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Sample records for activation reverses kainate-induced

  1. Kainate-induced network activity in the anterior cingulate cortex.

    Science.gov (United States)

    Shinozaki, R; Hojo, Y; Mukai, H; Hashizume, M; Murakoshi, T

    2016-06-14

    Anterior cingulate cortex (ACC) plays a pivotal role in higher order processing of cognition, attention and emotion. The network oscillation is considered an essential means for integration of these CNS functions. The oscillation power and coherence among related areas are often dis-regulated in several psychiatric and pathological conditions with a hemispheric asymmetric manner. Here we describe the network-based activity of field potentials recorded from the superficial layer of the mouse ACC in vitro using submerged type recordings. A short activation by kainic acid administration to the preparation induced populational activities ranging over several frequency bands including theta (3-8Hz), alpha (8-12Hz), beta (13-30Hz), low gamma (30-50Hz) and high gamma (50-80Hz). These responses were repeatable and totally abolished by tetrodotoxin, and greatly diminished by inhibitors of ionotropic and metabotropic glutamate receptors, GABAA receptor or gap-junctions. These observations suggest that the kainate-induced network activity can be a useful model of the network oscillation in the ACC circuit. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. The dextromethorphan analog dimemorfan attenuates kainate-induced seizures via σ1 receptor activation: comparison with the effects of dextromethorphan

    Science.gov (United States)

    Shin, Eun-Joo; Nah, Seung-Yeol; Kim, Won-Ki; Ko, Kwang Ho; Jhoo, Wang-Kee; Lim, Yong-Kwang; Cha, Joo Young; Chen, Chieh-Fu; Kim, Hyoung-Chun

    2005-01-01

    In a previous study, we demonstrated that a dextromethorphan analog, dimemorfan, has neuroprotective effects. Dextromethorphan and dimemorfan are high-affinity ligands at σ1 receptors. Dextromethorphan has moderate affinities for phencyclidine sites, while dimemorfan has very low affinities for such sites, suggesting that these sites are not essential for the anticonvulsant actions of dimemorfan. Kainate (KA) administration (10 mg kg−1, i.p.) produced robust convulsions lasting 4–6 h in rats. Pre-treatment with dimemorfan (12 or 24 mg kg−1) reduced seizures in a dose-dependent manner. Dimemorfan pre-treatment also attenuated the KA-induced increases in c-fos/c-jun expression, activator protein (AP)-1 DNA-binding activity, and loss of cells in the CA1 and CA3 fields of the hippocampus. These effects of dimemorfan were comparable to those of dextromethorphan. The anticonvulsant action of dextromethorphan or dimemorfan was significantly counteracted by a selective σ1 receptor antagonist BD 1047, suggesting that the anticonvulsant action of dextromethorphan or dimemorfan is, at least in part, related to σ1 receptor-activated modulation of AP-1 transcription factors. We asked whether dimemorfan produces the behavioral side effects seen with dextromethorphan or dextrorphan (a phencyclidine-like metabolite of dextromethorphan). Conditioned place preference and circling behaviors were significantly increased in mice treated with phencyclidine, dextrorphan or dextromethorphan, while mice treated with dimemorfan showed no behavioral side effects. Our results suggest that dimemorfan is equipotent to dextromethorphan in preventing KA-induced seizures, while it may lack behavioral effects, such as psychotomimetic reactions. PMID:15723099

  3. Zinc movement in the brain under kainate-induced seizures.

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    Takeda, Atsushi; Hirate, Maki; Tamano, Haruna; Oku, Naoto

    2003-05-01

    On the basis of the evidence that elimination of 65Zn from the brain of epilepsy (EL) mice is facilitated by induction of seizures, zinc movement in the brain was studied in mice injected with kainate (12 mg/kg x 3), which exhibited status epilepticus within 120 min after the last injection of kainate. Zinc concentrations in the brain were determined 24 h after the last injection of kainate. Zinc concentrations in the hippocampus, amygdala and cerebral cortex, in which zinc-containing glutamatergic neuron terminals exist, were significantly decreased by the treatment with kainate, while that in the cerebellum was not decreased. Timm's stain in the brain was extensively attenuated 24 h after the last injection of kainate. These results indicate that zinc homeostasis in the brain is affected by kainate-induced seizures. In the hippocampus of rats injected with kainate (10 mg/kg), furthermore, the release of zinc and glutamate into the extracellular fluid was studied using in vivo microdialysis. The levels of zinc and glutamate in the perfusate were increased along with seizure severity after injection of kainate. It is likely that zinc concentration in the synaptic vesicles is decreased by the excess excitation of glutamatergic neurons. The present study suggests that the excessive release of zinc and glutamate from the neuron terminals under kainate-induced seizures is associated with the loss of zinc from the brain.

  4. Neuropeptide Y-stimulated [(35) S]GTPγs functional binding is reduced in the hippocampus after kainate-induced seizures in mice

    DEFF Research Database (Denmark)

    Elbrønd-Bek, Heidi; Olling, Janne Damm; Gøtzsche, Casper René

    2014-01-01

    , in this study, we explored functional NPY receptor activity in the mouse hippocampus and neocortex after kainate-induced seizures using NPY-stimulated [(35) S]GTPγS binding. Moreover, we also studied levels of [(125) I]-peptide YY (PYY) binding and NPY, Y1, Y2, and Y5 receptor mRNA in these kainate-treated mice...

  5. Co-induction of p75(NTR) and the associated death executor NADE in degenerating hippocampal neurons after kainate-induced seizures in the rat.

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    Yi, Jung-Sun; Lee, Soon-Keum; Sato, Taka-Aki; Koh, Jae-Young

    2003-08-21

    Zinc induces in cultured cortical neurons both p75(NTR) and p75(NTR)-associated death executor (NADE), which together contribute to caspase-dependent neuronal apoptosis. Since zinc neurotoxicity may contribute to neuronal death following seizures, we examined whether p75(NTR) and NADE are co-induced also in rat hippocampal neurons degenerating after seizures. Staining of brain sections with a zinc-specific fluorescent dye (N-(6-methoxy-8-quinolyl)-p-carboxybenzoylsulphonamide) and acid fuchsin revealed zinc accumulation in degenerating neuronal cell bodies in CA1 and CA3 of hippocampus 24 h after kainate injection. Both anti-p75(NTR) and anti-NADE immunoreactivities appeared in zinc-accumulating/degenerating neurons in both areas. Intraventricular injection of CaEDTA, without altering the severity or time course of kainate-induced seizures, markedly attenuated the induction of p75(NTR)/NADE in hippocampus, which correlated with the decrease of caspase-3 activation and zinc accumulation/cell death. The present study has demonstrated that p75(NTR) and NADE are co-induced in neurons degenerating after kainate-induced seizures in rats, likely in a zinc-dependent manner.

  6. Visualization of spatiotemporal energy dynamics of hippocampal neurons by mass spectrometry during a kainate-induced seizure.

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    Yuki Sugiura

    Full Text Available We report the use of matrix-assisted laser desorption/ionization (MALDI imaging mass spectrometry combined with capillary electrophoresis (CE mass spectrometry to visualize energy metabolism in the mouse hippocampus by imaging energy-related metabolites. We show the distribution patterns of ATP, ADP, and AMP in the hippocampus as well as changes in their amounts and distribution patterns in a murine model of limbic, kainate-induced seizure. As an acute response to kainate administration, we found massive and moderate reductions in ATP and ADP levels, respectively, but no significant changes in AMP levels--especially in cells of the CA3 layer. The results suggest the existence of CA3 neuron-selective energy metabolism at the anhydride bonds of ATP and ADP in the hippocampal neurons during seizure. In addition, metabolome analysis of energy synthesis pathways indicates accelerated glycolysis and possibly TCA cycle activity during seizure, presumably due to the depletion of ATP. Consistent with this result, the observed energy depletion significantly recovered up to 180 min after kainate administration. However, the recovery rate was remarkably low in part of the data-pixel population in the CA3 cell layer region, which likely reflects acute and CA3-selective neural death. Taken together, the present approach successfully revealed the spatiotemporal energy metabolism of the mouse hippocampus at a cellular resolution--both quantitatively and qualitatively. We aim to further elucidate various metabolic processes in the neural system.

  7. Elimination of zinc-65 from the brain under kainate-induced seizures.

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    Takeda, Atsushi; Hirate, Maki; Oku, Naoto

    2004-04-01

    On the basis of the previous evidence that 65Zn concentrations in the brain of EL (epilepsy) mice was affected by induction of seizures, 65Zn movement in the brain was quantitatively evaluated in ddY mice treated with kainate. Six days after intravenous injection of 65ZnCl2, mice were intraperitoneally injected with kainate (10 mg/kg x 6 times in 2 weeks). Myoclonic jerks were observed during treatment with kainate. Twenty days after 65Zn injection, 65Zn distribution in the brain was compared between the kainite-treated and control mice. 65Zn distribution in the brain of the kainate-treated mice was overall lower than in the control mice. 65Zn concentration was significantly decreased in the frontal cortex, hippocampal CA1, thalamus and hypothalamus by treatment with kainate. These results demonstrate that kainate-induced seizures are linked to decreased zinc concentrations in the brain.

  8. A new potential AED, carisbamate, substantially reduces spontaneous motor seizures in rats with kainate-induced epilepsy

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    Grabenstatter, Heidi L.; Dudek, F. Edward

    2010-01-01

    Purpose Animal models with spontaneous epileptic seizures may be useful in the discovery of new antiepileptic drugs (AEDs). The purpose of the present study was to evaluate the efficacy of carisbamate on spontaneous motor seizures in rats with kainate-induced epilepsy. Methods Repeated, low-dose (5 mg/kg), intraperitoneal injections of kainate were administered every hour until each male Sprague-Dawley rat had experienced convulsive status epilepticus for at least 3 h. Five 1-month trials (n= 8–10 rats) assessed the effects of 0.3, 1, 3, 10 and 30 mg/kg carisbamate on spontaneous seizures. Each trial involved six AED-versus-vehicle tests comprised of carisbamate or 10% solutol-HS-15 treatments administered as intraperitoneal injections on alternate days with a recovery day between each treatment day. Results Carisbamate significantly reduced motor seizure frequency at doses of 10 and 30 mg/kg, and caused complete seizure cessation during the 6-h post-drug epoch in 7 of 8 animals at 30 mg/kg. The effects of carisbamate (0.3–30 mg/kg) on spontaneous motor seizures appeared dose dependent. Conclusions These data support the hypothesis that a repeated-measures, cross-over protocol in animal models with spontaneous seizures is an effective method for testing AEDs. Carisbamate reduced the frequency of spontaneous motor seizures in a dose-dependent manner, and was more effective than topiramate at reducing seizures in rats with kainate-induced epilepsy. PMID:18494790

  9. Effects of pilocarpine and kainate-induced seizures on N-methyl-d-aspartate receptor gene expression in the rat hippocampus

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    Przewlocka, B.; Labuz, D.; Machelska, H.; Przewlocki, R.; Turchan, J.; Lason, W. [Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow (Poland)

    1997-04-14

    The effects of pilocarpine- and kainate-induced seizures on N-methyl-d-aspartate receptor subunit-1 messenger RNA and [{sup 3}H]dizocilpine maleate binding were studied in the rat hippocampal formation. Pilocarpine- but not kainate-induced seizures decreased N-methyl-d-aspartate receptor subunit-1 messenger RNA level in dentate gyrus at 24 and 72 h after drug injection. Both convulsants decreased the messenger RNA level in CA1 pyramidal cells at 24 and 72 h, the effects of kainate being more profound. Kainate also decreased the N-methyl-d-aspartate receptor subunit-1 messenger RNA level in CA3 region after 24 and 72 h, whereas pilocarpine decreased the messenger RNA level at 72 h only. At 3 h after kainate, but not pilocarpine, an increased binding of [{sup 3}H]dizocilpine maleate in several apical dendritic fields of pyramidal cells was found. Pilocarpine reduced the [{sup 3}H]dizocilpine maleate binding in stratum lucidum only at 3 and 24 h after the drug injection. Pilocarpine but not kainate induced prolonged decrease in N-methyl-d-aspartate receptor subunit-1 gene expression in dentate gyrus. However, at the latest time measured, kainate had the stronger effect in decreasing both messenger RNA N-methyl-d-aspartate receptor subunit-1 and [{sup 3}H]dizocilpine maleate binding in CA1 and CA3 hippocampal pyramidal cells. The latter changes corresponded, however, to neuronal loss and may reflect higher neurotoxic potency of kainate.These data point to some differences in hippocampal N-methyl-d-aspartate receptor regulation in pilocarpine and kainate models of limbic seizures. Moreover, our results suggest that the N-methyl-d-aspartate receptor subunit-1 messenger RNA level is more susceptible to limbic seizures than is [{sup 3}H]dizocilpine maleate binding in the rat hippocampal formation. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

  10. Effects of pilocarpine and kainate-induced seizures on N-methyl-d-aspartate receptor gene expression in the rat hippocampus

    International Nuclear Information System (INIS)

    Przewlocka, B.; Labuz, D.; Machelska, H.; Przewlocki, R.; Turchan, J.; Lason, W.

    1997-01-01

    The effects of pilocarpine- and kainate-induced seizures on N-methyl-d-aspartate receptor subunit-1 messenger RNA and [ 3 H]dizocilpine maleate binding were studied in the rat hippocampal formation. Pilocarpine- but not kainate-induced seizures decreased N-methyl-d-aspartate receptor subunit-1 messenger RNA level in dentate gyrus at 24 and 72 h after drug injection. Both convulsants decreased the messenger RNA level in CA1 pyramidal cells at 24 and 72 h, the effects of kainate being more profound. Kainate also decreased the N-methyl-d-aspartate receptor subunit-1 messenger RNA level in CA3 region after 24 and 72 h, whereas pilocarpine decreased the messenger RNA level at 72 h only. At 3 h after kainate, but not pilocarpine, an increased binding of [ 3 H]dizocilpine maleate in several apical dendritic fields of pyramidal cells was found. Pilocarpine reduced the [ 3 H]dizocilpine maleate binding in stratum lucidum only at 3 and 24 h after the drug injection. Pilocarpine but not kainate induced prolonged decrease in N-methyl-d-aspartate receptor subunit-1 gene expression in dentate gyrus. However, at the latest time measured, kainate had the stronger effect in decreasing both messenger RNA N-methyl-d-aspartate receptor subunit-1 and [ 3 H]dizocilpine maleate binding in CA1 and CA3 hippocampal pyramidal cells. The latter changes corresponded, however, to neuronal loss and may reflect higher neurotoxic potency of kainate.These data point to some differences in hippocampal N-methyl-d-aspartate receptor regulation in pilocarpine and kainate models of limbic seizures. Moreover, our results suggest that the N-methyl-d-aspartate receptor subunit-1 messenger RNA level is more susceptible to limbic seizures than is [ 3 H]dizocilpine maleate binding in the rat hippocampal formation. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

  11. Red Ginseng Extract Attenuates Kainate-Induced Excitotoxicity by Antioxidative Effects

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    Jin-Yi Han

    2012-01-01

    Full Text Available This study investigated the neuroprotective activity of red ginseng extract (RGE, Panax ginseng, C. A. Meyer against kainic acid- (KA- induced excitotoxicity in vitro and in vivo. In hippocampal cells, RGE inhibited KA-induced excitotoxicity in a dose-dependent manner as measured by the MTT assay. To study the possible mechanisms of the RGE-mediated neuroprotective effect against KA-induced cytotoxicity, we examined the levels of intracellular reactive oxygen species (ROS and [Ca2+]i in cultured hippocampal neurons and found that RGE treatment dose-dependently inhibited intracellular ROS and [Ca2+]i elevation. Oral administration of RGE (30 and 200 mg/kg in mice decreased the malondialdehyde (MDA level induced by KA injection (30 mg/kg, i.p.. In addition, similar results were obtained after pretreatment with the radical scavengers Trolox and N, N′-dimethylthiourea (DMTU. Finally, after confirming the protective effect of RGE on hippocampal brain-derived neurotropic factor (BDNF protein levels, we found that RGE is active compounds mixture in KA-induced hippocampal mossy-fiber function improvement. Furthermore, RGE eliminated 1,1-diphenyl-2-picrylhydrazyl (DPPH radicals, and the IC50 was approximately 10 mg/ml. The reductive activity of RGE, as measured by reaction with hydroxyl radical (•OH, was similar to trolox. The second-order rate constant of RGE for •OH was 3.5–4.5×109 M−1·S−1. Therefore, these results indicate that RGE possesses radical reduction activity and alleviates KA-induced excitotoxicity by quenching ROS in hippocampal neurons.

  12. Changes in calcium and iron levels in the brains of rats during kainate induced epilepsy

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    Ren, Min-Qin; Ong, Wei-Yi; Makjanic, Jagoda; Watt, Frank

    1999-10-01

    Epilepsy is a recurrent disorder of cerebral function characterised by sudden brief attacks of altered consciousness, motor activity or sensory phenomena, and affects approximately 1% of the population. Kainic acid injection induces neuronal degeneration in rats, is associated with glial hypertrophy and proliferation in the CA3-CA4 fields of hippocampal complex, and is a model for temporal lobe epilepsy. In this study we have applied Nuclear Microscopy to the investigation of the elemental changes within the hippocampus and the cortex areas of the rat brain following kainate injection. Analyses of unstained freeze dried tissue sections taken at 1 day and 1, 2, 3 and 4 weeks following injection were carried out using the Nuclear Microscopy facility at the Research Centre for Nuclear Microscopy, National University of Singapore. Quantitative analysis and elemental mapping indicates that there are significant changes in the calcium levels and distributions in the hippocampus as early as 1 day following injection. Preliminary results indicate a rapid increase in cellular calcium. High levels of calcium can activate calcium dependent proteins and phospholipases. Activation of phospholipase A 2 can be harmful to surrounding neurons through free radical damage. In addition to observed increases in calcium, there was evidence of increases in iron levels. This is consistent with measurements in other degenerative brain disorders, and may signal a late surge in free radical production.

