals

    International Nuclear Information System (INIS)

    Conway, G.D.; Bartlett, D.V.; Stoff, P.E.

    1999-01-01

    The phase and amplitude signals of JET heterodyne reflectometers show varying levels of high frequency turbulence superimposed on a slow changing mean. The phase signal also shows multi-radian (> 1 fringe) variations with two quite different time scales (2-10 ms and sub-ms). In both cases the mean reflected power, together with turbulent phase and amplitude fluctuation levels, are modulated synchronously with the are modulated synchronously with the phase fringes. The slow fringes appear to result radial movement of the cutoff layer with the amplitude modulation possibly due to multiple reflection between plasma and wall. The fast fringes occur in intermittent bursts and appear to be phase runaway resulting from antenna misalignment. Using a 2-D physical optics simulation code it is possible to replicate the fast bursts of phase runaway from steady-state turbulence and misaligned antennas. This offers a possible alternative explanation for some of the observations of bursting turbulence seen in reflectometer signals. (authors)

  18. Canons, competencies and critique: delivering an undergraduate entrepreneurial marketing module

    OpenAIRE

    Ardley, Barry; Hardwick, Jialin

    2017-01-01

    In the context of the debate about the status of marketing degrees, graduate knowledge and competencies, this paper reflects on a set of pedagogic issues associated with the delivery of a final level entrepreneurial marketing module. Drawing on key literature, the module takes a set of entrepreneurial marketing canons as the basis of learning. Primary research was conducted into student perceptions of the module based on an interpretative methodology, using an open ended questionnaire. Studen...

  19. Enhanced mutual capture of colored solitons by matched modulator

    Science.gov (United States)

    Feigenbaum, Eyal; Orenstein, Meir

    2004-08-01

    The mutual capture of two colored solitons is enhanced by a modulator, to a level which enables its practical exploitation, e.g., for a read- write mechanism in a soliton buffer. The enhanced capture was analyzed using closed form particle-like soliton perturbation, and verified by numerical simulations. Optimal modulator frequency and modulation depth are obtained. This mutual capture can be utilized for all-optical soliton logic and memory.

  20. Coolant channel module CCM

    International Nuclear Information System (INIS)

    Hoeld, Alois

    2007-01-01

    A complete and detailed description of the theoretical background of an '(1D) thermal-hydraulic drift-flux based mixture-fluid' coolant channel model and its resulting module CCM will be presented. The objective of this module is to simulate as universally as possible the steady state and transient behaviour of the key characteristic parameters of a single- or two-phase fluid flowing within any type of heated or non-heated coolant channel. Due to the possibility that different flow regimes can appear along any channel, such a 'basic (BC)' 1D channel is assumed to be subdivided into a number of corresponding sub-channels (SC-s). Each SC can belong to only two types of flow regime, an SC with just a single-phase fluid, containing exclusively either sub-cooled water or superheated steam, or an SC with a two-phase mixture flow. After an appropriate nodalisation of such a BC (and therefore also its SC-s) a 'modified finite volume method' has been applied for the spatial discretisation of the partial differential equations (PDE-s) which represent the basic conservation equations of thermal-hydraulics. Special attention had to be given to the possibility of variable SC entrance or outlet positions (which describe boiling boundaries or mixture levels) and thus the fact that an SC can even disappear or be created anew. The procedure yields for each SC type (and thus the entire BC), a set of non-linear ordinary 1st order differential equations (ODE-s). To link the resulting mean nodal with the nodal boundary function values, both of which are present in the discretised differential equations, a special quadratic polygon approximation procedure (PAX) had to be constructed. Together with the very thoroughly tested packages for drift-flux, heat transfer and single- and two-phase friction factors this procedure represents the central part of the here presented 'Separate-Region' approach, a theoretical model which provides the basis to the very effective working code package CCM

  1. Klystron Gun Arcing and Modulator Protection

    International Nuclear Information System (INIS)