  13. Changes in calcium and iron levels in the brains of rats during kainate induced epilepsy

    International Nuclear Information System (INIS)

    Ren, M.-Q.; Ong, W.-Y.; Makjanic, Jagoda; Watt, Frank

    1999-01-01

    Epilepsy is a recurrent disorder of cerebral function characterised by sudden brief attacks of altered consciousness, motor activity or sensory phenomena, and affects approximately 1% of the population. Kainic acid injection induces neuronal degeneration in rats, is associated with glial hypertrophy and proliferation in the CA3-CA4 fields of hippocampal complex, and is a model for temporal lobe epilepsy. In this study we have applied Nuclear Microscopy to the investigation of the elemental changes within the hippocampus and the cortex areas of the rat brain following kainate injection. Analyses of unstained freeze dried tissue sections taken at 1 day and 1, 2, 3 and 4 weeks following injection were carried out using the Nuclear Microscopy facility at the Research Centre for Nuclear Microscopy, National University of Singapore. Quantitative analysis and elemental mapping indicates that there are significant changes in the calcium levels and distributions in the hippocampus as early as 1 day following injection. Preliminary results indicate a rapid increase in cellular calcium. High levels of calcium can activate calcium dependent proteins and phospholipases. Activation of phospholipase A 2 can be harmful to surrounding neurons through free radical damage. In addition to observed increases in calcium, there was evidence of increases in iron levels. This is consistent with measurements in other degenerative brain disorders, and may signal a late surge in free radical production

  14. Cell cycle-dependent regulation of kainate-induced inward currents in microglia

    International Nuclear Information System (INIS)

    Yamada, Jun; Sawada, Makoto; Nakanishi, Hiroshi

    2006-01-01

    Microglia are reported to have α-amino-hydroxy-5-methyl-isoxazole-4-propionate/kainate (KA) types. However, only small population of primary cultured rat microglia (approximately 20%) responded to KA. In the present study, we have attempted to elucidate the regulatory mechanism of responsiveness to KA in GMIR1 rat microglial cell line. When the GMIR1 cells were plated at a low density in the presence of granulocyte macrophage colony-stimulating factor, the proliferation rate increased and reached the peak after 2 days in culture and then gradually decreased because of density-dependent inhibition. At cell proliferation stage, approximately 80% of the GMIR1 cells exhibited glutamate (Glu)- and KA-induced inward currents at cell proliferation stage, whereas only 22.5% of the cells showed responsiveness to Glu and KA at cell quiescent stage. Furthermore, the mean amplitudes of inward currents induced by Glu and KA at cell proliferation stage (13.8 ± 3.0 and 8.4 ± 0.6 pA) were significantly larger than those obtained at cell quiescent stage (4.7 ± 0.8 and 6.2 ± 1.2 pA). In the GMIR1 cells, KA-induced inward currents were markedly inhibited by (RS)-3-(2-carboxybenzyl) willardiine (UBP296), a selective antagonist for KA receptors. The KA-responsive cells also responded to (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA), a selective agonist for GluR5, in both GMIR1 cells and primary cultured rat microglia. Furthermore, mRNA levels of the KA receptor subunits, GluR5 and GluR6, at the cell proliferation stage were significantly higher than those at the cell quiescent stage. Furthermore, the immunoreactivity for GluR6/7 was found to increase in activated microglia in the post-ischemic hippocampus. These results strongly suggest that microglia have functional KA receptors mainly consisting of GluR5 and GluR6, and the expression levels of these subunits are closely regulated by the cell cycle mechanism

  15. The dextromethorphan analog dimemorfan attenuates kainate-induced seizures via σ1 receptor activation: comparison with the effects of dextromethorphan

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    Shin, Eun-Joo; Nah, Seung-Yeol; Kim, Won-Ki; Ko, Kwang Ho; Jhoo, Wang-Kee; Lim, Yong-Kwang; Cha, Joo Young; Chen, Chieh-Fu; Kim, Hyoung-Chun

    2005-01-01

    In a previous study, we demonstrated that a dextromethorphan analog, dimemorfan, has neuroprotective effects.Dextromethorphan and dimemorfan are high-affinity ligands at σ1 receptors. Dextromethorphan has moderate affinities for phencyclidine sites, while dimemorfan has very low affinities for such sites, suggesting that these sites are not essential for the anticonvulsant actions of dimemorfan.Kainate (KA) administration (10 mg kg−1, i.p.) produced robust convulsions lasting 4–6 h in rats. P...

  16. Low-frequency stimulation in anterior nucleus of thalamus alleviates kainate-induced chronic epilepsy and modulates the hippocampal EEG rhythm.

    Science.gov (United States)

    Wang, Yi; Liang, Jiao; Xu, Cenglin; Wang, Ying; Kuang, Yifang; Xu, Zhenghao; Guo, Yi; Wang, Shuang; Gao, Feng; Chen, Zhong

    2016-02-01

    High-frequency stimulation (HFS) of the anterior nucleus of thalamus (ANT) is a new and alternative option for the treatment of intractable epilepsy. However, the responder rate is relatively low. The present study was designed to determine the effect of low-frequency stimulation (LFS) in ANT on chronic spontaneous recurrent seizures and related pathological pattern in intra-hippocampal kainate mouse model. We found that LFS (1 Hz, 100 μs, 300 μA), but not HFS (100 Hz, 100 μs, 30 μA), in bilateral ANT significantly decreased the frequency of spontaneous recurrent seizures, either non-convulsive focal seizures or tonic-clonic generalized seizures. The anti-epileptic effect persisted for one week after LFS cessation, which manifested as a long-term inhibition of the frequency of seizures with short (20-60 s) and intermediate duration (60-120 s). Meanwhile, LFS decreased the frequency of high-frequency oscillations (HFOs) and interictal spikes, two indicators of seizure severity, whereas HFS increased the HFO frequency. Furthermore, LFS decreased the power of the delta band and increased the power of the gamma band of hippocampal background EEG. In addition, LFS, but not HFS, improved the performance of chronic epileptic mice in objection-location task, novel objection recognition and freezing test. These results provide the first evidence that LFS in ANT alleviates kainate-induced chronic epilepsy and cognitive impairment, which may be related to the modulation of the hippocampal EEG rhythm. This may be of great therapeutic significance for clinical treatment of epilepsy with deep brain stimulation. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. The effect of Vitamin E on learning and memory deficits in intrahippocampal kainate-induced temporal lobe epilepsy in rats.

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    Kiasalari, Zahra; Khalili, Mohsen; Shafiee, Samaneh; Roghani, Mehrdad

    2016-01-01

    Since temporal lobe epilepsy (TLE) is associated with learning and memory impairment, we investigated the beneficial effect of Vitamin E on the impaired learning and memory in the intrahippocampal kainate model of TLE in rats. Rats were divided into sham, Vitamin E-treated sham, kainate, and Vitamin E-treated kainate. Intrahippocampal kainate was used for induction of epilepsy. Vitamin E was injected intraperitoneal (i.p.) at a dose of 200 mg/kg/day started 1 week before surgery until 1 h presurgery. Initial and step-through latencies in the passive avoidance test and alternation behavior percentage in Y-maze were finally determined in addition to measurement of some oxidative stress markers. Kainate injection caused a higher severity and rate of seizures and deteriorated learning and memory performance in passive avoidance paradigm and spontaneous alternation as an index of spatial recognition memory in Y-maze task. Intrahippocampal kainate also led to the elevation of malondialdehyde (MDA) and nitrite and reduced activity of superoxide dismutase (SOD). Vitamin E pretreatment significantly attenuated severity and incidence rate of seizures, significantly improved retrieval and recall in passive avoidance, did not ameliorate spatial memory deficit in Y-maze, and lowered MDA and enhanced SOD activity. Vitamin E improves passive avoidance learning and memory and part of its beneficial effect is due to its potential to mitigate hippocampal oxidative stress.

  18. Muscular activation during reverse and non-reverse chewing cycles in unilateral posterior crossbite.

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    Piancino, Maria Grazia; Farina, Dario; Talpone, Francesca; Merlo, Andrea; Bracco, Pietro

    2009-04-01

    The aim of this study was to characterize the kinematics and masseter muscle activation in unilateral posterior crossbite. Eighty-two children (8.6 +/- 1.3 yr of age) with unilateral posterior crossbite and 12 children (8.9 +/- 0.6 yr of age) with normal occlusion were selected for the study. Electromyography (EMG) and kinematics were concurrently recorded during mastication of a soft bolus and a hard bolus. The percentage of reverse cycles in the group of patients was 59.0 +/- 33.1% (soft bolus) and 69.7 +/- 29.7% (hard bolus) when chewing on the crossbite side. When chewing on the non-affected side, the number of reverse cycles was 16.7 +/- 24.5% (soft bolus) and 16.7 +/- 22.3% (hard bolus). The reverse cycles on the crossbite side were narrower with respect to the cycles on the non-affected side. Although both types of cycles in patients resulted in lower EMG activity of the masseter of the crossbite side than of the contralateral masseter, the activity of the non-affected side was larger for reverse than for non-reverse cycles. It was concluded that when chewing on the crossbite side, the masseter activity is reduced on the mastication side (crossbite) and is unaltered (non-reverse cycles) or increased (reverse) on the non-affected side.

  19. An Impact of Reverse Logistics Activities on Marketing Communication

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    František Milichovský

    2017-01-01

    Full Text Available The topic of reverse logistics has become very actual due the requirements of highly competitive market. This importance is made by significance of condition for environment-friendly production and purchasing around the world. Individual activities, which are included in reverse logistics, support entrepreneurs in their competitiveness to other companies and to own customers. The objective of the paper is to find relationship between marketing communication tool and activities of reverse logistics on behaviour of final customers in Czech Republic. A theoretical background from the area of reverse logistics supports this approach with data from primary research collected by the author. A data from primary research was used. The entire primary research focused on the evaluation of customers’ perception in the area of reverse logistics in the Czech Republic by a questionnaire survey. Sample population was created by 1266 consumers’ respondents, which were chosen in random way. There were returned questionnaires from 332 respondents. Questionnaire itself was distributed by only platform, during June 2016. The research itself was aimed at a random chosen group of people in the Czech Republic. Findings of the research shows connection of individual activities of reverse logistics and individual communication tools, which are well-accepted on customer side. The result of the research can be used for the companies that operate in the Czech or Central European market.

  20. Effect of endurance training on seizure susceptibility, behavioral changes and neuronal damage after kainate-induced status epilepticus in spontaneously hypertensive rats.

    Science.gov (United States)

    Tchekalarova, J; Shishmanova, M; Atanasova, D; Stefanova, M; Alova, L; Lazarov, N; Georgieva, K

    2015-11-02

    The therapeutic efficacy of regular physical exercises in an animal model of epilepsy and depression comorbidity has been confirmed previously. In the present study, we examined the effects of endurance training on susceptibility to kainate (KA)-induced status epilepticus (SE), behavioral changes and neuronal damage in spontaneously hypertensive rats (SHRs). Male SHRs were randomly divided into two groups. One group was exercised on a treadmill with submaximal loading for four weeks and the other group was sedentary. Immediately after the training period, SE was evoked in half of the sedentary and trained rats by KA, while the other half of the two groups received saline. Basal systolic (SP), diastolic (DP) and mean arterial pressure (MAP) of all rats were measured at the beginning and at the end of the training period. Anxiety, memory and depression-like behaviour were evaluated a month after SE. The release of 5-HT in the hippocampus was measured using a liquid scintillation method and neuronal damage was analyzed by hematoxylin and eosin staining. SP and MAP of exercised SHRs decreased in comparison with the initial values. The increased resistance of SHRs to KA-induced SE was accompanied by an elongated latent seizure-free period, improved object recognition memory and antidepressant effect after the training program. While the anticonvulsant and positive behavioral effects of endurance training were accompanied by an increase of 5-HT release in the hippocampus, it did not exert neuroprotective activity. Our results indicate that prior exercise is an effective means to attenuate KA-induced seizures and comorbid behavioral changes in a model of hypertension and epilepsy suggesting a potential influence of hippocampal 5-HT on a comorbid depression. However, this beneficial impact does not prevent the development of epilepsy and concomitant brain damage. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Thermally activated magnetization reversal in magnetic tunnel junctions

    International Nuclear Information System (INIS)

    Guang-Hong, Zhou; Yin-Gang, Wang; Xian-Jin, Qi; Zi-Quan, Li; Jian-Kang, Chen

    2009-01-01

    In this paper, the magnetization reversal of the ferromagnetic layers in the IrMn/CoFe/AlO x /CoFe magnetic tunnel junction has been investigated using bulk magnetometry. The films exhibit very complex magnetization processes and reversal mechanism. Thermal activation phenomena such as the training effect, the asymmetry of reversal, the loop broadening and the decrease of exchange field while holding the film at negative saturation have been observed on the hysteresis loops of the pinned ferromagnetic layer while not on those of the free ferromagnetic layer. The thermal activation phenomena observed can be explained by the model of two energy barrier distributions with different time constants. (condensed matter: electronic structure, electrical, magnetic, and optical properties)

  2. Anticonvulsant effect of AMP by direct activation of adenosine A1 receptor.

    Science.gov (United States)

    Muzzi, Mirko; Coppi, Elisabetta; Pugliese, Anna Maria; Chiarugi, Alberto

    2013-12-01

    Purinergic neurotransmission mediated by adenosine (Ado) type 1 receptors (A1Rs) plays pivotal roles in negative modulation of epileptic seizures, and Ado is thought to be a key endogenous anticonvulsant. Recent evidence, however, indicates that AMP, the metabolic precursor of Ado, also activate A1Rs. Here, we evaluated the antiepileptic effects of AMP adopting in vitro and in vivo models of epilepsy. We report that AMP reversed the increase in population spike (PS) amplitude and the decrease in PS latency induced by a Mg(2+)-free extracellular solution in CA1 neurons of mouse hippocampal slices. The AMP effects were inhibited by the A1R antagonist DPCPX, but not prevented by inhibiting conversion of AMP into Ado, indicating that AMP inhibited per se sustained hippocampal excitatory neurotransmission by directly activating A1Rs. AMP also reduced seizure severity and mortality in a model of audiogenic convulsion. Of note, the anticonvulsant effects of AMP were potentiated by preventing its conversion into Ado and inhibited by DPCPX. When tested in a model of kainate-induced seizure, AMP prolonged latency of convulsions but had no effects on seizure severity and mortality. Data provide the first evidence that AMP is an endogenous anticonvulsant acting at A1Rs. © 2013.

  3. Wavefront reversal in a copper vapor active medium

    Energy Technology Data Exchange (ETDEWEB)

    Bunkin, F.V.; Savranskii, V.V.; Shafeev, G.A.

    1981-09-01

    Wavefront reversal in the resonator of a copper vapor laser was observed. The frequencies of the signal and reversed waves were the same. The dependence of the reversed signal power on the input signal power had a threshold. Photographs were obtained of the reconstructed image of an object when a distorting phase plate was inserted in the resonator.

  4. XIAP reverses various functional activities of FRNK in endothelial cells

    International Nuclear Information System (INIS)

    Ahn, Sunyoung; Kim, Hyun Jeong; Chi, Sung-Gil; Park, Heonyong

    2012-01-01

    Highlights: ► FRNK domain is recruited into focal adhesion (FA), controlling endothelial cell adhesion. ► XIAP binds the FRNK domain of FAK. ► XIAP inhibits recruitment of FRNK into Fas and FRNK-promoted cell adhesion. ► XIAP plays a key role in vascular functions of FRNK or FRNK domain-mediated vascular functions of FAK. -- Abstract: In endothelial cells, focal adhesion kinase (FAK) regulates cell proliferation, migration, adhesion, and shear-stimulated activation of MAPK. We recently found that FAK is recruited into focal adhesion (FA) sites through interactions with XIAP (X-chromosome linked inhibitor of apoptosis protein) and activated by Src kinase in response to shear stress. In this study, we examined which domain(s) of FAK is(are) important for various vascular functions such as FA recruiting, XIAP-binding and shear stress-stimulated ERK activation. Through a series of experiments, we determined that the FRNK domain is recruited into FA sites and promotes endothelial cell adhesion. Interestingly, XIAP knockdown was shown to reduce FA recruitment of FRNK and the cell adhesive effect of FRNK. In addition, we found that XIAP interacts with FRNK, suggesting cross-talk between XIAP and FRNK. We also demonstrated that FRNK inhibits endothelial cell migration and shear-stimulated ERK activation. These inhibitory effects of FRNK were reversed by XIAP knockdown. Taken together, we can conclude that XIAP plays a key role in vascular functions of FRNK or FRNK domain-mediated vascular functions of FAK.

  5. Diffusion properties of active particles with directional reversal

    International Nuclear Information System (INIS)

    Großmann, R; Bär, M; Peruani, F

    2016-01-01

    The diffusion properties of self-propelled particles which move at constant speed and, in addition, reverse their direction of motion repeatedly are investigated. The internal dynamics of particles triggering these reversal processes is modeled by a stochastic clock. The velocity correlation function as well as the mean squared displacement is investigated and, furthermore, a general expression for the diffusion coefficient for self-propelled particles with directional reversal is derived. Our analysis reveals the existence of an optimal, finite rotational noise amplitude which maximizes the diffusion coefficient. We comment on the relevance of these results with regard to biological systems and suggest further experiments in this context. (paper)

  6. HALT & REVERSE: Hsf1 activators lower cardiomyocyt damage; towards a novel approach to REVERSE atrial fibrillation.

    Science.gov (United States)

    Lanters, Eva A H; van Marion, Denise M S; Kik, Charles; Steen, Herman; Bogers, Ad J J C; Allessie, Maurits A; Brundel, Bianca J J M; de Groot, Natasja M S

    2015-11-05

    Atrial fibrillation is a progressive arrhythmia, the exact mechanism underlying the progressive nature of recurrent AF episodes is still unknown. Recently, it was found that key players of the protein quality control system of the cardiomyocyte, i.e. Heat Shock Proteins, protect against atrial fibrillation progression by attenuating atrial electrical and structural remodeling (electropathology). HALT & REVERSE aims to investigate the correlation between electropathology, as defined by endo- or epicardial mapping, Heat Shock Protein levels and development or recurrence of atrial fibrillation following pulmonary vein isolation, or electrical cardioversion or cardiothoracic surgery. This study is a prospective observational study. Three separate study groups are defined: (1) cardiothoracic surgery, (2) pulmonary vein isolation and (3) electrical cardioversion. An intra-operative high-resolution epicardial (group 1) or endocardial (group 2) mapping procedure of the atria is performed to study atrial electropathology. Blood samples for Heat Shock Protein determination are obtained at baseline and during the follow-up period at 3 months (group 2), 6 months (groups 1 and 2) and 1 year (group 1 and 2). Tissue samples of the right and left atrial appendages in patients in group 1 are analysed for Heat Shock Protein levels and for tissue characteristics. Early post procedural atrial fibrillation is detected by continuous rhythm monitoring, whereas late post procedural atrial fibrillation is documented by either electrocardiogram or 24-h Holter registration. HALT & REVERSE aims to identify the correlation between Heat Shock Protein levels and degree of electropathology. The study outcome will contribute to novel diagnostic tools for the early recognition of clinical atrial fibrillation. Rotterdam Medical Ethical Committee MEC-2014-393, Dutch Trial Registration NTR4658.

  7. Influence of gold nanoparticles of varying size in improving the lipase activity within cationic reverse micelles.

    Science.gov (United States)

    Maiti, Subhabrata; Das, Dibyendu; Shome, Anshupriya; Das, Prasanta Kumar

    2010-02-08

    Herein, we report the effect of gold nanoparticles (GNPs) in enhancing lipase activity in reverse micelles of cetyltrimethylammonium bromide (CTAB)/water/isooctane/n-hexanol. The size and concentration of the nanoparticles were varied and their specific roles were assessed in detail. An overall enhancement of activity was observed in the GNP-doped CTAB reverse micelles. The improvement in activity becomes more prominent with increasing concentration and size of the GNPs (0-52 microM and ca. 3-30 nm, respectively). The observed highest lipase activity (k(2)=1070+/-12 cm(3) g(-1) s(-1)) in GNP-doped CTAB reverse micelles ([GNP]: 52 microm, ca. 20 nm) is 2.5-fold higher than in CTAB reverse micelles without GNPs. Improvement in the lipase activity is only specific to the GNP-doped reverse micellar media, whereas GNP deactivates and structurally deforms the enzyme in aqueous media. The reason for this activation is probably due to the formation of larger-sized reverse micelles in which the GNP acts as a polar core and the surfactants aggregate around the nanoparticle ('GNP pool') instead of only water. Lipase at the augmented interface of the GNP-doped reverse micelle showed improved activity because of enhancement in both the substrate and enzyme concentrations and increased flexibility in the lipase conformation. The extent of the activation is greater in the case of the larger-sized GNPs. A correlation has been established between the activity of lipase and its secondary structure by using circular dichroism and FTIR spectroscopic analysis. The generalized influence of GNP is verified in the reverse micelles of another surfactant, namely, cetyltripropylammonium bromide (CTPAB). TEM, dynamic light scattering (DLS), and UV/Vis spectroscopic analysis were utilized to characterize the GNPs and the organized aggregates. For the first time, CTAB-based reverse micelles have been found to be an excellent host for lipase simply by doping with appropriately sized GNPs.

  8. The active and passive kinematic difference between primary reverse and total shoulder prostheses

    NARCIS (Netherlands)

    Alta, T.D.; de Toledo, J.S.; Veeger, H.E.J.; Janssen, T.W.J.; Willems, W.J.