    Gold, S

    2004-01-01

    The demand for 500 kV and 265 amperes peak to power an X-Band klystron brings up protection issues for klystron faults and the energy dumped into the arc from the modulator. This situation is made worse when more than one klystron will be driven from a single modulator, such as the existing schemes for running two and eight klystrons. High power pulsed klystrons have traditionally be powered by line type modulators which match the driving impedance with the load impedance and therefore current limit at twice the operating current. Multiple klystrons have the added problems of a lower modulator source impedance and added stray capacitance, which converts into appreciable energy at high voltages like 500kV. SLAC has measured the energy dumped into klystron arcs in a single and dual klystron configuration at the 400 to 450 kV level and found interesting characteristics in the arc formation. The author will present measured data from klystron arcs powered from line-type modulators in several configurations. The questions arise as to how the newly designed solid-state modulators, running multiple tubes, will react to a klystron arc and how much energy will be dumped into the arc

  2. Cell shunt resistance and photovoltaic module performance

    Energy Technology Data Exchange (ETDEWEB)

    McMahon, T.J.; Basso, T.S.; Rummel, S.R. [National Renewable Energy Lab., Golden, CO (United States)

    1996-05-01

    Shunt resistance of cells in photovoltaic modules can affect module power output and could indicate flawed manufacturing processes and reliability problems. The authors describe a two-terminal diagnostic method to directly measure the shunt resistance of individual cells in a series-connected module non-intrusively, without deencapsulation. Peak power efficiency vs. light intensity was measured on a 12-cell, series-connected, single crystalline module having relatively high cell shunt resistances. The module was remeasured with 0.5-, 1-, and 2-ohm resistors attached across each cell to simulate shunt resistances of several emerging technologies. Peak power efficiencies decreased dramatically at lower light levels. Using the PSpice circuit simulator, the authors verified that cell shunt and series resistances can indeed be responsible for the observed peak power efficiency vs. intensity behavior. The authors discuss the effect of basic cell diode parameters, i.e., shunt resistance, series resistance, and recombination losses, on PV module performance as a function of light intensity.

  3. Pulse power modulators - an overview

    International Nuclear Information System (INIS)

    Venkatramani, N.

    2006-01-01

    Pulse power modulators are electronic devices to provide, high voltage, high current, power bursts. Ideally, a modulator, with the means to shape and control the pulses, acts as a switch between a high voltage power supply and its load. This article gives an overview of the pulse power modulators: starting with the basics of pulse and modulation, it covers modulation topologies, different types of modulators, major subsystems and pulse measurement techniques. The various applications of pulse power modulators and the recent trends have been included at the end. (author)

  4. Spatial Terahertz Modulator

    Science.gov (United States)

    Xie, Zhenwei; Wang, Xinke; Ye, Jiasheng; Feng, Shengfei; Sun, Wenfeng; Akalin, Tahsin; Zhang, Yan

    2013-11-01

    Terahertz (THz) technology is a developing and promising candidate for biological imaging, security inspection and communications, due to the low photon energy, the high transparency and the broad band properties of the THz radiation. However, a major encountered bottleneck is lack of efficient devices to manipulate the THz wave, especially to modulate the THz wave front. A wave front modulator should allow the optical or electrical control of the spatial transmission (or reflection) of an input THz wave and hence the ability to encode the information in a wave front. Here we propose a spatial THz modulator (STM) to dynamically control the THz wave front with photo-generated carriers. A computer generated THz hologram is projected onto a silicon wafer by a conventional spatial light modulator (SLM). The corresponding photo-generated carrier spatial distribution will be induced, which forms an amplitude hologram to modulate the wave front of the input THz beam. Some special intensity patterns and vortex beams are generated by using this method. This all-optical controllable STM is structure free, high resolution and broadband. It is expected to be widely used in future THz imaging and communication systems.

  5. Integrated unaligned resonant modulator tuning

    Energy Technology Data Exchange (ETDEWEB)

    Zortman, William A.; Lentine, Anthony L.

    2017-10-03

    Methods and systems for tuning a resonant modulator are disclosed. One method includes receiving a carrier signal modulated by the resonant modulator with a stream of data having an approximately equal number of high and low bits, determining an average power of the modulated carrier signal, comparing the average power to a predetermined threshold, and operating a tuning device coupled to the resonant modulator based on the comparison of the average power and the predetermined threshold. One system includes an input structure, a plurality of processing elements, and a digital control element. The input structure is configured to receive, from the resonant modulator, a modulated carrier signal. The plurality of processing elements are configured to determine an average power of the modulated carrier signal. The digital control element is configured to operate a tuning device coupled to the resonant modulator based on the average power of the modulated carrier signal.

  6. Intracellular cholesterol level regulates sensitivity of glioblastoma cells against temozolomide-induced cell death by modulation of caspase-8 activation via death receptor 5-accumulation and activation in the plasma membrane lipid raft.

    Science.gov (United States)

    Yamamoto, Yutaro; Tomiyama, Arata; Sasaki, Nobuyoshi; Yamaguchi, Hideki; Shirakihara, Takuya; Nakashima, Katsuhiko; Kumagai, Kosuke; Takeuchi, Satoru; Toyooka, Terushige; Otani, Naoki; Wada, Kojiro; Narita, Yoshitaka; Ichimura, Koichi; Sakai, Ryuichi; Namba, Hiroki; Mori, Kentaro

    2018-01-01

    Development of resistance against temozolomide (TMZ) in glioblastoma (GBM) after continuous treatment with TMZ is one of the critical problems in clinical GBM therapy. Intracellular cholesterol regulates cancer cell biology, but whether intracellular cholesterol is involved in TMZ resistance of GBM cells remains unclear. The involvement of intracellular cholesterol in acquired resistance against TMZ in GBM cells was investigated. Intracellular cholesterol levels were measured in human U251 MG cells with acquired TMZ resistance (U251-R cells) and TMZ-sensitive control U251 MG cells (U251-Con cells), and found that the intracellular cholesterol level was significantly lower in U251-R cells than in U251-Con cells. In addition, treatment by intracellular cholesterol remover, methyl-beta cyclodextrin (MβCD), or intracellular cholesterol inducer, soluble cholesterol (Chol), regulated TMZ-induced U251-Con cell death in line with changes in intracellular cholesterol level. Involvement of death receptor 5 (DR5), a death receptor localized in the plasma membrane, was evaluated. TMZ without or with MβCD and/or Chol caused accumulation of DR5 into the plasma membrane lipid raft and formed a complex with caspase-8, an extrinsic caspase cascade inducer, reflected in the induction of cell death. In addition, treatment with caspase-8 inhibitor or knockdown of DR5 dramatically suppressed U251-Con cell death induced by combination treatment with TMZ, MβCD, and Chol. Combined treatment of Chol with TMZ reversed the TMZ resistance of U251-R cells and another GBM cell model with acquired TMZ resistance, whereas clinical antihypercholesterolemia agents at physiological concentrations suppressed TMZ-induced cell death of U251-Con cells. These findings suggest that intracellular cholesterol level affects TMZ treatment of GBM mediated via a DR5-caspase-8 mechanism. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Methyl CpG level at distal part of heat-shock protein promoter HSP70 exhibits epigenetic memory for heat stress by modulating recruitment of POU2F1-associated nucleosome-remodeling deacetylase (NuRD) complex.

    Science.gov (United States)

    Kisliouk, Tatiana; Cramer, Tomer; Meiri, Noam

    2017-05-01

    Depending on its stringency, exposure to heat in early life leads to either resilience or vulnerability to heat stress later in life. We hypothesized that epigenetic alterations in genes belonging to the cell proteostasis pathways are attributed to long-term responses to heat stress. Epigenetic regulation of the mRNA expression of the molecular chaperone heat-shock protein (HSP) 70 (HSPA2) was evaluated in the chick hypothalamus during the critical period of thermal-control establishment on day 3 post-hatch and during heat challenge on day 10. Both the level and duration of HSP70 expression during heat challenge a week after heat conditioning were more pronounced in chicks conditioned under harsh versus mild temperature. Analyzing different segments of the promoter in vitro indicated that methylation of a distal part altered its transcriptional activity. In parallel, DNA-methylation level of this segment in vivo was higher in harsh- compared to mild-heat-conditioned chicks. Hypermethylation of the HSP70 promoter in high-temperature-conditioned chicks was accompanied by a reduction in both POU Class 2 Homeobox 1 (POU2F1) binding and recruitment of the nucleosome remodeling deacetylase (NuRD) chromatin-remodeling complex. As a result, histone H3 acetylation levels at the HSP70 promoter were higher in harsh-temperature-conditioned chicks than in their mild-heat-conditioned counterparts. These results suggest that methylation level of a distal part of the HSP70 promoter and POU2F1 recruitment may reflect heat-stress-related epigenetic memory and may be useful in differentiating between individuals that are resilient or vulnerable to stress. © 2017 International Society for Neurochemistry.