    2014-01-01

    Background: Reverse shoulder arthroplasty (RSA) and total shoulder arthroplasty (TSA) effectively decrease pain and improve clinical outcome. However, indications and biomechanical properties vary greatly. Our aim was to analyze both active and passive shoulder motion (thoracohumeral [TH],

  9. Compact toroid development: activity plan for field reversed configurations

    International Nuclear Information System (INIS)

    1984-06-01

    This document contains the description, goals, status, plans, and approach for the investigation of the properties of a magnetic configuration for plasma confinement identified as the field reversed configuration (FRC). This component of the magnetic fusion development program has been characterized by its potential for physical compactness and a flexible range of output power. The included material represents the second phase of FRC program planning. The first was completed in February 1983, and was reported in DOE/ER-0160; Compact Toroid Development. This planning builds on that previous report and concentrates on the detailed plans for the next several years of the current DOE sponsored program. It has been deliberately restricted to the experimental and theoretical efforts possible within the present scale of effort. A third phase of this planning exercise will examine the subsequent effort and resources needed to achieve near term (1987 to 1990) FRC technical objectives

  10. Coenzyme Q10 instilled as eye drops on the cornea reaches the retina and protects retinal layers from apoptosis in a mouse model of kainate-induced retinal damage.

    Science.gov (United States)

    Lulli, Matteo; Witort, Ewa; Papucci, Laura; Torre, Eugenio; Schipani, Christian; Bergamini, Christian; Dal Monte, Massimo; Capaccioli, Sergio

    2012-12-17

    To evaluate if coenzyme Q10 (CoQ10) can protect retinal ganglion cells (RGCs) from apoptosis and, when instilled as eye drops on the cornea, if it can reach the retina and exert its antiapoptotic activity in this area in a mouse model of kainate (KA)-induced retinal damage. Rat primary or cultured RGCs were subjected to glutamate (50 μM) or chemical hypoxia (Antimycin A, 200 μM) or serum withdrawal (FBS, 0.5%) in the presence or absence of CoQ10 (10 μM). Cell viability was evaluated by light microscopy and fluorescence-activated cell sorting analyses. Apoptosis was evaluated by caspase 3/7 activity and mitochondrion depolarization tetramethylrhodamine ethyl ester analysis. CoQ10 transfer to the retina following its instillation as eye drops on the cornea was quantified by HPLC. Retinal protection by CoQ10 (10 μM) eye drops instilled on the cornea was then evaluated in a mouse model of KA-induced excitotoxic retinal cell apoptosis by cleaved caspase 3 immunohistofluorescence, caspase 3/7 activity assays, and quantification of inhibition of RGC loss. CoQ10 significantly increased viable cells by preventing RGC apoptosis. Furthermore, when topically applied as eye drops to the cornea, it reached the retina, thus substantially increasing local CoQ10 concentration and protecting retinal layers from apoptosis. The ability of CoQ10 eye drops to protect retinal cells from apoptosis in the mouse model of KA-induced retinal damage suggests that topical CoQ10 may be evaluated in designing therapies for treating apoptosis-driven retinopathies.

  11. Two proteins with reverse transcriptase activities associated with hepatitis B virus-like particles

    International Nuclear Information System (INIS)

    Bavand, M.R.; Laub, O.

    1988-01-01

    Recent studies suggest that hepatitis B virus (HBV), despite being a DNA virus, replicates via an RNA intermediate. The HBV life cycle is therefore a permuted version of the RNA retroviral life cycle. Sequence homology between retroviral reverse transcriptase and the putative HBV polymerase gene product suggests the presence of an HBV reverse transcriptase. As yet, there has been no direct evidence that reverse transcriptase activity is present in the viral particle. The authors used activity gel analysis to detect the in situ catalytic activities of DNA polymerases after sodium dodecyl sulfate-polyacrylamide gel electrophorsis. These studies demonstrated that HBV-like particles secreted by a differentiated human hepatoma cell line tranfected with genomic HBV DNA contain two major polymerase activities which migrate as ∼90- and ∼70-kilodalton (kDa) proteins. This demonstrated, for the first time, that HBV-like particles contain a novel DNA polymerase-reverse transcriptase activity. Furthermore, they propose that the 70-kDa reverse transcriptase may be produced by proteolytic self-cleavage of the 90-kDa precursor protein

  12. Reversal of metabolic disorders by pharmacological activation of bile acid receptors TGR5 and FXR

    Directory of Open Access Journals (Sweden)

    Kavita Jadhav

    2018-03-01

    Full Text Available Objectives: Activation of the bile acid (BA receptors farnesoid X receptor (FXR or G protein-coupled bile acid receptor (GPBAR1; TGR5 improves metabolic homeostasis. In this study, we aim to determine the impact of pharmacological activation of bile acid receptors by INT-767 on reversal of diet-induced metabolic disorders, and the relative contribution of FXR vs. TGR5 to INT-767's effects on metabolic parameters. Methods: Wild-type (WT, Tgr5−/−, Fxr−/−, Apoe−/− and Shp−/− mice were used to investigate whether and how BA receptor activation by INT-767, a semisynthetic agonist for both FXR and TGR5, could reverse diet-induced metabolic disorders. Results: INT-767 reversed HFD-induced obesity dependent on activation of both TGR5 and FXR and also reversed the development of atherosclerosis and non-alcoholic fatty liver disease (NAFLD. Mechanistically, INT-767 improved hypercholesterolemia by activation of FXR and induced thermogenic genes via activation of TGR5 and/or FXR. Furthermore, INT-767 inhibited several lipogenic genes and de novo lipogenesis in the liver via activation of FXR. We identified peroxisome proliferation-activated receptor γ (PPARγ and CCAAT/enhancer-binding protein α (CEBPα as novel FXR-regulated genes. FXR inhibited PPARγ expression by inducing small heterodimer partner (SHP whereas the inhibition of CEBPα by FXR was SHP-independent. Conclusions: BA receptor activation can reverse obesity, NAFLD, and atherosclerosis by specific activation of FXR or TGR5. Our data suggest that, compared to activation of FXR or TGR5 only, dual activation of both FXR and TGR5 is a more attractive strategy for treatment of common metabolic disorders. Keywords: Farnesoid X receptor, TGR5, Atherosclerosis, Obesity, NAFLD

  13. Anticancer and reversing multidrug resistance activities of natural isoquinoline alkaloids and their structure-activity relationship.

    Science.gov (United States)

    Qing, Zhi-Xing; Huang, Jia-Lu; Yang, Xue-Yi; Liu, Jing-Hong; Cao, Hua-Liang; Xiang, Feng; Cheng, Pi; Zeng, Jian-Guo

    2017-09-20

    The severe anticancer situation as well as the emergence of multidrug-resistant (MDR) cancer cells has created an urgent need for the development of novel anticancer drugs with different mechanisms of action. A large number of natural alkaloids, such as paclitaxel, vinblastine and camptothecin have already been successfully developed into chemotherapy agents. Following the success of these natural products, in this review, twenty-six types of isoquinoline alkaloid (a total of 379 alkaloids), including benzyltetrahydroisoquinoline, aporphine, oxoaporphine, isooxoaporphine, dimeric aporphine, bisbenzylisoquinoline, tetrahydroprotoberberine, protoberberine, protopine, dihydrobenzophenanthridine, benzophenanthridine, benzophenanthridine dimer, ipecac, simple isoquinoline, pavine, montanine, erythrina, chelidonine, tropoloisoquinoline, azafluoranthene, phthalideisoquinoline, naphthylisoquinoline, lycorine, crinane, narciclasine, and phenanthridone, were summarized based on their cytotoxic and MDR reversing activities against various cancer cells. Additionally, the structure-activity relationships of different types of isoquinoline alkaloid were also discussed. Interestingly, some aporphine, oxoaporphine, isooxoaporphine, bisbenzylisoquinoline, and protoberberine alkaloids display more potent anticancer activities or anti-MDR effects than positive control against the tested cancer cells and are regarded as attractive targets for discovery new anticancer drugs or lead compounds. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Polarization reversal during the solar noise storm activity of August 1971

    International Nuclear Information System (INIS)

    Kurihara, Masahiro

    1975-01-01

    Reversals of the sense of circular polarization of solar radio emission were observed for active type I storms in August 1971. Observations with a 160-MHz interferometer revealed that the reversals were caused by sudden growth and decay of a secondary storm source whose sense of polarization was opposite to that of the long-lasting main source. The time variations of both the associated S-component sources and sunspots are compared with that of the storm sources. The role of the magnetic field, which presumably connects the storm sources, the S-component sources, and the sunspots, is discussed in relation to the origin of the storm activity. (author)

  15. Reversal of androgen inhibition of estrogen-activated sexual behavior by cholinergic agents.

    Science.gov (United States)

    Dohanich, G P; Cada, D A

    1989-12-01

    Androgens have been found to inhibit lordosis activated by estrogen treatment of ovariectomized female rats. In the present experiments, dihydrotestosterone propionate (200 micrograms for 3 days) inhibited the incidence of lordosis in ovariectomized females treated with estradiol benzoate (1 microgram for 3 days). This inhibition of lordosis was reversed 15 min after bilateral intraventricular infusion of physostigmine (10 micrograms/cannula), an acetylcholinesterase inhibitor, or carbachol (0.5 microgram/cannula), a cholinergic receptor agonist. This reversal of inhibition appears to be mediated by cholinergic muscarinic receptors since pretreatment with scopolamine (4 mg/kg, ip), a muscarinic receptor blocker, prevented the reversal of androgen inhibition by physostigmine. These results indicate that androgens may inhibit estrogen-activated lordosis through interference with central cholinergic muscarinic mechanisms.

  16. Active control of internal transport barrier and confinement database in JT-60U reversed shear plasma

    Energy Technology Data Exchange (ETDEWEB)

    Sakamoto, Yoshiteru; Takizuka, Tomonori; Shirai, Hiroshi; Fujita, Takaaki; Kamada, Yutaka; Ide, Shunsuke; Fukuda, Takeshi; Koide, Yoshihiko [Japan Atomic Energy Research Inst., Naka, Ibaraki (Japan). Naka Fusion Research Establishment

    2001-07-01

    Active control of internal transport barrier (ITB) and confinement properties of plasma with ITB have been studied in reversed shear plasmas. Modifications of the radial electric field (E{sub r}) profile by changing the combination of tangential neutral beams can control the ITB strength, where the contribution to E{sub r} from the toroidal rotation plays an important role. The ITB confinement database of reversed shear plasmas has been constructed. Stored energy is strongly correlated with poloidal magnetic field at the ITB foot. (author)

  17. Neuron activity in rat hippocampus and motor cortex during discrimination reversal.

    Science.gov (United States)

    Disterhoft, J F; Segal, M

    1978-01-01

    Chronic unit activity and gross movement were recorded from rats during two discrimination reversals in a classical appetitive conditioning situation. The anticipatory movement decreased in response to the former CS+ tone and increased to the previous CS- tone after each reversal. Hippocampus and motor cortex were differently related to these two kinds of behavioral change. Response rates of hippocampal neurons were more closely related to the increased movement response to the former CS- which now signaled food. Motor cortex neuron responses were more closely correlated with the decrease in movement responses to the former CS+ which became neutral after the reversal. It appeared that hippocampal neurons could have been involved in one cognitive aspect of the situation, motor cortex neurons in another. The data were related to current functional concepts of these brain regions.

  18. Plasma Membrane ATPase Activity following Reversible and Irreversible Freezing Injury 1

    Science.gov (United States)

    Iswari, S.; Palta, Jiwan P.

    1989-01-01

    Plasma membrane ATPase has been proposed as a site of functional alteration during early stages of freezing injury. To test this, plasma membrane was purified from Solanum leaflets by a single step partitioning of microsomes in a dextran-polyethylene glycol two phase system. Addition of lysolecithin in the ATPase assay produced up to 10-fold increase in ATPase activity. ATPase activity was specific for ATP with a Km around 0.4 millimolar. Presence of the ATPase enzyme was identified by immunoblotting with oat ATPase antibodies. Using the phase partitioning method, plasma membrane was isolated from Solanum commersonii leaflets which had four different degrees of freezing damage, namely, slight (reversible), partial (partially reversible), substantial and total (irreversible). With slight (reversible) damage the plasma membrane ATPase specific activity increased 1.5- to 2-fold and its Km was decreased by about 3-fold, whereas the specific activity of cytochrome c reductase and cytochrome c oxidase in the microsomes were not different from the control. However, with substantial (lethal, irreversible) damage, there was a loss of membrane protein, decrease in plasma membrane ATPase specific activity and decrease in Km, while cytochrome c oxidase and cytochrome c reductase were unaffected. These results support the hypothesis that plasma membrane ATPase is altered by slight freeze-thaw stress. Images Figure 1 Figure 2 PMID:16666856

  19. Natural Plant Alkaloid (Emetine Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity

    Directory of Open Access Journals (Sweden)

    Ana Luiza Chaves Valadão

    2015-06-01

    Full Text Available Ipecac alkaloids are secondary metabolites produced in the medicinal plant Psychotria ipecacuanha. Emetine is the main alkaloid of ipecac and one of the active compounds in syrup of Ipecac with emetic property. Here we evaluated emetine’s potential as an antiviral agent against Human Immunodeficiency Virus. We performed in vitro Reverse Transcriptase (RT Assay and Natural Endogenous Reverse Transcriptase Activity Assay (NERT to evaluate HIV RT inhibition. Emetine molecular docking on HIV-1 RT was also analyzed. Phenotypic assays were performed in non-lymphocytic and in Peripheral Blood Mononuclear Cells (PBMC with HIV-1 wild-type and HIV-harboring RT-resistant mutation to Nucleoside Reverse Transcriptase Inhibitors (M184V. Our results showed that HIV-1 RT was blocked in the presence of emetine in both models: in vitro reactions with isolated HIV-1 RT and intravirion, measured by NERT. Emetine revealed a strong potential of inhibiting HIV-1 replication in both cellular models, reaching 80% of reduction in HIV-1 infection, with low cytotoxic effect. Emetine also blocked HIV-1 infection of RT M184V mutant. These results suggest that emetine is able to penetrate in intact HIV particles, and bind and block reverse transcription reaction, suggesting that it can be used as anti-HIV microbicide. Taken together, our findings provide additional pharmacological information on the potential therapeutic effects of emetine.

  20. Patient reported activities after reverse total shoulder arthroplasty in rotator cuff arthropathy patients.

    Science.gov (United States)

    Alcobía-Díaz, B; Lópiz, Y; García-Fernández, C; Rizo de Álvaro, B; Marco, F

    Reverse total shoulder arthroplasty in rotator cuff arthropathy patients, improves anteversion and abduction, but not rotational, outcomes. The main aim of this study is to determine its repercussions on daily life activities in our patients. Between 2009 and 2011 we implanted 210 shoulder arthroplasties, 126 of them were reverse total shoulder arthroplasty in a rotator cuff arthropathy context. About 88% were women, with a mean age at time of surgery of 81 years, 95% were retired. The mean follow up was 53 months. The Constant scale, Visual Analogue Scale, Charlson Comorbidity Index, range of motion were measured for each patient and whether they could manage 40 daily life activities by means of a new questionnaire, classifying them according toshoulder functional demand. Mean normalized by sex and age Constant value was 81.2%. Mean Visual Analogue Scale and Charlson Index were 3.56 and 1.69 respectively. Improvement in anteversion and abduction, not in rotational range of motion. Limitation was found in low and high functional demand activities in 20% and 51% respectively, especially those which involved internal rotation. Reverse total shoulder arthroplasty treatment for RCA in the elderly, achieves adequate pain management and good functional outcomes. Nevertheless, an important risk of DLA limitation must be accepted in those which involve internal rotation or shoulder high functional demand. Copyright © 2017 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Age-related similarities and differences in brain activity underlying reversal learning

    Directory of Open Access Journals (Sweden)

    Kaoru eNashiro

    2013-05-01

    Full Text Available The ability to update associative memory is an important aspect of episodic memory and a critical skill for social adaptation. Previous research with younger adults suggests that emotional arousal alters brain mechanisms underlying memory updating; however, it is unclear whether this applies to older adults. Given that the ability to update associative information declines with age, it is important to understand how emotion modulates the brain processes underlying memory updating in older adults. The current study investigated this question using reversal learning tasks, where younger and older participants (age ranges 19-35 and 61-78 respectively learn a stimulus–outcome association and then update their response when contingencies change. We found that younger and older adults showed similar patterns of activation in the frontopolar OFC and the amygdala during emotional reversal learning. In contrast, when reversal learning did not involve emotion, older adults showed greater parietal cortex activity than did younger adults. Thus, younger and older adults show more similarities in brain activity during memory updating involving emotional stimuli than during memory updating not involving emotional stimuli.

  2. Collective ratchet effects and reversals for active matter particles on quasi-one-dimensional asymmetric substrates.

    Science.gov (United States)

    McDermott, Danielle; Olson Reichhardt, Cynthia J; Reichhardt, Charles

    2016-10-19

    Using computer simulations, we study a two-dimensional system of sterically interacting self-mobile run-and-tumble disk-shaped particles with an underlying periodic quasi-one-dimensional asymmetric substrate, and show that a rich variety of collective active ratchet behaviors arise as a function of particle density, activity, substrate period, and the maximum force exerted by the substrate. The net dc drift, or ratchet transport flux, is nonmonotonic since it increases with increased activity but is diminished by the onset of self-clustering of the active particles. Increasing the particle density decreases the ratchet transport flux for shallow substrates but increases the ratchet transport flux for deep substrates due to collective hopping events. At the highest particle densities, the ratchet motion is destroyed by a self-jamming effect. We show that it is possible to realize reversals of the direction of the net dc drift in the deep substrate limit when multiple rows of active particles can be confined in each substrate minimum, permitting emergent particle-like excitations to appear that experience an inverted effective substrate potential. We map out a phase diagram of the forward and reverse ratchet effects as a function of the particle density, activity, and substrate properties.

  3. Steam-cooking rapidly destroys and reverses onion-induced antiplatelet activity

    Directory of Open Access Journals (Sweden)

    Hansen Emilie A

    2012-09-01

    Full Text Available Abstract Background Foods in the diet that can aid in the prevention of diseases are of major interest. Onions are key ingredients in many cuisines around the world and moreover, onion demand has trended higher over the past three decades. An important pharmacological aspect of onion is the ability to inhibit platelet aggregation. Raw onions inhibit platelet aggregation; however, when onions are boiled or heated, antiplatelet activity may be abolished. Methods Onion quarters were steamed for 0, 1, 3, 6, 10, and 15 min. The in vitro antiplatelet activity of a yellow hybrid storage onion was examined at these times on the blood of 12 human subjects using in vitro whole blood aggregometry. Results Contrary to findings reported for boiling, antiplatelet activity was destroyed between 3 and 6 min of steaming, and at 10 min of steaming, cooked onions stimulated platelet activity. Extracts from cooked onion had the potential to reverse the inhibitory effect on blood platelets by 25%. Responses were consistent across all donors. Total polyphenolic concentration and soluble solids were not affected by steaming time. Conclusions The potential value of cooked onion preparations may result in destruction or reversal of antiplatelet activity, without affecting the polyphenolic concentration.

  4. Inhibitory effect of ebselen on cerebral acetylcholinesterase activity in vitro: kinetics and reversibility of inhibition.

    Science.gov (United States)

    Martini, Franciele; Bruning, César Augusto; Soares, Suelen Mendonca; Nogueira, Cristina Wayne; Zeni, Gilson

    2015-01-01

    Ebselen is a synthetic organoselenium compound that has been considered a potential pharmacological agent with low toxicity, showing antioxidant, anti-inflammatory and neuroprotective effects. It is bioavailable, blood-brain barrier permeant and safe based on cellular toxicity and Phase I-III clinical trials. There is evidence that ebselen inhibits acetylcholinesterase (AChE) activity, an enzyme that plays a key role in the cholinergic system by hydrolyzing acetylcholine (ACh), in vitro and ex vivo. This system has a well-known relationship with cognitive process, and AChE inhibitors, such as donepezil and galantamine, have been used to treat cognitive deficits, mainly in the Alzheimer's Disease (AD). However, these drugs have poor bioavailability and a number of side effects, including gastrointestinal upsets and hepatotoxicity. In this way, this study aimed to evaluate the effect of ebselen on cerebral AChE activity in vitro and to determine the kinetic profile and the reversibility of inhibition by dialysis. Ebselen inhibited the cerebral AChE activity with an IC50 of 29 µM, similar to IC50 found with pure AChE from electric eel, demonstrating a mixed and reversible inhibition of AChE, since it increased Km and decreased Vmax. The AChE activity was recovered within 60 min of dialysis. Therefore, the use of ebselen as a therapeutic agent for treatment of AD should be considered, although memory behavior tasks are needed to support such hypothesis.