  8. Analysis of trace levels of impurities and hydrogen isotopes in helium purge gas using gas chromatography for tritium extraction system of an Indian lead lithium ceramic breeder test blanket module.

    Science.gov (United States)

    Devi, V Gayathri; Sircar, Amit; Yadav, Deepak; Parmar, Jayraj

    2018-01-12

    In the fusion fuel cycle, the accurate analysis and understanding of the chemical composition of any gas mixture is of great importance for the efficient design of a tritium extraction and purification system or any tritium handling system. Methods like laser Raman spectroscopy and gas chromatography with thermal conductivity detector have been considered for hydrogen isotopes analyses in fuel cycles. Gas chromatography with a cryogenic separation column has been used for the analysis of hydrogen isotopes gas mixtures in general due to its high reliability and ease of operation. Hydrogen isotopes gas mixture analysis with cryogenic columns has been reported earlier using different column materials for percentage level composition. In the present work, trace levels of hydrogen isotopes (∼100 ppm of H 2 and D 2 ) have been analyzed with a Zeolite 5A and a modified γ-Al 2 O 3 column. Impurities in He gas (∼10 ppm of H 2 , O 2 , and N 2 ) have been analyzed using a Zeolite 13-X column. Gas chromatography with discharge ionization detection has been utilized for this purpose. The results of these experiments suggest that the columns developed were able to separate ppm levels of the desired components with a small response time (<6 min) and good resolution in both cases. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Power module assembly

    Science.gov (United States)

    Campbell, Jeremy B [Torrance, CA; Newson, Steve [Redondo Beach, CA

    2011-11-15

    A power module assembly of the type suitable for deployment in a vehicular power inverter, wherein the power inverter has a grounded chassis, is provided. The power module assembly comprises a conductive base layer electrically coupled to the chassis, an insulating layer disposed on the conductive base layer, a first conductive node disposed on the insulating layer, a second conductive node disposed on the insulating layer, wherein the first and second conductive nodes are electrically isolated from each other. The power module assembly also comprises a first capacitor having a first electrode electrically connected to the conductive base layer, and a second electrode electrically connected to the first conductive node, and further comprises a second capacitor having a first electrode electrically connected to the conductive base layer, and a second electrode electrically connected to the second conductive node.

  10. Waveform Sampler CAMAC Module

    International Nuclear Information System (INIS)

    Freytag, D.R.; Haller, G.M.; Kang, H.; Wang, J.

    1985-09-01

    A Waveform Sampler Module (WSM) for the measurement of signal shapes coming from the multi-hit drift chambers of the SLAC SLC detector is described. The module uses a high speed, high resolution analog storage device (AMU) developed in collaboration between SLAC and Stanford University. The AMU devices together with high speed TTL clocking circuitry are packaged in a hybrid which is also suitable for mounting on the detector. The module is in CAMAC format and provides eight signal channels, each recording signal amplitude versus time in 512 cells at a sampling rate of up to 360 MHz. Data are digitized by a 12-bit ADC with a 1 μs conversion time and stored in an on-board memory accessible through CAMAC

  11. GREET Pretreatment Module

    Energy Technology Data Exchange (ETDEWEB)

    Adom, Felix K. [Argonne National Lab. (ANL), Argonne, IL (United States). Energy Systems Division; Dunn, Jennifer B. [Argonne National Lab. (ANL), Argonne, IL (United States). Energy Systems Division; Han, Jeongwoo [Argonne National Lab. (ANL), Argonne, IL (United States). Energy Systems Division