  5. A functional polymorphism in the prodynorphin gene affects cognitive flexibility and brain activation during reversal learning.

    Directory of Open Access Journals (Sweden)

    Mikhail eVotinov

    2015-07-01

    Full Text Available Whether the opioid system plays a role in the ability to flexibly adapt behavior is still unclear. We used fMRI to investigate the effect of a nucleotide tandem repeat (68-bp VNTR functional polymorphism of the prodynorphin gene on cerebral activation during a reversal learning task in which participants had to flexibly adapt stimulus-response associations. Past studies suggested that alleles with 3 or 4 repeats (HH genotype of this polymorphism are associated with higher levels of dynorphin peptides than alleles with 1 or 2 repeats (LL genotype. On the behavioral level, the HH group made more perseverative errors than the LL group. On the neural level, the HH group demonstrated less engagement of left orbitofrontal cortex (lOFC and cortico-striatal circuitry, and lower effective connectivity of lOFC with anterior midcingulate cortex and anterior insula/ventrolateral prefrontal cortex during reversal learning and processing negative feedback. This points to a lower ability of the HH genotype to monitor or adapt to changes in reward contingencies. These findings provide first evidence that dynorphins may contribute to individual differences in reversal learning, and that considering the opioid system may shed new light on the neurochemical correlates of decision-making and behavioral regulation.

  6. Antitumor Activity and Mechanism of a Reverse Transcriptase Inhibitor, Dapivirine, in Glioblastoma

    OpenAIRE

    Liu, Weiwen; Song, Xian-lu; Zhao, Shan-chao; He, Minyi; Wang, Hai; Chen, Ziyang; Xiang, Wei; Yi, Guozhong; Qi, Songtao; Liu, Yawei

    2018-01-01

    Ethnopharmacological relevance: Dapivirine is one of reverse transcriptase inhibitors (RTIs). It is the prototype of diarylpyrimidines (DAPY), formerly known as TMC120 or DAPY R147681 (IUPAC name: 4- [[4-(2, 4, 6-trimethylphenyl) amino]-2-pyrimidinyl] amino]-benzonitrile; CAS no.244767-67-7). Aim: The purpose of this study is to investigate the antitumor activity of dapivirine, one of the RTIs, on U87 glioblastoma (GBM) cells in vitro and in vivo. Materials and Methods: U87 GBM cells were cul...

  7. Numerical studies of active current profile control in the reversed-field pinch

    International Nuclear Information System (INIS)

    Dahlin, J-E; Scheffel, J; Anderson, J K

    2007-01-01

    Quenching of the reversed-field pinch (RFP) dynamo is observed in numerical simulations using current profile control. A novel algorithm employing active feedback of the dynamo field has been utilized. The quasi-steady state achieved represents an important improvement as compared with earlier numerical work and may indicate a direction for the design of future experiments. Both earlier and the novel schemes of feedback control result in quasi-single helicity states. The energy confinement time and poloidal beta are observed to be substantially increased, as compared with the conventional RFP, in both the cases. Different techniques for experimental implementation are discussed

  8. [Reversibility of the leukocyte activation state studied in a model of endogenous pyrogen formation by granulocytes].

    Science.gov (United States)

    Rybakina, E G; Sorokin, A V

    1980-08-01

    The pyrogen-releasing capacity of rabbit exudate granulocytes can be temporarily suppressed during incubation in the whole plasma and then recovered during cell transfer into 0.15 M NaCl or stimulation with the bacterial lipopolysaccharide, pyrogenal. The inhibitors of protein synthesis added to the granulocytes when they are being transferred from plasma to 0.15 M NaCl do not suppress the pyrogen release. The inhibitory action of the whole plasma on the pyrogen release is due to the presence in it of potassium and calcium ions. The inhibitory factors of plasma reversibly suppress the pyrogen release but do not eliminate the leukocyte activation.

  9. Pituitary Adenylate Cyclase-Activating Polypeptide Reverses Ammonium Metavanadate-Induced Airway Hyperresponsiveness in Rats

    Directory of Open Access Journals (Sweden)

    Mounira Tlili

    2015-01-01

    Full Text Available The rate of atmospheric vanadium is constantly increasing due to fossil fuel combustion. This environmental pollution favours vanadium exposure in particular to its vanadate form, causing occupational bronchial asthma and bronchitis. Based on the well admitted bronchodilator properties of the pituitary adenylate cyclase-activating polypeptide (PACAP, we investigated the ability of this neuropeptide to reverse the vanadate-induced airway hyperresponsiveness in rats. Exposure to ammonium metavanadate aerosols (5 mg/m3/h for 15 minutes induced 4 hours later an array of pathophysiological events, including increase of bronchial resistance and histological alterations, activation of proinflammatory alveolar macrophages, and increased oxidative stress status. Powerfully, PACAP inhalation (0.1 mM for 10 minutes alleviated many of these deleterious effects as demonstrated by a decrease of bronchial resistance and histological restoration. PACAP reduced the level of expression of mRNA encoding inflammatory chemokines (MIP-1α, MIP-2, and KC and cytokines (IL-1α and TNF-α in alveolar macrophages and improved the antioxidant status. PACAP reverses the vanadate-induced airway hyperresponsiveness not only through its bronchodilator activity but also by counteracting the proinflammatory and prooxidative effects of the metal. Then, the development of stable analogs of PACAP could represent a promising therapeutic alternative for the treatment of inflammatory respiratory disorders.

  10. Differential Regulation of Telomerase Reverse Transcriptase Promoter Activation and Protein Degradation by Histone Deacetylase Inhibition.

    Science.gov (United States)

    Qing, Hua; Aono, Jun; Findeisen, Hannes M; Jones, Karrie L; Heywood, Elizabeth B; Bruemmer, Dennis

    2016-06-01

    Telomerase reverse transcriptase (TERT) maintains telomeres and is rate limiting for replicative life span. While most somatic tissues silence TERT transcription resulting in telomere shortening, cells derived from cancer or cardiovascular diseases express TERT and activate telomerase. In the present study, we demonstrate that histone deacetylase (HDAC) inhibition induces TERT transcription and promoter activation. At the protein level in contrast, HDAC inhibition decreases TERT protein abundance through enhanced degradation, which decreases telomerase activity and induces senescence. Finally, we demonstrate that HDAC inhibition decreases TERT expression during vascular remodeling in vivo. These data illustrate a differential regulation of TERT transcription and protein stability by HDAC inhibition and suggest that TERT may constitute an important target for the anti-proliferative efficacy of HDAC inhibitors. © 2015 Wiley Periodicals, Inc.

  11. The reverse transcription inhibitor abacavir shows anticancer activity in prostate cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Francesca Carlini

    Full Text Available BACKGROUND: Transposable Elements (TEs comprise nearly 45% of the entire genome and are part of sophisticated regulatory network systems that control developmental processes in normal and pathological conditions. The retroviral/retrotransposon gene machinery consists mainly of Long Interspersed Nuclear Elements (LINEs-1 and Human Endogenous Retroviruses (HERVs that code for their own endogenous reverse transcriptase (RT. Interestingly, RT is typically expressed at high levels in cancer cells. Recent studies report that RT inhibition by non-nucleoside reverse transcriptase inhibitors (NNRTIs induces growth arrest and cell differentiation in vitro and antagonizes growth of human tumors in animal model. In the present study we analyze the anticancer activity of Abacavir (ABC, a nucleoside reverse transcription inhibitor (NRTI, on PC3 and LNCaP prostate cancer cell lines. PRINCIPAL FINDINGS: ABC significantly reduces cell growth, migration and invasion processes, considerably slows S phase progression, induces senescence and cell death in prostate cancer cells. Consistent with these observations, microarray analysis on PC3 cells shows that ABC induces specific and dose-dependent changes in gene expression, involving multiple cellular pathways. Notably, by quantitative Real-Time PCR we found that LINE-1 ORF1 and ORF2 mRNA levels were significantly up-regulated by ABC treatment. CONCLUSIONS: Our results demonstrate the potential of ABC as anticancer agent able to induce antiproliferative activity and trigger senescence in prostate cancer cells. Noteworthy, we show that ABC elicits up-regulation of LINE-1 expression, suggesting the involvement of these elements in the observed cellular modifications.

  12. Synthesis, Antiproliferative, and Multidrug Resistance Reversal Activities of Heterocyclic α,β-Unsaturated Carbonyl Compounds.

    Science.gov (United States)

    Sun, Ju-Feng; Hou, Gui-Ge; Zhao, Feng; Cong, Wei; Li, Hong-Juan; Liu, Wen-Shuai; Wang, Chunhua

    2016-10-01

    A series of heterocyclic α,β-unsaturated carbonyl compounds (1a-1d, 2a-2d, 3a-3d, 4a-3d, and 5a-5d) with 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore were synthesized for the development of anticancer and multidrug resistance reverting agents. The antiproliferative activities were tested against nine human cancer cell lines. Approximately 73% of the IC50 values were below 5 μm, while 35% of these figures were submicromolar, and compounds 3a-3d with 4-trifluoro methyl in the arylidene benzene rings were the most potent, since their IC50 values are between 0.06 and 3.09 μm against all cancer cell lines employed. Meanwhile, their multidrug resistance reversal properties and cellular uptake were further examined. The data displayed that all of these compounds could reverse multidrug resistance, particularly, compounds 3a and 4a demonstrated both potent multidrug resistance reverting properties and strong antiproliferative activities, which can be taken as leading molecules for further research of dual effect agents in tumor chemotherapy. © 2016 John Wiley & Sons A/S.

  13. Targeted HIV-1 Latency Reversal Using CRISPR/Cas9-Derived Transcriptional Activator Systems.

    Directory of Open Access Journals (Sweden)

    Julia K Bialek

    Full Text Available CRISPR/Cas9 technology is currently considered the most advanced tool for targeted genome engineering. Its sequence-dependent specificity has been explored for locus-directed transcriptional modulation. Such modulation, in particular transcriptional activation, has been proposed as key approach to overcome silencing of dormant HIV provirus in latently infected cellular reservoirs. Currently available agents for provirus activation, so-called latency reversing agents (LRAs, act indirectly through cellular pathways to induce viral transcription. However, their clinical performance remains suboptimal, possibly because reservoirs have diverse cellular identities and/or proviral DNA is intractable to the induced pathways. We have explored two CRISPR/Cas9-derived activator systems as targeted approaches to induce dormant HIV-1 proviral DNA. These systems recruit multiple transcriptional activation domains to the HIV 5' long terminal repeat (LTR, for which we have identified an optimal target region within the LTR U3 sequence. Using this target region, we demonstrate transcriptional activation of proviral genomes via the synergistic activation mediator complex in various in culture model systems for HIV latency. Observed levels of induction are comparable or indeed higher than treatment with established LRAs. Importantly, activation is complete, leading to production of infective viral particles. Our data demonstrate that CRISPR/Cas9-derived technologies can be applied to counteract HIV latency and may therefore represent promising novel approaches in the quest for HIV elimination.

  14. Nanoconfinement in activated mesoporous carbon of calcium borohydride for improved reversible hydrogen storage.

    Science.gov (United States)

    Comănescu, Cezar; Capurso, Giovanni; Maddalena, Amedeo

    2012-09-28

    Mesoporous carbon frameworks were synthesized using the soft-template method. Ca(BH(4))(2) was incorporated into activated mesoporous carbon by the incipient wetness method. The activation of mesoporous carbon was necessary to optimize the surface area and pore size. Thermal programmed absorption measurements showed that the confinement of this borohydride into carbon nanoscaffolds improved its reversible capacity (relative to the reactive portion) and performance of hydrogen storage compared to unsupported borohydride. Hydrogen release from the supported hydride started at a temperature as low as 100 °C and the dehydrogenation rate was fast compared to the bulk borohydride. In addition, the hydrogen pressure necessary to regenerate the borohydride from the dehydrogenation products was reduced.

  15. Menin-MLL inhibitors reverse oncogenic activity of MLL fusion proteins in leukemia.

    Science.gov (United States)

    Grembecka, Jolanta; He, Shihan; Shi, Aibin; Purohit, Trupta; Muntean, Andrew G; Sorenson, Roderick J; Showalter, Hollis D; Murai, Marcelo J; Belcher, Amalia M; Hartley, Thomas; Hess, Jay L; Cierpicki, Tomasz

    2012-01-29

    Translocations involving the mixed lineage leukemia (MLL) gene result in human acute leukemias with very poor prognosis. The leukemogenic activity of MLL fusion proteins is critically dependent on their direct interaction with menin, a product of the multiple endocrine neoplasia (MEN1) gene. Here we present what are to our knowledge the first small-molecule inhibitors of the menin-MLL fusion protein interaction that specifically bind menin with nanomolar affinities. These compounds effectively reverse MLL fusion protein-mediated leukemic transformation by downregulating the expression of target genes required for MLL fusion protein oncogenic activity. They also selectively block proliferation and induce both apoptosis and differentiation of leukemia cells harboring MLL translocations. Identification of these compounds provides a new tool for better understanding MLL-mediated leukemogenesis and represents a new approach for studying the role of menin as an oncogenic cofactor of MLL fusion proteins. Our findings also highlight a new therapeutic strategy for aggressive leukemias with MLL rearrangements.

  16. A reverse pathway? Actual and perceived skill proficiency and physical activity.

    Science.gov (United States)

    Barnett, Lisa M; Morgan, Philip J; Van Beurden, Eric; Ball, Kylie; Lubans, David R

    2011-05-01

    Motor skills are considered a prerequisite to physical activity, yet the relationship may be reciprocal and perceived sports competence might mediate associations. In 2006/2007, 215 adolescents completed motor skill proficiency (Get Skilled Get Active), perceived sport competence (Physical Self-Perception Profile) and physical activity assessments (Adolescent Physical Activity Recall Questionnaire) as part of the Physical Activity and Skills Study. Using AMOS (Version 7.0), reciprocal relationships were examined between motor skill (object control and locomotor) and moderate to vigorous physical activity (MVPA). Both models were then run in different versions to understand the role of perceived sports competence as a potential mediator. Mean age was 16.4 yr (SD=0.6), 51.6% (111/215) were females. A reciprocal relationship between object control and MVPA and a one-way relationship from MVPA to locomotor skill was found. When perceived sports competence was examined as a mediator, the best-fitting model versions explained 16% (R=0.16) MVPA variation, and 30% object control (R=0.30), and 12% locomotor skill variation (R=0.12) (reverse relationship). Perceived sports competence partially mediates the relationship between object control proficiency and physical activity for both directions and fully mediates the relationship between physical activity and locomotor skill; but only when locomotor skill is the outcome. If the relationship between object control skill and physical activity is viewed as a "positive feedback loop," skill development and increasing physical activity should simultaneously be targeted in physical activity interventions. Increasing perceived sport competence should also be an intervention focus. © 2011 by the American College of Sports Medicine

  17. Purification of reversibly oxidized proteins (PROP reveals a redox switch controlling p38 MAP kinase activity.

    Directory of Open Access Journals (Sweden)

    Dennis J Templeton

    2010-11-01

    Full Text Available Oxidation of cysteine residues of proteins is emerging as an important means of regulation of signal transduction, particularly of protein kinase function. Tools to detect and quantify cysteine oxidation of proteins have been a limiting factor in understanding the role of cysteine oxidation in signal transduction. As an example, the p38 MAP kinase is activated by several stress-related stimuli that are often accompanied by in vitro generation of hydrogen peroxide. We noted that hydrogen peroxide inhibited p38 activity despite paradoxically increasing the activating phosphorylation of p38. To address the possibility that cysteine oxidation may provide a negative regulatory effect on p38 activity, we developed a biochemical assay to detect reversible cysteine oxidation in intact cells. This procedure, PROP, demonstrated in vivo oxidation of p38 in response to hydrogen peroxide and also to the natural inflammatory lipid prostaglandin J2. Mutagenesis of the potential target cysteines showed that oxidation occurred preferentially on residues near the surface of the p38 molecule. Cysteine oxidation thus controls a functional redox switch regulating the intensity or duration of p38 activity that would not be revealed by immunodetection of phosphoprotein commonly interpreted as reflective of p38 activity.

  18. Dual fluorescent molecular substrates selectively report the activation, sustainability and reversibility of cellular PKB/Akt activity.

    Science.gov (United States)

    Shen, Duanwen; Bai, Mingfeng; Tang, Rui; Xu, Baogang; Ju, Xiaoming; Pestell, Richard G; Achilefu, Samuel

    2013-01-01

    Using a newly developed near-infrared (NIR) dye that fluoresces at two different wavelengths (dichromic fluorescence, DCF), we discovered a new fluorescent substrate for Akt, also known as protein kinase B, and a method to quantitatively report this enzyme's activity in real time. Upon insulin activation of cellular Akt, the enzyme multi-phosphorylated a single serine residue of a diserine DCF substrate in a time-dependent manner, culminating in monophospho- to triphospho-serine products. The NIR DCF probe was highly selective for the Akt1 isoform, which was demonstrated using Akt1 knockout cells derived from MMTV-ErbB2 transgenic mice. The DCF mechanism provides unparalleled potential to assess the stimulation, sustainability, and reversibility of Akt activation longitudinally. Importantly, NIR fluorescence provides a pathway to translate findings from cells to living organisms, a condition that could eventually facilitate the use of these probes in humans.

  19. Cigarette smoking and schizophrenia independently and reversibly altered intrinsic brain activity.

    Science.gov (United States)

    Liu, Huan; Luo, Qi; Du, Wanyi; Li, Xingbao; Zhang, Zhiwei; Yu, Renqiang; Chen, Xiaolu; Meng, Huaqing; Du, Lian

    2018-01-03

    Schizophrenia patients are at high risk for cigarette smoking, but the neurobiological mechanisms of this comorbid association are relatively unknown. Long-term nicotine intake may impact brain that are independently and additively associated with schizophrenia. We investigated whether altered intrinsic brain activity (iBA) related to schizophrenia pathology is also associated with nicotine addiction. Forty-two schizophrenia patients (21 smokers and 21 nonsmokers) and 21 sex- and age-matched healthy nonsmokers underwent task-free functional MRI. Whole brain iBA was measured by the amplitude of spontaneous low frequency fluctuation. Furthermore, correlation analyses between iBA, symptom severity and nicotine addiction severity were performed. We found that prefrontal cortex, right caudate, and right postcentral gyrus were related to both disease and nicotine addiction effects. More importantly, schizophrenia smokers, compared to schizophrenia nonsmokers showed reversed iBA in the above brain regions. In addition, schizophrenia smokers, relative to nonsmokers, altered iBA in the left striatal and motor cortices. The iBA of the right caudate was negatively correlated with symptom severity. The iBA of the right postcentral gyrus negatively correlated with nicotine addiction severity. The striatal and motor cortices could potentially increase the vulnerability of smoking in schizophrenia. More importantly, smoking reversed iBA in the right striatal and prefrontal cortices, consistent with the self-medication theory in schizophrenia. Smoking altered left striatal and motor cortices activity, suggesting that the nicotine addiction effect was independent of disease. These results provide a local property of intrinsic brain activity mechanism that contributes to cigarette smoking and schizophrenia.

  20. Blanket activation and afterheat for the Compact Reversed-Field Pinch Reactor

    International Nuclear Information System (INIS)

    Davidson, J.W.; Battat, M.E.