    2014-09-01

    A wide range of biofuels and biochemicals can be produced from cellulosic biomass via different pretreatment technologies that yield sugars. Process simulations of dilute acid and ammonia fiber expansion pretreatment processes and subsequent hydrolysis were developed in Aspen Plus for four lignocellulosic feedstocks (corn stover, miscanthus, switchgrass, and poplar). This processing yields sugars that can be subsequently converted to biofuels or biochemical. Material and energy consumption data from Aspen Plus were then compiled in a new Greenhouses Gases, Regulated Emissions, and Energy Use in Transportation (GREETTM) pretreatment module. The module estimates the cradle-to-gate fossil energy consumption (FEC) and greenhouse gas (GHG) emissions associated with producing fermentable sugars. This report documents the data and methodology used to develop this module and the cradle-to-gate FEC and GHG emissions that result from producing fermentable sugars.

  12. Light Microscopy Module (LMM)-Emulator

    Science.gov (United States)

    Levine, Howard G.; Smith, Trent M.; Richards, Stephanie E.

    2016-01-01

    The Light Microscopy Module (LMM) is a microscope facility developed at Glenn Research Center (GRC) that provides researchers with powerful imaging capability onboard the International Space Station (ISS). LMM has the ability to have its hardware recongured on-orbit to accommodate a wide variety of investigations, with the capability of remotely acquiring and downloading digital images across multiple levels of magnication.

  13. Single Nucleotide Polymorphisms in Noncoding Regions of Rad51C Do Not Change the Risk of Unselected Breast Cancer but They Modulate the Level of Oxidative Stress and the DNA Damage Characteristics

    DEFF Research Database (Denmark)

    Gresner, Peter; Gromadzinska, Jolanta; Jablonska, Ewa

    2014-01-01

    affect the unselected BrC risk. Contrary to this, carriers of rs12946522, rs16943176, rs12946397 and rs17222691 rare-alleles were found to present significantly increased level of blood plasma TBARS compared to respective wild-type homozygotes (p... decreased fraction of oxidatively generated DNA damage (34% of total damaged DNA) in favor of DNA strand breakage, with no effect on total DNA damage, unlike respective wild-types, among which more evenly distributed proportions between oxidatively damaged DNA (48% of total DNA damage) and DNA strand...

  14. CAMAC system test module

    International Nuclear Information System (INIS)

    Dawson, W.K.; Gjovig, A.; Naivar, F.; Potter, J.; Smith, W.

    1981-01-01

    Since the CAMAC Branch Highway is used to both send information to and receive information from a CAMAC crate, faults in this highway can be difficult to recognize and diagnose. Similarly faults caused by a Crate Controller corrupting either instructions or data are difficult to distinguish from faults caused by the modules themselves. The CLIVIT (CAMAC Logic Integrity Via Interactive Testing) module is designed to largely eliminate such difficulties and ambiguities by allowing the verification of Branch Highway and Dataway transactions via an independent data communication path. The principle of operation of the CLIVIT is explained. Described are the prototype construction, testing and use

  15. Instant node package module

    CERN Document Server

    Ali, Juzer

    2013-01-01

    Get to grips with a new technology, understand what it is and what it can do for you, and then get to work with the most important features and tasks. A practical exploration of the lifecycle of creating node modules as well as learning all of the top features that npm has to offer.Intended for readers who want to create their first node.js modules. The programming paradigm of JavaScript is not covered so a foundation in these concepts would be beneficial.

  16. Flexible programmable logic module

    Science.gov (United States)

    Robertson, Perry J.; Hutchinson, Robert L.; Pierson, Lyndon G.

    2001-01-01

    The circuit module of this invention is a VME board containing a plurality of programmable logic devices (PLDs), a controlled impedance clock tree, and interconnecting buses. The PLDs are arranged to permit systolic processing of a problem by offering wide data buses and a plurality of processing nodes. The board contains a clock reference and clock distribution tree that can drive each of the PLDs with two critically timed clock references. External clock references can be used to drive additional circuit modules all operating from the same synchronous clock reference.