    1985-01-01

    A detailed assessment has been made of the activation and afterheat for a Compact Reversed-Field Pinch Reactor (CRFPR) blanket using a two-dimensional model that included the limiter, the vacuum ducts, and the manifolds and headers for cooling the limiter and the first and second walls. Region-averaged, multigroup fluxes and prompt gamma-ray/neutron heating rates were calculated using the two-dimensional, discrete-ordinates code TRISM. Activation and depletion calculations were performed with the code FORIG using one-group cross sections generated with the TRISM region-averaged fluxes. Afterheat calculations were performed for regions near the plasma, i.e., the limiter, first wall, etc. assuming a 10-day irradiation. Decay heats were computed for decay periods up to 100 minutes. For the activation calculations, the irradiation period was taken to be one year and blanket activity inventories were computed for decay times to 4 x 10 5 years. These activities were also calculated as the toxicity-weighted biological hazard potential (BHP). 15 refs

  1. Cytotoxic and multidrug resistance reversal activity of a vegetable, 'Anastasia Red', a variety of sweet pepper.

    Science.gov (United States)

    Motohashi, Noboru; Wakabayashi, Hidetsugu; Kurihara, Teruo; Takada, Yuko; Maruyama, Shichiro; Sakagami, Hiroshi; Nakashima, Hideki; Tani, Satoru; Shirataki, Yoshiaki; Kawase, Masami; Wolfard, Kristina; Molnár, Joseph

    2003-04-01

    The vegetable, Anastasia Red, Capsicum annuum L. var. angulosum Mill. (Solanaceae) was successively extracted with hexane, acetone, methanol and 70% methanol, and the extracts were further separated into a total of 21 fractions by silica gel or octadecylsilane (ODS) column chromatography. The biological activities of extracts and fractions were determined. These extracts showed relatively higher cytotoxic activity against two human oral tumor cell lines (HSC-2, HSG) than against normal human gingival fibroblasts (HGF), suggesting a tumor-specific cytotoxic activity. The cytotoxic activity of these extracts was enhanced by fractionation on silica gel [H2, A2, M1-M3] or ODS column chromatography [70M]. Several fractions [H2, H4, H5, A1, A2, A3, A5, A6, A7, M2] reversed the multidrug resistance (MDR) phenotype with L5178 mouse lymphoma T cells, more efficiently than (+/-)-verapamil. The extracts and fractions did not show any detectable anti-human immunodeficiency virus (HIV) or anti-Helicobacter pylori activity. Thus, this study suggests the effective and selective antitumor potential of 'Anastasia Red' of sweet pepper for further phytochemical and biological investigation. Copyright 2003 John Wiley & Sons, Ltd.

  2. Telomerase Activation in Atherosclerosis and Induction of Telomerase Reverse Transcriptase Expression by Inflammatory Stimuli in Macrophages

    Science.gov (United States)

    Gizard, Florence; Heywood, Elizabeth B.; Findeisen, Hannes M.; Zhao, Yue; Jones, Karrie L.; Cudejko, Cèline; Post, Ginell R.; Staels, Bart; Bruemmer, Dennis

    2010-01-01

    Objective Telomerase serves as a critical regulator of tissue renewal. Although telomerase activity is inducible in response to various environmental cues, it remains unknown whether telomerase is activated during the inflammatory remodeling underlying atherosclerosis formation. To address this question, we investigated in the present study the regulation of telomerase in macrophages and during atherosclerosis development in LDL-receptor-deficient mice. Methods and Results We demonstrate that inflammatory stimuli activate telomerase in macrophages by inducing the expression of the catalytic subunit telomerase reverse transcriptase (TERT). Reporter and chromatin immunoprecipitation assays identified a previously unrecognized NF-κB response element in the TERT promoter, to which NF-κB is recruited during inflammation. Inhibition of NF-κB signaling completely abolished the induction of TERT expression, characterizing TERT as a bona fide NF-κB target gene. Furthermore, functional experiments revealed that TERT-deficiency results in a senescent cell phenotype. Finally, we demonstrate high levels of TERT expression in macrophages of human atherosclerotic lesions and establish that telomerase is activated during atherosclerosis development in LDL-receptor-deficient mice. Conclusion These results characterize TERT as a previously unrecognized NF-κB target gene in macrophages and demonstrate that telomerase is activated during atherosclerosis. This induction of TERT expression prevents macrophage senescence and may have important implications for the development of atherosclerosis. PMID:21106948

  3. Wave-front reversal in a copper-vapor active medium

    Energy Technology Data Exchange (ETDEWEB)

    Bunkin, F.V.; Savranskii, V.V.; Shafeev, G.A.

    1981-09-01

    The implementation of wave-front reversal in a copper-vapor laser resonator is reported. The frequencies of the signal wave and the reversed wave are the same, and the dependence of reversed-signal power on input-signal power has a threshold character. Photographs of the reconstructed object image upon insertion of a distorting phase plate into the resonator are presented.

  4. Determination of trace elements in acid rain by reversed phase extraction chromatography and neutron activation

    International Nuclear Information System (INIS)

    Rao, R.R.; Goski, D.G.; Chatt, A.

    1991-01-01

    A preconcentration neutron activation analysis (PNAA) method has been developed for the simultaneous determination of selected trace elements in acid rain and other water samples. The method consists of preconcentration of the elements by reversed phase extraction chromatography using oxine-loaded Amberlite XAD-2 resin. Nearly 100% recoveries were obtained for Co, Cu, Hg, V and Zn at pH 6.0 and for Cd at pH 7.0. Manganese gave incomplete recoveries at the pH range of 4.0-8.0 studies. Various factors that can influence preconcentration of the elements have been investigated in detail. The precision and accuracy of measurements have been evaluated by analyzing certified reference materials. The detection limits have been found to be of the order of ppb. The PNAA method has been applied to a number of acid rain and other water samples

  5. Re-activation of degraded nickel cermet anodes - Nano-particle formation via reverse current pulses

    Science.gov (United States)

    Hauch, A.; Marchese, M.; Lanzini, A.; Graves, C.

    2018-02-01

    The Ni/yttria-stabilized-zirconia (YSZ) cermet is the most commonly applied fuel electrode for solid oxide cells (SOCs). Loss of Ni/YSZ electrode activity is a key life-time limiting factor of the SOC. Developing means to mitigate this loss of performance or re-activate a fuel electrode is therefore important. In this work, we report a series of five tests on state-of-the-art Ni/YSZ-YSZ-CGObarrier-LSC/CGO cells. All cells were deliberately degraded via gas stream impurities in CO2/CO or harsh steam electrolysis operation. The cells were re-activated via a variety of reverse current treatments (RCTs). Via electrochemical impedance spectroscopy, we found that the Ni/YSZ electrode performance could be recovered via RCT, but not via constant fuel cell operation. For optimized RCT, we obtained a lower Ni/YSZ electrode resistance than the initial resistance. E.g. at 700 °C we measured fuel electrode resistance of 180 mΩ cm2, 390 mΩ cm2, and 159 mΩ cm2 before degradation, after degradation and after re-activation via RCT, respectively. Post-test SEM revealed that the RCT led to formation of nano-particles in the fuel electrode. Besides the remarkable improvement, the results also showed that RCTs can weaken Ni/YSZ interfaces and the electrode/electrolyte interface. This indicates that finding an optimum RCT profile is crucial for achieving maximum benefit.

  6. Subsurface structures of the active reverse fault zones in Japan inferred from gravity anomalies.

    Science.gov (United States)

    Matsumoto, N.; Sawada, A.; Hiramatsu, Y.; Okada, S.; Tanaka, T.; Honda, R.

    2016-12-01

    The object of our study is to examine subsurface features such as continuity, segmentation and faulting type, of the active reverse fault zones. We use the gravity data published by the Gravity Research Group in Southwest Japan (2001), the Geographical Survey Institute (2006), Yamamoto et al. (2011), Honda et al. (2012), and the Geological Survey of Japan, AIST (2013) in this study. We obtained the Bouguer anomalies through terrain corrections with 10 m DEM (Sawada et al. 2015) under the assumed density of 2670 kg/m3, a band-pass filtering, and removal of linear trend. Several derivatives and structural parameters calculated from a gravity gradient tensor are applied to highlight the features, such as a first horizontal derivatives (HD), a first vertical derivatives (VD), a normalized total horizontal derivative (TDX), a dip angle (β), and a dimensionality index (Di). We analyzed 43 reverse fault zones in northeast Japan and the northern part of southwest Japan among major active fault zones selected by Headquarters for Earthquake Research Promotion. As the results, the subsurface structural boundaries clearly appear along the faults at 21 faults zones. The weak correlations appear at 13 fault zones, and no correlations are recognized at 9 fault zones. For example, in the Itoigawa-Shizuoka tectonic line, the subsurface structure boundary seems to extend further north than the surface trace. Also, a left stepping structure of the fault around Hakuba is more clearly observed with HD. The subsurface structures, which detected as the higher values of HD, are distributed on the east side of the surface rupture in the north segments and on the west side in the south segments, indicating a change of the dip direction, the east dipping to the west dipping, from north to south. In the Yokote basin fault zone, the subsurface structural boundary are clearly detected with HD, VD and TDX along the fault zone in the north segment, but less clearly in the south segment. Also, Di

  7. N2O decomposition over Fe/ZSM-5: reversible generation of highly active cationic Fe species

    NARCIS (Netherlands)

    Zhu, Q.; Hensen, E.J.M.; Mojet, B.L.; Wolput, van J.H.M.C.; Santen, van R.A.

    2002-01-01

    Fe-oxide species in Fe/ZSM-5 (prepared by chemical vapor deposition of FeCl3)-active in N2O decomposition-react with zeolite protons during high temperature calcination to give highly active cationic Fe species, this transformation being reversible upon exposure to water vapor at lower temperature

  8. [Temporary disappearance of EEG activity during reversible respiratory failure in rabbits and cats].

    Science.gov (United States)

    Jurco, M; Tomori, Z; Tkácová, R; Calfa, J

    1989-02-01

    The dynamics of changes of EEG activity was studied on the model of reversible respiratory failure in rabbits and cats in pentobarbital anesthesia. During N2 inhalation, apnea of 60 second duration, and subsequent resuscitation the electrocorticogram in bifrontal and bioccipital connection was recorded. Evaluation of 19 episodes of apnea in 7 rabbits and of 25 episodes in 8 cats yielded the following results: 1. During hyperventilation induced by N2 inhalation a certain activation of the EEG was observed (spindles more pronounced, increased occurrence rate of discharges of the reticular activation system). 2. At the onset of apnea the EEG was still distinct, suggesting that primary apnea is presumably not caused by anoxia and the accompanying electric silence of the structures that control respiration. 3. Disappearance of EEG occurred within 50 seconds from the onset of apnea in rabbits and within 30 seconds in cats. 4. After repeated episodes of apnea lasting for 60 sec., artificial ventilation mostly resulted in normalization of EEG.

  9. Reverse translation in tuberculosis: neutrophils as clues for development of active disease

    Directory of Open Access Journals (Sweden)

    Anca eDorhoi

    2014-02-01

    Full Text Available Tuberculosis (TB is a major health issue globally. Although typically the disease can be cured by chemotherapy and prevented – at least in part, in newborn by vaccination, general consensus exists that development of novel intervention measures requires better understanding of disease mechanisms. Human TB is characterized by polarity between host resistance as seen in 2 billion individuals with latent TB infection and susceptibility occurring in 9 million individuals who develop active TB disease every year. Experimental animal models often do not reflect this polarity adequately, calling for a reverse translational approach. Gene expression profiling has allowed identification of biomarkers that discriminate between latent infection and active disease. Functional analysis of most relevant markers in experimental animal models can help to better understand mechanisms driving disease progression. We have embarked on in-depth characterization of candidate markers of pathology and protection hereby harnessing mouse mutants with defined gene deficiencies. Analysis of mutants deficient in miR223 expression and CXCL5 production allowed elucidation of relevant pathogenic mechanisms. Intriguingly, these deficiencies were linked to aberrant neutrophil activities. Our findings point to a detrimental potential of neutrophils in TB. Reciprocally, measures that control neutrophils should be leveraged for amelioration of TB in adjunct to chemotherapy.

  10. Antitumor Activity and Mechanism of a Reverse Transcriptase Inhibitor, Dapivirine, in Glioblastoma.

    Science.gov (United States)

    Liu, Weiwen; Song, Xian-Lu; Zhao, Shan-Chao; He, Minyi; Wang, Hai; Chen, Ziyang; Xiang, Wei; Yi, Guozhong; Qi, Songtao; Liu, Yawei

    2018-01-01

    Dapivirine is one of reverse transcriptase inhibitors (RTIs). It is the prototype of diarylpyrimidines (DAPY), formerly known as TMC120 or DAPY R147681 (IUPAC name: 4- [[4-(2, 4, 6-trimethylphenyl) amino]-2-pyrimidinyl] amino]-benzonitrile; CAS no.244767-67-7). The purpose of this study is to investigate the antitumor activity of dapivirine, one of the RTIs, on U87 glioblastoma (GBM) cells in vitro and in vivo . U87 GBM cells were cultured and treated with or without dapivirine. Cell viability was evaluated by CCK-8 (Cell Counting Kit 8, CCK-8) assay; apoptosis was analyzed by flow cytometry; cell migration was evaluated by Boyden Chamber assay; Western blotting was performed to detect proteins related to apoptosis, epithelial-to-mesenchymal transition and autophagy. PathScan intracellular signaling array kit was used to detect important and well-characterized signaling molecules. Tumor xenograft model in nude mice was used to evaluate the antitumorigenic effect in vivo . Dapivirine weakened proliferation of glioma cells and induced the apoptosis of U87 glioblastoma cells. Furthermore, dapivirine regulated autophagy and induced Akt, Bad and SAPK/JNK activations. Moreover, the inhibition of glioma cell growth by dapivirine was also observed in nude mice in vivo . In summary, in our study dapivirine exposure induces stress, resulting in JNK and PI3K/Akt pathway activation through diminished inhibition of the apoptosis and autophagy cascade in U87 GBM cells, which inhibits cell growth in vitro and in vivo .

  11. Reversal of experimental colitis disease activity in mice following administration of an adenoviral IL-10 vector.

    Science.gov (United States)

    Sasaki, Makoto; Mathis, J Michael; Jennings, Merilyn H; Jordan, Paul; Wang, Yuping; Ando, Tomoaki; Joh, Takashi; Alexander, J Steven

    2005-10-31

    Genetic deficiency in the expression of interleukin-10 (IL-10) is associated with the onset and progression of experimental inflammatory bowel disease (IBD). The clinical significance of IL-10 expression is supported by studies showing that immune-augmentation of IL-10 prevents inflammation and mucosal damage in animal models of colitis and in human colitis. Interleukin-10 (IL-10), an endogenous anti-inflammatory and immunomodulating cytokine, has been shown to prevent some inflammation and injury in animal and clinical studies, but the efficacy of IL-10 treatment remains unsatisfactory. We found that intra-peritoneal administration of adenoviral IL-10 to mice significantly reversed colitis induced by administration of 3% DSS (dextran sulfate), a common model of colitis. Adenoviral IL-10 (Ad-IL10) transfected mice developed high levels of IL-10 (394 +/- 136 pg/ml) within the peritoneal cavity where the adenovirus was expressed. Importantly, when given on day 4 (after the induction of colitis w/DSS), Ad-IL10 significantly reduced disease activity and weight loss and completely prevented histopathologic injury to the colon at day 10. Mechanistically, compared to Ad-null and DSS treated mice, Ad-IL10 and DSS-treated mice were able to suppress the expression of MAdCAM-1, an endothelial adhesion molecule associated with IBD. Our results suggest that Ad-IL10 (adenoviral IL-10) gene therapy of the intestine or peritoneum may be useful in the clinical treatment of IBD, since we demonstrated that this vector can reverse the course of an existing gut inflammation and markers of inflammation.

  12. Reversal of experimental colitis disease activity in mice following administration of an adenoviral IL-10 vector

    Directory of Open Access Journals (Sweden)

    Ando Tomoaki

    2005-10-01

    Full Text Available Abstract Genetic deficiency in the expression of interleukin-10 (IL-10 is associated with the onset and progression of experimental inflammatory bowel disease (IBD. The clinical significance of IL-10 expression is supported by studies showing that immune-augmentation of IL-10 prevents inflammation and mucosal damage in animal models of colitis and in human colitis. Interleukin-10 (IL-10, an endogenous anti-inflammatory and immunomodulating cytokine, has been shown to prevent some inflammation and injury in animal and clinical studies, but the efficacy of IL-10 treatment remains unsatisfactory. We found that intra-peritoneal administration of adenoviral IL-10 to mice significantly reversed colitis induced by administration of 3% DSS (dextran sulfate, a common model of colitis. Adenoviral IL-10 (Ad-IL10 transfected mice developed high levels of IL-10 (394 +/- 136 pg/ml within the peritoneal cavity where the adenovirus was expressed. Importantly, when given on day 4 (after the induction of colitis w/DSS, Ad-IL10 significantly reduced disease activity and weight loss and completely prevented histopathologic injury to the colon at day 10. Mechanistically, compared to Ad-null and DSS treated mice, Ad-IL10 and DSS-treated mice were able to suppress the expression of MAdCAM-1, an endothelial adhesion molecule associated with IBD. Our results suggest that Ad-IL10 (adenoviral IL-10 gene therapy of the intestine or peritoneum may be useful in the clinical treatment of IBD, since we demonstrated that this vector can reverse the course of an existing gut inflammation and markers of inflammation.

  13. Nitrated Fatty Acids Reverse Cigarette Smoke-Induced Alveolar Macrophage Activation and Inhibit Protease Activity via Electrophilic S-Alkylation.

    Science.gov (United States)

    Reddy, Aravind T; Lakshmi, Sowmya P; Muchumarri, Ramamohan R; Reddy, Raju C

    2016-01-01

    Nitrated fatty acids (NFAs), endogenous products of nonenzymatic reactions of NO-derived reactive nitrogen species with unsaturated fatty acids, exhibit substantial anti-inflammatory activities. They are both reversible electrophiles and peroxisome proliferator-activated receptor γ (PPARγ) agonists, but the physiological implications of their electrophilic activity are poorly understood. We tested their effects on inflammatory and emphysema-related biomarkers in alveolar macrophages (AMs) of smoke-exposed mice. NFA (10-nitro-oleic acid or 12-nitrolinoleic acid) treatment downregulated expression and activity of the inflammatory transcription factor NF-κB while upregulating those of PPARγ. It also downregulated production of inflammatory cytokines and chemokines and of the protease cathepsin S (Cat S), a key mediator of emphysematous septal destruction. Cat S downregulation was accompanied by decreased AM elastolytic activity, a major mechanism of septal destruction. NFAs downregulated both Cat S expression and activity in AMs of wild-type mice, but only inhibited its activity in AMs of PPARγ knockout mice, pointing to a PPARγ-independent mechanism of enzyme inhibition. We hypothesized that this mechanism was electrophilic S-alkylation of target Cat S cysteines, and found that NFAs bind directly to Cat S following treatment of intact AMs and, as suggested by in silico modeling and calculation of relevant parameters, elicit S-alkylation of Cys25 when incubated with purified Cat S. These results demonstrate that NFAs' electrophilic activity, in addition to their role as PPARγ agonists, underlies their protective effects in chronic obstructive pulmonary disease (COPD) and support their therapeutic potential in this disease.

  14. AMPK Activation Prevents and Reverses Drug-Induced Mitochondrial and Hepatocyte Injury by Promoting Mitochondrial Fusion and Function.

    Directory of Open Access Journals (Sweden)

    Sun Woo Sophie Kang

    Full Text Available Mitochondrial damage is the major factor underlying drug-induced liver disease but whether conditions that thwart mitochondrial injury can prevent or reverse drug-induced liver damage is unclear. A key molecule regulating mitochondria quality control is AMP activated kinase (AMPK. When activated, AMPK causes mitochondria to elongate/fuse and proliferate, with mitochondria now producing more ATP and less reactive oxygen species. Autophagy is also triggered, a process capable of removing damaged/defective mitochondria. To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac. In the absence of AMPK activation, the drugs caused hepatocytes to lose polarized morphology and have significantly decreased ATP levels and viability. At the subcellular level, mitochondria underwent fragmentation and had decreased membrane potential due to decreased expression of the mitochondrial fusion proteins Mfn1, 2 and/or Opa1. Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects. The mitochondria became highly fused and ATP production increased, and hepatocytes maintained polarized morphology. In exploring the mechanism responsible for this preventive and reversal effect, we found that AMPK activation prevented drug-mediated decreases in Mfn1, 2 and Opa1. AMPK activation also stimulated autophagy/mitophagy, most significantly in acetaminophen-treated cells. These results suggest that activation of AMPK prevents/reverses drug-induced mitochondrial and hepatocellular damage through regulation of mitochondrial fusion and autophagy, making it a potentially valuable approach for treatment of drug-induced liver injury.

  15. AMPK Activation Prevents and Reverses Drug-Induced Mitochondrial and Hepatocyte Injury by Promoting Mitochondrial Fusion and Function

    Science.gov (United States)

    Taniane, Caitlin; Farrell, Geoffrey; Arias, Irwin M.; Lippincott-Schwartz, Jennifer; Fu, Dong

    2016-01-01

    Mitochondrial damage is the major factor underlying drug-induced liver disease but whether conditions that thwart mitochondrial injury can prevent or reverse drug-induced liver damage is unclear. A key molecule regulating mitochondria quality control is AMP activated kinase (AMPK). When activated, AMPK causes mitochondria to elongate/fuse and proliferate, with mitochondria now producing more ATP and less reactive oxygen species. Autophagy is also triggered, a process capable of removing damaged/defective mitochondria. To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac. In the absence of AMPK activation, the drugs caused hepatocytes to lose polarized morphology and have significantly decreased ATP levels and viability. At the subcellular level, mitochondria underwent fragmentation and had decreased membrane potential due to decreased expression of the mitochondrial fusion proteins Mfn1, 2 and/or Opa1. Adding AICAR, a specific AMPK activator, at the time of drug exposure prevented and reversed these effects. The mitochondria became highly fused and ATP production increased, and hepatocytes maintained polarized morphology. In exploring the mechanism responsible for this preventive and reversal effect, we found that AMPK activation prevented drug-mediated decreases in Mfn1, 2 and Opa1. AMPK activation also stimulated autophagy/mitophagy, most significantly in acetaminophen-treated cells. These results suggest that activation of AMPK prevents/reverses drug-induced mitochondrial and hepatocellular damage through regulation of mitochondrial fusion and autophagy, making it a potentially valuable approach for treatment of drug-induced liver injury. PMID:27792760

  16. Reversible pH-dependent activation/inactivation of CF(1-ATPase of spinach chloroplasts

    Directory of Open Access Journals (Sweden)

    A. P. Khomochkin

    2017-08-01

    Full Text Available The aim of the work was to study the reverse pH-dependent regulation of the enzymatic activity of the catalytic part of ATP synthase (EC 3.6.3.14 of chloroplast – coupling factor CF1. It was shown that the short-term incubation of isolated CF1 in the media with pH 4.5 or 3.5 leads to inactivation of Ca2+-ATPase, which is rapidly (t1/2 ~ 1 min restored in the medium containing 0.5-10 mM bicarbonate at pH 7.8. After acid treatment, the rate of Mg2+-ATPase reaction was also stimulated in the presence of 1 mM bicarbonate (рН 7.8; 37 °С. The increase in Ca2+– and Mg2+-АТР activity of CF1 associated with the addition of NaHCO3 solution was completely eliminated after the introduction of 50 mM acetazolamide – a specific inhibitor of carbonic anhydrase. The obtained results suggest the existence of the bound bicarbonate in the CF1 structure, which apparently participates in proton transfer.

  17. A comparative study of reverse osmosis and activated charcoal, two inexpensive and very effective ways to remove waterborne radon

    International Nuclear Information System (INIS)

    Sullivan, K.T.; Mose, D.G.; Mushrush, G.W.

    1994-01-01

    A two year comparative study of waterborne radon removal reveals that reverse osmosis is consistently more effective than the use of activated charcoal. Reverse osmosis is a process by which water is forced under a pressure sufficient to overcome osmotic pressure through a semipermeable membrane, leaving behind impurities. Removal effectiveness for dissolved organic, dissolved ionic and suspended impurities are typically above 90%. Systems designed for home use to remove impurities from water dispensed at a convenient tap cost about $2000 and commonly consist of a sediment filter, a carbon prefilter, and a reverse osmosis container. A tank of activated charcoal can work equally well, and cost $500-$1000. However, the tank of charcoal becomes measurably enriched in gamma-emitters

  18. Evidence for a relief of repression mechanism for activation of the human telomerase reverse transcriptase promoter.

    Science.gov (United States)

    Wang, Shuwen; Zhu, Jiyue

    2003-05-23

    The transcriptional activation of human telomerase reverse transcriptase (hTERT) is an important step during cellular immortalization and tumorigenesis. To study how this activation occurs during immortalization, we have established a set of genetically related pre-crisis cells and their immortal progeny. As expected, hTERT mRNA was detected in our telomerase-positive immortal cells but not in pre-crisis cells or telomerase-negative immortal cells. However, transiently transfected luciferase reporters controlled by hTERT promoter sequences exhibited similar levels of luciferase activity in both telomerase-positive and -negative cells, suggesting that the endogenous chromatin context is likely required for hTERT regulation. Analysis of chromatin susceptibility to DNase I digestion consistently identified a DNase I hypersensitivity site (DHS) near the hTERT transcription initiation site in telomerase-positive cells. In addition, the histone deacetylase inhibitor trichostatin A (TSA) induced hTERT transcription and also a general increase in chromatin sensitivity to DNase treatment in telomerase-negative cells. The TSA-induced hTERT transcription in pre-crisis cells was accompanied by the formation of a DHS at the hTERT promoter. Furthermore, the TSA-induced hTERT transcription and chromatin alterations were not blocked by cycloheximide, suggesting that this induction does not require de novo protein synthesis and that TSA induces hTERT expression through the inhibition of histone deacetylation at the hTERT promoter. Taken together, our results suggest that the endogenous chromatin environment plays a critical role in the regulation of hTERT expression during cellular immortalization.

  19. Patient Activity Levels After Reverse Total Shoulder Arthroplasty: What Are Patients Doing?

    Science.gov (United States)

    Garcia, Grant H; Taylor, Samuel A; DePalma, Brian J; Mahony, Gregory T; Grawe, Brian M; Nguyen, Joseph; Dines, Joshua S; Dines, David M; Warren, Russell F; Craig, Edward V; Gulotta, Lawrence V

    2015-11-01

    The indications for reverse total shoulder arthroplasty (RTSA) continue to expand, which has resulted in younger patients who want to remain active after RTSA. Little information is available to manage expectations of both physicians and patients for return to sporting activities. To determine the rate of return to sporting activities and assess average time to return to sports after RTSA. Case series; Level of evidence, 4. This was a retrospective review of consecutive RTSA patients collected from our institution's shoulder arthroplasty registry. All patients who played sports preoperatively and had a minimum of 1-year follow-up were included. Final follow-up consisted of an additional patient-reported questionnaire with questions regarding physical fitness and sporting activities. Each patient also completed an assessment with the American Shoulder and Elbow Society (ASES) Shoulder Score and a visual analog scale (VAS) for pain. Seventy-six patients played a sport preoperatively and met inclusion and exclusion criteria. The average follow-up was 31.6 months (range, 12-65 months), and average age was 74.8 years (range, 49.9-92.6 years). Average VAS pain scores improved from 6.57 to 0.63 (P sport. Average time to return to full sports was 5.3 months. Fitness sports had the highest direct rate of return (81.5%), followed by swimming (66.7%), running (57.1%), cycling (50.0%), and golf (50%). Postoperatively, 41.1% of patients reported improved physical fitness; 88.2% felt that their sports outcome was good to excellent, and 93.4% felt that their surgical outcome was good to excellent. Patients undergoing RTSA had an 85% rate of return to 1 or more sporting activities at an average of 5.3 months after surgery. Age greater than 70 years was a significant predictor of decreased return to activities. The present study offers valuable information to help manage patient and surgeon expectations. © 2015 The Author(s).

  20. Reverse transcriptase genes are highly abundant and transcriptionally active in marine plankton assemblages

    KAUST Repository

    Lescot, Magali

    2015-11-27

    Genes encoding reverse transcriptases (RTs) are found in most eukaryotes, often as a component of retrotransposons, as well as in retroviruses and in prokaryotic retroelements. We investigated the abundance, classification and transcriptional status of RTs based on Tara Oceans marine metagenomes and metatranscriptomes encompassing a wide organism size range. Our analyses revealed that RTs predominate large-size fraction metagenomes (>5 μm), where they reached a maximum of 13.5% of the total gene abundance. Metagenomic RTs were widely distributed across the phylogeny of known RTs, but many belonged to previously uncharacterized clades. Metatranscriptomic RTs showed distinct abundance patterns across samples compared with metagenomic RTs. The relative abundances of viral and bacterial RTs among identified RT sequences were higher in metatranscriptomes than in metagenomes and these sequences were detected in all metatranscriptome size fractions. Overall, these observations suggest an active proliferation of various RT-assisted elements, which could be involved in genome evolution or adaptive processes of plankton assemblage.

  1. Active Upper-atmosphere Chemistry and Dynamics from Polar Circulation Reversal on Titan

    Science.gov (United States)

    Teanby, Nicholas A.; Irwin, Patrick Gerard Joseph; Nixon, Conor A.; DeKok, Remco; Vinatier, Sandrine; Coustenis, Athena; Sefton-Nash, Elliot; Calcutt, Simon B.; Flasar, Michael F.

    2012-01-01

    Saturn's moon Titan has a nitrogen atmosphere comparable to Earth's, with a surface pressure of 1.4 bar. Numerical models reproduce the tropospheric conditions very well but have trouble explaining the observed middle-atmosphere temperatures, composition and winds. The top of the middle-atmosphere circulation has been thought to lie at an altitude of 450 to 500 kilometres, where there is a layer of haze that appears to be separated from the main haze deck. This 'detached' haze was previously explained as being due to the colocation of peak haze production and the limit of dynamical transport by the circulation's upper branch. Herewe report a build-up of trace gases over the south pole approximately two years after observing the 2009 post-equinox circulation reversal, from which we conclude that middle-atmosphere circulation must extend to an altitude of at least 600 kilometres. The primary drivers of this circulation are summer-hemisphere heating of haze by absorption of solar radiation and winter-hemisphere cooling due to infrared emission by haze and trace gases; our results therefore imply that these effects are important well into the thermosphere (altitudes higher than 500 kilometres). This requires both active upper-atmosphere chemistry, consistent with the detection of high-complexity molecules and ions at altitudes greater than 950 kilometres, and an alternative explanation for the detached haze, such as a transition in haze particle growth from monomers to fractal structures.

  2. Reversible antispermatogenic and antisteroidogenic activities of Feronia limonia fruit pulp in adult male rats

    Science.gov (United States)

    Dhanapal, Ramaiyan; Ratna, J.Vijaya; Sarathchandran, I.; Gupta, Malaya

    2012-01-01

    Objective To explore the antispermatogenic and testicular antisteroidogenic activities of Feronia limonia fruit pulp southern India. Methods Fourty Wistar male albino rats (Rattus norvegicus) were equally divided into four groups. Experimental groups were administered with the ethanolic extract of Feronia limonia (F. limoni) fruit pulp at doses of 250 and 500 mg/kg body weight once daily for 55 days. All treated rats had corresponding recovery groups. At the end of each treatment periods, various spermatological indices, tissue biochemicals and testicular enzymes levels were analysed. Blood profiles were also estimated. Results Compared with the control, the F. limonia fruit pulp at both dose levels did not decrease body weight, which were associated with decline in epididymal sperm count, motility, viability and increased percent of abnormal sperm. Further, F. limonia fruit pulp at 500 mg/kg body weight markedly reduced the epididymal and testicular protein content by 24.58% and 29.86%, respectively, as well as the glucose-6-phosphate dehydrogenase and Δ5-3β-hydroxy steroid dehydrogenase) levels by 42.82% and 38.08%, respectively, while a significant elevation was observed in testicular cholesterol and ascorbic acid content. A gradual recovery of all parameters was observed after 55 days of treatment withdrawal. No significant alterations in haematological indices were observed. Conclusions The present findings indicate that F. limonia fruit pulp may have reversible antispermatogenic and antisteroidogenic properties, and could partially support the traditional use as male contraceptive. PMID:23569995

  3. Naltrexone Reverses Ethanol Preference and Protein Kinase C Activation in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Rajeswari Koyyada

    2018-03-01

    Full Text Available Alcohol use disorder (AUD is a major health, social and economic problem for which there are few effective treatments. The opiate antagonist naltrexone is currently prescribed clinically with mixed success. We have used naltrexone in an established behavioral assay (CAFE in Drosophila melanogaster that measures the flies' preference for ethanol-containing food. We have confirmed that Drosophila exposed to ethanol develop a preference toward this drug and we demonstrate that naltrexone, in a dose dependant manner, reverses the ethanol-induced ethanol preference. This effect is not permanent, as preference for alcohol returns after discontinuing naltrexone. Additionally, naltrexone reduced the alcohol-induced increase in protein kinase C activity. These findings are of interest because they confirm that Drosophila is a useful model for studying human responses to addictive drugs. Additionally because of the lack of a closely conserved opiate system in insects, our results could either indicate that a functionally related system does exist in insects or that in insects, and potentially also in mammals, naltrexone binds to alternative sites. Identifying such sites could lead to improved treatment strategies for AUD.

  4. Naltrexone Reverses Ethanol Preference and Protein Kinase C Activation in Drosophila melanogaster

    Science.gov (United States)

    Koyyada, Rajeswari; Latchooman, Nilesh; Jonaitis, Julius; Ayoub, Samir S.; Corcoran, Olivia; Casalotti, Stefano O.

    2018-01-01

    Alcohol use disorder (AUD) is a major health, social and economic problem for which there are few effective treatments. The opiate antagonist naltrexone is currently prescribed clinically with mixed success. We have used naltrexone in an established behavioral assay (CAFE) in Drosophila melanogaster that measures the flies' preference for ethanol-containing food. We have confirmed that Drosophila exposed to ethanol develop a preference toward this drug and we demonstrate that naltrexone, in a dose dependant manner, reverses the ethanol-induced ethanol preference. This effect is not permanent, as preference for alcohol returns after discontinuing naltrexone. Additionally, naltrexone reduced the alcohol-induced increase in protein kinase C activity. These findings are of interest because they confirm that Drosophila is a useful model for studying human responses to addictive drugs. Additionally because of the lack of a closely conserved opiate system in insects, our results could either indicate that a functionally related system does exist in insects or that in insects, and potentially also in mammals, naltrexone binds to alternative sites. Identifying such sites could lead to improved treatment strategies for AUD. PMID:29593550

  5. Reverse transcriptase genes are highly abundant and transcriptionally active in marine plankton assemblages

    KAUST Repository

    Lescot, Magali; Hingamp, Pascal; Kojima, Kenji K; Villar, Emilie; Romac, Sarah; Veluchamy, Alaguraj; Boccara, Martine; Jaillon, Olivier; Ludicone, Daniele; Bowler, Chris; Wincker, Patrick; Claverie, Jean-Michel; Ogata, Hiroyuki

    2015-01-01

    Genes encoding reverse transcriptases (RTs) are found in most eukaryotes, often as a component of retrotransposons, as well as in retroviruses and in prokaryotic retroelements. We investigated the abundance, classification and transcriptional status of RTs based on Tara Oceans marine metagenomes and metatranscriptomes encompassing a wide organism size range. Our analyses revealed that RTs predominate large-size fraction metagenomes (>5 μm), where they reached a maximum of 13.5% of the total gene abundance. Metagenomic RTs were widely distributed across the phylogeny of known RTs, but many belonged to previously uncharacterized clades. Metatranscriptomic RTs showed distinct abundance patterns across samples compared with metagenomic RTs. The relative abundances of viral and bacterial RTs among identified RT sequences were higher in metatranscriptomes than in metagenomes and these sequences were detected in all metatranscriptome size fractions. Overall, these observations suggest an active proliferation of various RT-assisted elements, which could be involved in genome evolution or adaptive processes of plankton assemblage.

  6. Exploring Collaborative Reverse Subtitling for the Enhancement of Written Production Activities in English as a Second Language

    Science.gov (United States)

    Talaván, Noa; Ibáñez, Ana; Bárcena, Elena

    2017-01-01

    This article explores the effects of collaborative reverse subtitling as an activity for the promotion of writing skills in English as a second language. An initial analysis is undertaken of the pros and cons of the role of translation in second language learning historically and the role of information and communication technology in this…

  7. DNA-directed control of enzyme-inhibitor complex formation: a modular approach to reversibly switch enzyme activity

    NARCIS (Netherlands)

    Janssen, B.M.G.; Engelen, W.; Merkx, M.

    2015-01-01

    DNA-templated reversible assembly of an enzyme–inhibitor complex is presented as a new and highly modular approach to control enzyme activity. TEM1-ß-lactamase and its inhibitor protein BLIP were conjugated to different oligonucleotides, resulting in enzyme inhibition in the presence of template

  8. Reverse electron flow-induced ROS production is attenuated by activation of mitochondrial Ca2+-sensitive K+ channels

    NARCIS (Netherlands)

    Heinen, André; Aldakkak, Mohammed; Stowe, David F.; Rhodes, Samhita S.; Riess, Matthias L.; Varadarajan, Srinivasan G.; Camara, Amadou K. S.

    2007-01-01

    Mitochondria generate reactive oxygen species (ROS) dependent on substrate conditions, O(2) concentration, redox state, and activity of the mitochondrial complexes. It is well known that the FADH(2)-linked substrate succinate induces reverse electron flow to complex I of the electron transport chain

  9. The management challenge for household waste in emerging economies like Brazil: realistic source separation and activation of reverse logistics.

    Science.gov (United States)

    Fehr, M

    2014-09-01

    Business opportunities in the household waste sector in emerging economies still evolve around the activities of bulk collection and tipping with an open material balance. This research, conducted in Brazil, pursued the objective of shifting opportunities from tipping to reverse logistics in order to close the balance. To do this, it illustrated how specific knowledge of sorted waste composition and reverse logistics operations can be used to determine realistic temporal and quantitative landfill diversion targets in an emerging economy context. Experimentation constructed and confirmed the recycling trilogy that consists of source separation, collection infrastructure and reverse logistics. The study on source separation demonstrated the vital difference between raw and sorted waste compositions. Raw waste contained 70% biodegradable and 30% inert matter. Source separation produced 47% biodegradable, 20% inert and 33% mixed material. The study on collection infrastructure developed the necessary receiving facilities. The study on reverse logistics identified private operators capable of collecting and processing all separated inert items. Recycling activities for biodegradable material were scarce and erratic. Only farmers would take the material as animal feed. No composting initiatives existed. The management challenge was identified as stimulating these activities in order to complete the trilogy and divert the 47% source-separated biodegradable discards from the landfills. © The Author(s) 2014.

  10. Neural network classifications and correlation analysis of EEG and MEG activity accompanying spontaneous reversals of the Necker cube.