  17. Local sleep spindle modulations in relation to specific memory cues

    NARCIS (Netherlands)

    Cox, R.; Hofman, W.F.; de Boer, M.; Talamini, L.M.

    2014-01-01

    Sleep spindles have been connected to memory processes in various ways. In addition, spindles appear to be modulated at the local cortical network level. We investigated whether cueing specific memories during sleep leads to localized spindle modulations in humans. During learning of word-location

  18. Photovoltaic module and interlocked stack of photovoltaic modules

    Science.gov (United States)

    Wares, Brian S.

    2012-09-04

    One embodiment relates to an arrangement of photovoltaic modules configured for transportation. The arrangement includes a plurality of photovoltaic modules, each photovoltaic module including a frame having at least a top member and a bottom member. A plurality of alignment features are included on the top member of each frame, and a plurality of alignment features are included on the bottom member of each frame. Adjacent photovoltaic modules are interlocked by the alignment features on the top member of a lower module fitting together with the alignment features on the bottom member of an upper module. Other embodiments, features and aspects are also disclosed.

  19. Receiver bandwidth effects on complex modulation and detection using directly modulated lasers.

    Science.gov (United States)

    Yuan, Feng; Che, Di; Shieh, William

    2016-05-01

    Directly modulated lasers (DMLs) have long been employed for short- and medium-reach optical communications due to their low cost. Recently, a new modulation scheme called complex modulated DMLs has been demonstrated showing a significant optical signal to noise ratio sensitivity enhancement compared with the traditional intensity-only detection scheme. However, chirp-induced optical spectrum broadening is inevitable in complex modulated systems, which may imply a need for high-bandwidth receivers. In this Letter, we study the impact of receiver bandwidth effects on the performance of complex modulation and coherent detection systems based on DMLs. We experimentally demonstrate that such systems exhibit a reasonable tolerance for the reduced receiver bandwidth. For 10 Gbaud 4-level pulse amplitude modulation signals, the required electrical bandwidth is as low as 8.5 and 7.5 GHz for 7% and 20% forward error correction, respectively. Therefore, it is feasible to realize DML-based complex modulated systems using cost-effective receivers with narrow bandwidth.

  20. Supplementation of branched-chain amino acids in protein-restricted diets modulates the expression levels of amino acid transporters and energy metabolism associated regulators in the adipose tissue of growing pigs

    Directory of Open Access Journals (Sweden)

    Yinghui Li

    2016-03-01

    Full Text Available This experiment was conducted to investigate the effects of branched-chain amino acids (BCAA supplemented in protein-restricted diets on the growth performance and the expression profile of amino acid transporters and energy metabolism related regulators in the white adipose tissue (WAT of different regional depots including dorsal subcutaneous adipose (DSA and abdominal subcutaneous adipose (ASA. A total of 24 crossbred barrows (7.40 ± 0.70 kg were randomly divided into 4 groups and were fed the following isocaloric diets for 33 days: 1 a recommended adequate protein diet (AP, 20% CP, as a positive control; 2 a low protein diet (LP, 17% CP; 3 the LP diet supplemented with BCAA (LP + B, 17% CP to reach the same level of the AP diet group; 4 the LP diet supplemented with 2 times the amount of BCAA (LP + 2B, 17% CP. The daily gain and daily feed intake of the LP diet group were the lowest among all the treatments (P  0.05. Moreover, BCAA supplementation down-regulated the expression levels of amino acid transporters including L-type amino acid transporter 1 and sodium-coupled neutral amino acid transporter 2 in DSA, but up-regulated the expression level of L-type amino acid transporter 4 in ASA (P < 0.05. Meanwhile, the energy sensor AMP-activated protein kinase α was activated in the DSA of pigs fed LP diet and in the ASA of the pigs fed AP or LP + 2B diets (P < 0.05. The mRNA expression profile of the selected mitochondrial component and mitochondrial biogenesis associated regulators in DSA and ASA also responded differently to dietary BCAA supplementation. These results suggested that the growth performance of growing pigs fed protein restricted diets supplemented with BCAA could catch up to that of the pigs fed AP diets. The results also partly demonstrated that the regulation mechanisms of BCAA are different in the adipose tissues of different depots.