    Science.gov (United States)

    Gaetz, M; Weinberg, H; Rzempoluck, E; Jantzen, K J

    1998-04-01

    It has recently been suggested that reentrant connections are essential in systems that process complex information [A. Damasio, H. Damasio, Cortical systems for the retrieval of concrete knowledge: the convergence zone framework, in: C. Koch, J.L. Davis (Eds.), Large Scale Neuronal Theories of the Brain, The MIT Press, Cambridge, 1995, pp. 61-74; G. Edelman, The Remembered Present, Basic Books, New York, 1989; M.I. Posner, M. Rothbart, Constructing neuronal theories of mind, in: C. Koch, J.L. Davis (Eds.), Large Scale Neuronal Theories of the Brain, The MIT Press, Cambridge, 1995, pp. 183-199; C. von der Malsburg, W. Schneider, A neuronal cocktail party processor, Biol. Cybem., 54 (1986) 29-40]. Reentry is not feedback, but parallel signalling in the time domain between spatially distributed maps, similar to a process of correlation between distributed systems. Accordingly, it was expected that during spontaneous reversals of the Necker cube, complex patterns of correlations between distributed systems would be present in the cortex. The present study included EEG (n=4) and MEG recordings (n=5). Two experimental questions were posed: (1) Can distributed cortical patterns present during perceptual reversals be classified differently using a generalised regression neural network (GRNN) compared to processing of a two-dimensional figure? (2) Does correlated cortical activity increase significantly during perception of a Necker cube reversal? One-second duration single trials of EEG and MEG data were analysed using the GRNN. Electrode/sensor pairings based on cortico-cortical connections were selected to assess correlated activity in each condition. The GRNN significantly classified single trials recorded during Necker cube reversals as different from single trials recorded during perception of a two-dimensional figure for both EEG and MEG. In addition, correlated cortical activity increased significantly in the Necker cube reversal condition for EEG and MEG compared

  11. Thermally activated magnetization reversal in monatomic magnetic chains on surfaces studied by classical atomistic spin-dynamics simulations

    International Nuclear Information System (INIS)

    Bauer, David S G; Mavropoulos, Phivos; Bluegel, Stefan; Lounis, Samir

    2011-01-01

    We analyse the spontaneous magnetization reversal of supported monatomic chains of finite length due to thermal fluctuations via atomistic spin-dynamics simulations. Our approach is based on the integration of the Landau-Lifshitz equation of motion of a classical spin Hamiltonian in the presence of stochastic forces. The associated magnetization lifetime is found to obey an Arrhenius law with an activation barrier equal to the domain wall energy in the chain. For chains longer than one domain wall width, the reversal is initiated by nucleation of a reversed magnetization domain primarily at the chain edge followed by a subsequent propagation of the domain wall to the other edge in a random-walk fashion. This results in a linear dependence of the lifetime on the chain length, if the magnetization correlation length is not exceeded. We studied chains of uniaxial and triaxial anisotropy and found that a triaxial anisotropy leads to a reduction of the magnetization lifetime due to a higher reversal attempt rate, even though the activation barrier is not changed.

  12. Damping Dependence of Reversal Magnetic Field on Co-based Nano-Ferromagnetic with Thermal Activation

    Directory of Open Access Journals (Sweden)

    Nadia Ananda Herianto

    2015-02-01

    Full Text Available Currently, hard disk development has used HAMR technology that applies heat to perpendicular media until near Curie temperature, then cools it down to room temperature. The use of HAMR technology is significantly influence by Gilbert damping constants. Damping affects the magnetization reversal and coercivity field. Simulation is used to evaluate magnetization reversal by completing Landau-Lifshitz-Gilbert explicit equation. A strong ferromagnetic cobalt based material with size 50×50×20 nm3 is used which parameters are anisotropy materials 3.51×106 erg/cm3, magnetic saturation 5697.5 G, exchange constant 1×10-7 erg/cm, and various Gilbert damping from 0.09 to 0.5. To observe the thermal effect, two schemes are used which are Reduced Barrier Writing and Curie Point Writing. As a result, materials with high damping is able to reverse the magnetizations faster and reduce the energy barrier. Moreover, it can lower the minimum field to start the magnetizations reversal, threshold field, and probability rate. The heating near Curie temperature has succeeded in reducing the reversal field to 1/10 compared to writing process in absence of thermal field.

  13. A 3D QSAR pharmacophore model and quantum chemical structure--activity analysis of chloroquine(CQ)-resistance reversal.

    Science.gov (United States)

    Bhattacharjee, Apurba K; Kyle, Dennis E; Vennerstrom, Jonathan L; Milhous, Wilbur K

    2002-01-01

    Using CATALYST, a three-dimensional QSAR pharmacophore model for chloroquine(CQ)-resistance reversal was developed from a training set of 17 compounds. These included imipramine (1), desipramine (2), and 15 of their analogues (3-17), some of which fully reversed CQ-resistance, while others were without effect. The generated pharmacophore model indicates that two aromatic hydrophobic interaction sites on the tricyclic ring and a hydrogen bond acceptor (lipid) site at the side chain, preferably on a nitrogen atom, are necessary for potent activity. Stereoelectronic properties calculated by using AM1 semiempirical calculations were consistent with the model, particularly the electrostatic potential profiles characterized by a localized negative potential region by the side chain nitrogen atom and a large region covering the aromatic ring. The calculated data further revealed that aminoalkyl substitution at the N5-position of the heterocycle and a secondary or tertiary aliphatic aminoalkyl nitrogen atom with a two or three carbon bridge to the heteroaromatic nitrogen (N5) are required for potent "resistance reversal activity". Lowest energy conformers for 1-17 were determined and optimized to afford stereoelectronic properties such as molecular orbital energies, electrostatic potentials, atomic charges, proton affinities, octanol-water partition coefficients (log P), and structural parameters. For 1-17, fairly good correlation exists between resistance reversal activity and intrinsic basicity of the nitrogen atom at the tricyclic ring system, frontier orbital energies, and lipophilicity. Significantly, nine out of 11 of a group of structurally diverse CQ-resistance reversal agents mapped very well on the 3D QSAR pharmacophore model.

  14. Activation and waste disposal of the TITAN RFP [reversed-field-pinch] reactors

    International Nuclear Information System (INIS)

    Cheng, E.T.; Conn, R.W.

    1988-01-01

    The TITAN-I lithium self-cooled and TITAN-II aqueous lithium nitrate solution-cooled fusion reactors are based on the reversed-field-pinch (RFP) toroidal confinement concept and operate at high power density with an 18.1 MW/m 2 neutron wall loading. These designs were analyzed to study the activation and waste disposal aspects of such high-power density reactors. It was found that because of the use of V-3Ti-1Si (TITAN-I) and reduced activation ferritic steel (TITAN-II) as structural alloys for the first wall, blanket, reflector, and shield components, all the TITAN components except the divertor collector plates can be classified as shallow-land burial (10CFR61 Class C or better) nuclear waste for disposal, provided that the impurity elements, niobium and molybdenum, can be controlled below about 1 and 0.3 appm levels, respectively. The average annual disposal masses were estimated to be 150 and 96 tonnes, respectively, for the 1,000 MW TITAN-I and TITAN-II reactors. This corresponds to about 11% of the total mass in the fusion power core of both reactors. The divertor collector plates are fabricated with tungsten because of its low particle sputtering properties. These divertor collector plates in the TITAN-I reactor will be qualified as Class C waste after 18.1 MW-y/m 2 operation. The waste disposal rating of the divertor collector plates in the TITAN-II reactor, however, is estimated to be a factor of 4 higher than allowed for Class C disposal, because of the soft neutron spectrum in the beryllium environment. The annual disposal mass of this non-Class C waste is 0.35 tons, about 0.04% of the average annual discharge mass for the TITAN-II reactor. An additional 74 m 3 annual discharge of Class C waste containing 14 C may be needed for the TITAN-II reactor because of the use of nitrate salt in the aqueous coolant as the tritium breeder. 13 refs., 6 tabs

  15. Chemogenetic locus coeruleus activation restores reversal learning in a rat model of Alzheimer's disease.

    Science.gov (United States)

    Rorabaugh, Jacki M; Chalermpalanupap, Termpanit; Botz-Zapp, Christian A; Fu, Vanessa M; Lembeck, Natalie A; Cohen, Robert M; Weinshenker, David

    2017-11-01

    See Grinberg and Heinsen (doi:10.1093/brain/awx261) for a scientific commentary on this article. Clinical evidence suggests that aberrant tau accumulation in the locus coeruleus and noradrenergic dysfunction may be a critical early step in Alzheimer’s disease progression. Yet, an accurate preclinical model of these phenotypes that includes early pretangle tau accrual in the locus coeruleus, loss of locus coeruleus innervation and deficits locus coeruleus/norepinephrine modulated behaviours, does not exist, hampering the identification of underlying mechanisms and the development of locus coeruleus-based therapies. Here, a transgenic rat (TgF344-AD) expressing disease-causing mutant amyloid precursor protein (APPsw) and presenilin-1 (PS1ΔE9) was characterized for histological and behavioural signs of locus coeruleus dysfunction reminiscent of mild cognitive impairment/early Alzheimer’s disease. In TgF344-AD rats, hyperphosphorylated tau was detected in the locus coeruleus prior to accrual in the medial entorhinal cortex or hippocampus, and tau pathology in the locus coeruleus was negatively correlated with noradrenergic innervation in the medial entorhinal cortex. Likewise, TgF344-AD rats displayed progressive loss of hippocampal norepinephrine levels and locus coeruleus fibres in the medial entorhinal cortex and dentate gyrus, with no frank noradrenergic cell body loss. Cultured mouse locus coeruleus neurons expressing hyperphosphorylation-prone mutant human tau had shorter neurites than control neurons, but similar cell viability, suggesting a causal link between pretangle tau accrual and altered locus coeruleus fibre morphology. TgF344-AD rats had impaired reversal learning in the Morris water maze compared to their wild-type littermates, which was rescued by chemogenetic locus coeruleus activation via designer receptors exclusively activated by designer drugs (DREADDs). Our results indicate that TgF344-AD rats uniquely meet several key criteria for a

  16. Intestinal myoelectric activity and contractile motility in dogs with a reversed jejunal segment after extensive small bowel resection.

    Science.gov (United States)

    Uchiyama, M; Iwafuchi, M; Ohsawa, Y; Yagi, M; Iinuma, Y; Ohtani, S

    1992-06-01

    To evaluate the functioning and effectiveness of a reversed jejunal segment after extensive small bowel resection, we continuously measured the postoperative bowel motility (using bipolar electrodes and/or contractile strain gage force transducers) in interdigestive and postprandial conscious dogs at 2 to 5 weeks after surgery. The fasting duodenal migrating myoelectric (or motor) complex (MMC) occurred at markedly longer intervals in dogs with a 20-cm reversed jejunal segment created after 75% to 80% extensive small bowel resection (group 3) than in dogs that received extensive resection alone (group 2) or dogs that underwent construction of a reversed jejunal segment without bowel resection (group 1). The MMC arising from the duodenum was often interrupted at the jejunum above the proximal anastomosis and did not migrate smoothly to the reversed segment or terminal ileum in group 3. In addition, brief small discordant contractions were frequent in the reversed segment and the jejunum above the proximal anastomosis in group 3. The duration of the postprandial period without duodenal MMC activity was significantly prolonged in groups 2 and 3. These results suggest that the transit time and passage of intestinal contents were delayed and that the periodical MMC was disturbed in group 3. The delay of transit time was due to prolongation of the interval between duodenal MMCs, the interruption of MMC propagation at the jejunum above the proximal anastomosis, the dominance of MMCs that followed the inherent anatomical continuity of the bowel, and discordant movements across the proximal anastomosis. Functional obstruction could be a potential problem in a 20-cm reversed jejunal segment inserted after extensive small bowel resection.

  17. Activated Charge-Reversal Polymeric Nano-System: The Promising Strategy in Drug Delivery for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Yichen Hu

    2016-04-01

    Full Text Available Various polymeric nanoparticles (NPs with optimal size, tumor-targeting functionalization, or microenvironment sensitive characteristics have been designed to solve several limitations of conventional chemotherapy. Nano-sized polymeric drug carrier systems have remarkably great advantages in drug delivery and cancer therapy, which are still plagued with severe deficiencies, especially insufficient cellular uptake. Recently, surface charge of medical NPs has been demonstrated to play an important role in cellular uptake. NPs with positive charge show higher affinity to anionic cell membranes such that with more efficient cellular internalization, but otherwise cause severe aggregation and fast clearance in circulation. Thus, surface charge-reversal NPs, specifically activated at the tumor site, have shown to elegantly resolve the enhanced cellular uptake in cancer cells vs. non-specific protein adsorption dilemma. Herein, this review mainly focuses on the effect of tumor-site activated surface charge reversal NPs on tumor treatment, including the activated mechanisms and various applications in suppressing cancer cells, killing cancer stem cell and overcoming multidrug resistance, with the emphasis on recent research in these fields. With the comprehensive and in-depth understanding of the activated surface charge reversal NPs, this approach might arouse great interest of scientific research on enhanced efficient polymeric nano-carriers in cancer therapy.

  18. Soft shell clams Mya arenaria with disseminated neoplasia demonstrate reverse transcriptase activity

    Science.gov (United States)

    House, M.L.; Kim, C.H.; Reno, P.W.

    1998-01-01

    Disseminated neoplasia (DN), a proliferative cell disorder of the circulatory system of bivalves, was first reported in oysters in 1969. Since that time, the disease has been determined to be transmissible through water-borne exposure, but the etiological agent has not been unequivocally identified. In order to determine if a viral agent, possibly a retrovirus, could be the causative agent of DN, transmission experiments were performed, using both a cell-free filtrate and a sucrose gradient-purified preparation of a cell-free filtrate of DN positive materials. Additionally, a PCR-enhanced reverse transcriptase assay was used to determine if reverse transcriptase was present in tissues or hemolymph from DN positive soft shell clams Mya arenaria. DN was transmitted to healthy clams by injection with whole DN cells, but not with cell-free flitrates prepared from either tissues from DN positive clams, or DN cells. The cell-free preparations from DN-positive tissues and hemolymph having high levels of DN cells in circulation exhibited positive reactions in the PCR-enhanced reverse transcriptase assay. Cell-free preparations of hemolymph from clams having low levels of DN (<0.1% of cells abnormal), hemocytes from normal soft shell clams, and normal soft shell clam tissues did not produce a positive reaction in the PCR enhanced reverse transcriptase assay.

  19. Characterization of active reverse transcriptase and nucleoprotein complexes of the yeast retrotransposon Ty3 in vitro.

    Science.gov (United States)

    Cristofari, G; Gabus, C; Ficheux, D; Bona, M; Le Grice, S F; Darlix, J L

    1999-12-17

    Human immunodeficiency virus (HIV) and the distantly related yeast Ty3 retrotransposon encode reverse transcriptase (RT) and a nucleic acid-binding protein designated nucleocapsid protein (NCp) with either one or two zinc fingers, required for HIV-1 replication and Ty3 transposition, respectively. In vitro binding of HIV-1 NCp7 to viral 5' RNA and primer tRNA(3)(Lys) catalyzes formation of nucleoprotein complexes resembling the virion nucleocapsid. Nucleocapsid complex formation functions in viral RNA dimerization and tRNA annealing to the primer binding site (PBS). RT is recruited in these nucleoprotein complexes and synthesizes minus-strand cDNA initiated at the PBS. Recent results on yeast Ty3 have shown that the homologous NCp9 promotes annealing of primer tRNA(i)(Met) to a 5'-3' bipartite PBS, allowing RNA:tRNA dimer formation and initiation of cDNA synthesis at the 5' PBS (). To compare specific cDNA synthesis in a retrotransposon and HIV-1, we have established a Ty3 model system comprising Ty3 RNA with the 5'-3' PBS, primer tRNA(i)(Met), NCp9, and for the first time, highly purified Ty3 RT. Here we report that Ty3 RT is as active as retroviral HIV-1 or murine leukemia virus RT using a synthetic template-primer system. Moreover, and in contrast to what was found with retroviral RTs, retrotransposon Ty3 RT was unable to direct cDNA synthesis by self-priming. We also show that Ty3 nucleoprotein complexes were formed in vitro and that the N terminus of NCp9, but not the zinc finger, is required for complex formation, tRNA annealing to the PBS, RNA dimerization, and primer tRNA-directed cDNA synthesis by Ty3 RT. These results indicate that NCp9 chaperones bona fide cDNA synthesis by RT in the yeast Ty3 retrotransposon, as illustrated for NCp7 in HIV-1, reinforcing the notion that Ty3 NCp9 is an ancestor of HIV-1 NCp7.

  20. Silent information regulator 1 (SIRT1) ameliorates liver fibrosis via promoting activated stellate cell apoptosis and reversion

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Yuting, E-mail: wuyuting1302@sina.com; Liu, Xuejiao; Zhou, Qun; Huang, Cheng; Meng, Xiaoming; Xu, Fengyun; Li, Jun, E-mail: lj@ahmu.edu.cn

    2015-12-01

    SIRT1 (silent information regulator 1), a conserved NAD +-dependent histone deacetylase, is closely related with various biological processes. Moreover, the important role of SIRT1 in alcoholic liver disease, nonalcoholic fatty liver and HCC had been widely reported. Recently, a novel role of SIRT1 was uncovered in organ fibrosis diseases. Here, we investigated the inhibitory effect of SIRT1 in liver fibrogenesis. SIRT1 protein was dramatically decreased in CCl4-treated mice livers. Stimulation of LX-2 cells with TGF-β1 also resulted in a significant suppression of SIRT1 protein. Nevertheless, TGF-β1-induced LX-2 cell activation was inhibited by SIRT1 plasmid, and this was accompanied by up-regulation of cell apoptosis-related proteins. Overexpression of SIRT1 also attenuated TGF-β1-induced expression of myofibroblast markers α-SMA and COL1a. However, the important characteristic of the recovery of liver fibrosis is not only the apoptosis of activated stellate cells but also the reversal of the myofibroblast-like phenotype to a quiescent-like phenotype. Restoration of SIRT1 protein was observed in the in vivo spontaneously liver fibrosis reversion model and in vitro MDI (isobutylmethylxanthine, dexamethasone, and insulin)-induced reversed stellate cells, and forced expression of SIRT1 also promoted the reversal of activated stellate cells. Furthermore, lncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) was increased in liver fibrosis. RNAi-mediated suppression of MALAT1 resulted in a decrease of myofibroblast markers and restoration of SIRT1 protein. These observations suggested that SIRT1 contributed to apoptosis and reversion of activated LX-2 cells and SIRT1 might be regulated by MALAT1 in liver fibrosis. Therefore, SIRT1 could be considered as a valuable therapeutic target for translational studies of liver fibrosis. - Highlights: • This is the first report of SIRT1 expression and function in liver fibrogenesis and reversion.

  1. Quasi-periodic fractal patterns in geomagnetic reversals, geological activity, and astronomical events

    International Nuclear Information System (INIS)

    Puetz, Stephen J.; Borchardt, Glenn

    2015-01-01

    Highlights: • Spectral analysis indicates similar harmonics in astronomical and geological events. • Quasi-periodic cycles occur in tripling patterns of 30.44, 91.33, 274, 822, and 2466 myr. • Similar astro- and geo-phases suggest that the cycles develop from a common source. - Abstract: The cause of geomagnetic reversals remains a geological mystery. With the availability of improved paleomagnetic databases in the past three years, a reexamination of possible periodicity in the geomagnetic reversal rate seems warranted. Previous reports of cyclicity in the reversal rate, along with the recent discovery of harmonic cycles in a variety of natural events, sparked our interest in reevaluating possible patterns in the reversal rate. Here, we focus on geomagnetic periodicity, but also analyze paleointensity, zircon formation, star formation, quasar formation, supernova, and gamma ray burst records to determine if patterns that occur in other types of data have similar periodicity. If so, then the degree of synchronization will indicate likely causal relationships with geomagnetic reversals. To achieve that goal, newly available time-series records from these disciplines were tested for cyclicity by using spectral analysis and time-lagged cross-correlation techniques. The results showed evidence of period-tripled cycles of 30.44, 91.33, 274, 822, and 2466 million years, corresponding to the periodicity from a new Universal Cycle model. Based on the results, a fractal model of the universe is hypothesized in which sub-electron fractal matter acts as a dynamic medium for large-scale waves that cause the cycles in astronomical and geological processes. According to this hypothesis, the medium of sub-electron fractal matter periodically compresses and decompresses according to the standard laws for mechanical waves. Consequently, the compressions contribute to high-pressure environments and vice versa for the decompressions, which are hypothesized to cause the

  2. [Effects of reversing the feeding cycle and the light period on the spontaneous activity of the rat (author's transl)].

    Science.gov (United States)

    Ticca, M

    1976-01-01

    The amount and the circadian distribution of spontaneous activity in the rat are influenced by a number of factors, whose importance and interrelationships are still deeply discussed. In order to check the reliability of previous studies about the effects of meal-eating on the spontaneous activity (wheel running) of rats of our Sprague-Dawley strain, the adjustment to the modifications of the normal day-night cycle and of the normal nocturnal feeding rhythm have been controlled. Reversing the normal light and dark periods caused the rats, after a 24 hours period, to lower and to irregularly distribute their spontaneous activity. Rats shifted their pattern of maximal activity by 12 hours in the new period of darkness in about five days, and showed to have completely fixed the new reversed running habit. Also feeding habits changed in a similar way, but more slowly. The levels of mean daily activity did not change. In a second experiment, rats, received food during light hours, and were deprived during dark hours. Their activity increased considerably and irregularly during dark hours, while a very slight rise of wheel running was shown during light hours. Body weight gain and food consumption were similar to those of the control group. These results slightly differ from those obtained using other rat strains, and are an interesting example of reinforcement of a spontaneous behavior resulting more from the light-dark cycle than from cues provided by food deprivation.

  3. Binding of Dumbbell Oligonucleotides to MoMuLV Reverse Transcriptase: Inhibitory Properties of RNase H Activity

    Directory of Open Access Journals (Sweden)

    Ajay Kumar

    2010-01-01

    Full Text Available Dumbbell oligonucleotides with loops of various chemistry were synthesized. Incubation of dumbbell oligonucleotides containing phosphorothioate bonds or trimethylene phosphate linkages in loops with S1 nuclease did not result in significant cleavage under conditions which led to the degradation of dumbbell oligonucleotide containing phophodiester bonds in the loops. The binding of reverse transcriptase of Moloney Murine Leukemia Virus (MoMuLV was evaluated with all the five oligonucleotides. The protein binds to all the dumbbell oligonucleotides with similar affinity. The dissociation constants evaluated using PAGE band mobility shift assays were of the order of 10-7. The inhibitory properties of the retroviral RNase H activity was evaluated using 3H –UTP-labeled RNA:RNA-DNA hybrid. It was found that the best dumbbell oligonucleotide, inhibitor contained phosphorothioate residues in both the loops. Our value studies demonstrated that this particularly designed oligonucleotide displays an IC50 of 18 nM in its inhibition on the reverse transcriptase RNase H activity, a magnitude lower than that of first nucleotide reverse transcriptase of HIV-1, tenofovir, introduced by Gilead Science in the market.

  4. On Variable Reverse Power Flow-Part I: Active-Reactive Optimal Power Flow with Reactive Power of Wind Stations

    Directory of Open Access Journals (Sweden)

    Aouss Gabash

    2016-02-01

    Full Text Available It has recently been shown that using battery storage systems (BSSs to provide reactive power provision in a medium-voltage (MV active distribution network (ADN with embedded wind stations (WSs can lead to a huge amount of reverse power to an upstream transmission network (TN. However, unity power factors (PFs of WSs were assumed in those studies to analyze the potential of BSSs. Therefore, in this paper (Part-I, we aim to further explore the pure reactive power potential of WSs (i.e., without BSSs by investigating the issue of variable reverse power flow under different limits on PFs in an electricity market model. The main contributions of this work are summarized as follows: (1 Introducing the reactive power capability of WSs in the optimization model of the active-reactive optimal power flow (A-R-OPF and highlighting the benefits/impacts under different limits on PFs. (2 Investigating the impacts of different agreements for variable reverse power flow on the operation of an ADN under different demand scenarios. (3 Derivation of the function of reactive energy losses in the grid with an equivalent-π circuit and comparing its value with active energy losses. (4 Balancing the energy curtailment of wind generation, active-reactive energy losses in the grid and active-reactive energy import-export by a meter-based method. In Part-II, the potential of the developed model is studied through analyzing an electricity market model and a 41-bus network with different locations of WSs.

  5. Endogenous reverse transcriptase (RT) activity and Chromatin remodeling in normal and transformed cells and early embryos

    International Nuclear Information System (INIS)

    Spadafora, C.; Sciamanna, I.; Misteli, T.

    2009-01-01

    Endogenous Reverse Transcriptase (RT) is an enzyme encoded by two classes of genomic retro-elements: retro-transposons and endogenous retroviruses. Basal levels of RT are expressed in all non pathological, differentiated tissues while high RT expression levels characterize tumorigenic cells, germ cells and embryonic tissues. Preliminary studies carried out in our laboratory have shown that RT inhibition using pharmacological inhibitors (nevirapine and efavirenz, two drugs currently used in AIDS therapy) drastically reduces cell proliferation, promotes differentiation of tumorigenic cells in vitro, induces a reprogrammed gene expression and antagonizes tumor progression in nude mice inoculated with tumorigenic human cell lines, including melanoma, prostate and colon carcinoma and microcitoma

  6. Evaluation of the treatment of reverse osmosis concentrates from municipal wastewater reclamation by coagulation and granular activated carbon adsorption.

    Science.gov (United States)

    Sun, Ying-Xue; Yang, Zhe; Ye, Tao; Shi, Na; Tian, Yuan

    2016-07-01

    Reverse osmosis concentrate (ROC) from municipal wastewater reclamation reverse osmosis (mWRRO) contains elevated concentrations of contaminants which pose potential risks to aquatic environment. The treatment of ROC from an mWRRO using granular activated carbon (GAC) combined pretreatment of coagulation was optimized and evaluated. Among the three coagulants tested, ferric chloride (FeCl3) presented relatively higher DOC removal efficiency than polyaluminium chloride and lime at the same dosage and coagulation conditions. The removal efficiency of DOC, genotoxicity, and antiestrogenic activity concentration of the ROC could achieve 16.9, 18.9, and 39.7 %, respectively, by FeCl3 coagulation (with FeCl3 dosage of 180.22 mg/L), which can hardly reduce UV254 and genotoxicity normalized by DOC of the DOM with MW activity were completely eliminated by the GAC adsorption. The results suggest that GAC adsorption combined pretreatment of FeCl3 coagulation as an efficient method to control organics, genotoxicity, and antiestrogenic activity in the ROC from mWRRO system.

  7. APOBEC3DE Inhibits LINE-1 Retrotransposition by Interacting with ORF1p and Influencing LINE Reverse Transcriptase Activity.

    Directory of Open Access Journals (Sweden)

    Weizi Liang

    Full Text Available Human long interspersed elements 1 (LINE-1 or L1 is the only autonomous non-LTR retroelement in humans and has been associated with genome instability, inherited genetic diseases, and the development of cancer. Certain human APOBEC3 family proteins are known to have LINE-1 restriction activity. The mechanisms by which APOBEC3 affects LINE-1 retrotransposition are not all well characterized; here, we confirm that both A3B and A3DE have a strong ability to inhibit LINE-1 retrotransposition. A3DE interacts with LINE-1 ORF1p to target LINE-1 ribonucleoprotein particles in an RNA-dependent manner. Moreover, A3DE binds to LINE-1 RNA and ORF1 protein in cell culture system. Fluorescence microscopy demonstrated that A3DE co-localizes with ORF1p in cytoplasm. Furthermore, A3DE inhibits LINE-1 reverse transcriptase activity in LINE-1 ribonucleoprotein particles in a cytidine deaminase-independent manner. In contrast, A3B has less inhibitory effects on LINE-1 reverse transcriptase activity despite its strong inhibition of LINE-1 retrotransposition. This study demonstrates that different A3 proteins have been evolved to inhibit LINE-1 activity through distinct mechanisms.

  8. Reverse Algols

    Science.gov (United States)

    Leung, K. C.

    1989-01-01

    Reverse Algols, binary systems with a semidetached configuration in which the more massive component is in contact with the critical equipotential surface, are examined. Observational evidence for reverse Algols is presented and the parameters of seven reverse Algols are listed. The evolution of Algols and reverse Algols is discussed. It is suggested that, because reverse Algols represent the premass-reversal semidetached phase of close binary evolution, the evolutionary time scale between regular and reverse Algols is the ratio of the number of confirmed systems of these two Algol types.

  9. Regulating the Access to Awareness: Brain Activity Related to Probe-related and Spontaneous Reversals in Binocular Rivalry.

    Science.gov (United States)

    Metzger, Brian A; Mathewson, Kyle E; Tapia, Evelina; Fabiani, Monica; Gratton, Gabriele; Beck, Diane M

    2017-06-01

    Research on the neural correlates of consciousness (NCC) has implicated an assortment of brain regions, ERP components, and network properties associated with visual awareness. Recently, the P3b ERP component has emerged as a leading NCC candidate. However, typical P3b paradigms depend on the detection of some stimulus change, making it difficult to separate brain processes elicited by the stimulus itself from those associated with updates or changes in visual awareness. Here we used binocular rivalry to ask whether the P3b is associated with changes in awareness even in the absence of changes in the object of awareness. We recorded ERPs during a probe-mediated binocular rivalry paradigm in which brief probes were presented over the image in either the suppressed or dominant eye to determine whether the elicited P3b activity is probe or reversal related. We found that the timing of P3b (but not its amplitude) was closely related to the timing of the report of a perceptual change rather than to the onset of the probe. This is consistent with the proposal that P3b indexes updates in conscious awareness, rather than being related to stimulus processing per se. Conversely, the probe-related P1 amplitude (but not its latency) was associated with reversal latency, suggesting that the degree to which the probe is processed increases the likelihood of a fast perceptual reversal. Finally, the response-locked P3b amplitude (but not its latency) was associated with the duration of an intermediate stage between reversals in which parts of both percepts coexist (piecemeal period). Together, the data suggest that the P3b reflects an update in consciousness and that the intensity of that process (as indexed by P3b amplitude) predicts how immediate that update is.

  10. Reverse Logistics

    OpenAIRE

    Kulikova, Olga

    2016-01-01

    This thesis was focused on the analysis of the concept of reverse logistics and actual reverse processes which are implemented in mining industry and finding solutions for the optimization of reverse logistics in this sphere. The objective of this paper was the assessment of the development of reverse logistics in mining industry on the example of potash production. The theoretical part was based on reverse logistics and mining waste related literature and provided foundations for further...

  11. Reversible anti-settlement activity against Amphibalanus (= Balanus ) amphitrite, Bugula neritina , and Hydroides elegans by a nontoxic pharmaceutical compound, mizolastine

    KAUST Repository

    Zhou, Xiaojian

    2009-11-01

    Mizolastine, an antihistamine pharmaceutical, was found to significantly inhibit larval settlement of the barnacle Amphibalanus (=Balanus) amphitrite, the bryozoan Bugula neritina, and the polychaete Hydroides elegans with EC50 values of 4.2, 11.2, and 4.1 mg ml-1, respectively. No toxicity against the larvae of these three species was observed at the concentration range tested during incubations with mizolastine. To determine whether the anti-settlement activity of mizolastine is reversible, recovery bioassays using these three species were conducted. More than 70% of the larvae that had been exposed for 4 h to mizolastine at concentrations four-fold greater than their respective EC50 values completed normal metamorphosis. The results of the recovery bioassay provide evidence that the antisettlement effect of mizolastine is reversible in addition to being nontoxic. The anti-settlement activities of several intermediates of the synthesis process of mizolastine were also examined. One of the intermediates, 2-chloro-1-(4- fluorobenzyl)-1H-benzo[d]imidazole, inhibited larval settlement and metamorphosis with low toxicity. These results may improve the understanding of the key functional group responsible for the anti-settlement activity of mizolastine. © 2009 Taylor & Francis.

  12. Leptin upregulates telomerase activity and transcription of human telomerase reverse transcriptase in MCF-7 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Ren, He, E-mail: herenrh@yahoo.com.cn [Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin Medical University Cancer Hospital, Tianjin (China); Zhao, Tiansuo; Wang, Xiuchao; Gao, Chuntao; Wang, Jian; Yu, Ming [Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin Medical University Cancer Hospital, Tianjin (China); Hao, Jihui, E-mail: jihuihao@yahoo.com [Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin Medical University Cancer Hospital, Tianjin (China)

    2010-03-26

    The aim was to analyze the mechanism of leptin-induced activity of telomerase in MCF-7 breast cancer cells. We found that leptin activated telomerase in a dose-dependent manner; leptin upregulated the expression of Human Telomerase Reverse Transcriptase (hTERT) at mRNA and protein levels; blockade of signal transducer and activator of transcription 3 (STAT3) phosphorylation significantly counteracted leptin-induced hTERT transcription and protein expression; chromatin immunoprecipitation analysis showed that leptin enhanced the binding of STAT3 to the hTERT promoter. This study uncovers a new mechanism of the proliferative effect of leptin on breast cancer cells and provides a new explanation of obesity-related breast cancer.

  13. The role of PTEN in regulation of hepatic macrophages activation and function in progression and reversal of liver fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Yahui; Tian, Yuanyao; Xia, Jialu; Wu, Xiaoqin; Yang, Yang; Li, Xiaofeng; Huang, Cheng; Meng, Xiaoming; Ma, Taotao; Li, Jun, E-mail: lj@ahmu.edu.cn

    2017-02-15

    Activation of Kupffer cells (KCs) plays a pivotal role in the pathogenesis of liver fibrosis. The progression and reversal of CCl{sub 4}-induced mouse liver fibrosis showed a mixed induction of hepatic classical (M1) and alternative (M2) macrophage markers. Although the role of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in modulating myeloid cell activation has recently been identified, its function in macrophage activation during hepatic fibrosis remains to be fully appreciated. In our study, PTEN expression of KCs was remarkably decreased in CCl{sub 4}-induced mice but increased to a near-normal level in reversed mice. Moreover, PTEN was significantly decreased in IL4-induced RAW 264.7 cells in vitro and lower expression of PTEN was observed in M2 macrophages in vivo. In addition, loss- and gain-of-function studies suggested that PTEN regulates M2 macrophages polarization via activation of PI3K/Akt/STAT6 signaling, but had a limited effect on M1 macrophages polarization in vitro. Additionally, Ly294002, a chemical inhibitor of PI3K/Akt, could dramatically down-regulate the hallmarks of M2 macrophages. In conclusion, PTEN mediates macrophages activation by PI3K/Akt/STAT6 signaling pathway, which provides novel compelling evidences on the potential of PTEN in liver injury and opens new cellular target for the pharmacological therapy of liver fibrosis. - Highlights: • CCl{sub 4} treatment triggered a mixed M1/M2 macrophage phenotype in fibrosis. • Lower expression of PTEN in murine M2 macrophages in vivo and vitro. • PTEN modulates M2 macrophages activation via PI3K/Akt/STAT6 signaling. • Provide a new cellular target modulate macrophage mediated hepatic fibrosis.

  14. Ultrasonic Stimulation of Mouse Skin Reverses the Healing Delays in Diabetes and Aging by Activation of Rac1.

    Science.gov (United States)

    Roper, James A; Williamson, Rosalind C; Bally, Blandine; Cowell, Christopher A M; Brooks, Rebecca; Stephens, Phil; Harrison, Andrew J; Bass, Mark D

    2015-11-01

    Chronic skin-healing defects are one of the leading challenges to lifelong well-being, affecting 2-5% of populations. Chronic wound formation is linked to age and diabetes and frequently leads to major limb amputation. Here we identify a strategy to reverse fibroblast senescence and improve healing rates. In healthy skin, fibronectin activates Rac1 in fibroblasts, causing migration into the wound bed, and driving wound contraction. We discover that mechanical stimulation of the skin with ultrasound can overturn healing defects by activating a calcium/CamKinaseII/Tiam1/Rac1 pathway that substitutes for fibronectin-dependent signaling and promotes fibroblast migration. Treatment of diabetic and aged mice recruits fibroblasts to the wound bed and reduces healing times by 30%, restoring healing rates to those observed in young, healthy animals. Ultrasound treatment is equally effective in rescuing the healing defects of animals lacking fibronectin receptors, and can be blocked by pharmacological inhibition of the CamKinaseII pathway. Finally, we discover that the migration defects of fibroblasts from human venous leg ulcer patients can be reversed by ultrasound, demonstrating that the approach is applicable to human chronic samples. By demonstrating that this alternative Rac1 pathway can substitute for that normally operating in the skin, we identify future opportunities for management of chronic wounds.

  15. Reversible dihydrogen activation and hydride transfer by a uranium nitride complex

    Energy Technology Data Exchange (ETDEWEB)

    Falcone, Marta; Poon, Lok Nga; Fadaei Tirani, Farzaneh; Mazzanti, Marinella [Institut des Sciences et Ingenierie Chimiques, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne (Switzerland)

    2018-03-26

    Cleavage of dihydrogen is an important step in the industrial and enzymatic transformation of N{sub 2} into ammonia. The reversible cleavage of dihydrogen was achieved under mild conditions (room temperature and 1 atmosphere of H{sub 2}) by the molecular uranium nitride complex, [Cs{U(OSi(O"tBu)_3)_3}{sub 2}(μ-N)], leading to a rare hydride-imide bridged diuranium(IV) complex, [Cs{U(OSi(O"tBu)_3)_3}{sub 2}(μ-H)(μ-NH)], that slowly releases H{sub 2} under vacuum. This complex is highly reactive and quickly transfers hydride to acetonitrile and carbon dioxide at room temperature, affording the ketimide- and formate-bridged U{sup IV} species [Cs{U(OSi(O"tBu)_3)_3}{sub 2}(μ-NH)(μ-CH{sub 3}CHN)] and [Cs{U(OSi(O"tBu)_3)_3}{sub 2}(μ-HCOO)(μ-NHCOO)]. (copyright 2018 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

  16. Re-activation of degraded nickel cermet anodes - Nano-particle formation via reverse current pulses

    DEFF Research Database (Denmark)

    Hauch, Anne; Marchese, M.; Lanzini, A.

    2018-01-01

    The Ni/yttria-stabilized-zirconia (YSZ) cermet is the most commonly applied fuel electrode for solid oxide cells (SOCs). Loss of Ni/YSZ electrode activity is a key life-time limiting factor of the SOC. Developing means to mitigate this loss of performance or re-activate a fuel electrode is theref......The Ni/yttria-stabilized-zirconia (YSZ) cermet is the most commonly applied fuel electrode for solid oxide cells (SOCs). Loss of Ni/YSZ electrode activity is a key life-time limiting factor of the SOC. Developing means to mitigate this loss of performance or re-activate a fuel electrode...

  17. G3-C12 Peptide Reverses Galectin-3 from Foe to Friend for Active Targeting Cancer Treatment.

    Science.gov (United States)

    Sun, Wei; Li, Lian; Yang, Qingqing; Shan, Wei; Zhang, Zhirong; Huang, Yuan

    2015-11-02

    Galectin-3 is overexpressed by numerous carcinomas and is a potential target for active tumor treatments. On the other hand, galectin-3 also plays a key role in cancer progression and prevents cells from undergoing apoptosis, thereby offsetting the benefits of active targeting drugs. However, the relative contribution of the protective antiapoptotic effects of galectin-3 and the proapoptotic effects of galectin-3-targeted therapies has remained yet unrevealed. Here, we show that a galectin-3-binding peptide G3-C12 could reverse galectin-3 from foe to friend for active targeting delivery system. Results showed G3-C12 modified N-(2-hydroxypropyl)methacrylamide copolymer doxorubicin conjugates (G3-C12-HPMA-Dox) could internalize into galectin-3 overexpressed PC-3 cells via a highly specific ligand-receptor pathway (2.2 times higher cellular internalization than HPMA-Dox). The internalized Dox stimulated the translocation of galectin-3 to the mitochondria to prevent from apoptosis. In turn, this caused G3-C12-HPMA-Dox to concentrate into the mitochondria after binding to galectin-3 intracellularly. Initially, mitochondrial galectin-3 weakened Dox-induced mitochondrial damage; however, as time progressed, G3-C12 active-mediation allowed increasing amounts of Dox to be delivered to the mitochondria, which eventually induced higher level of apoptosis than nontargeted copolymers. In addition, G3-C12 downregulates galectin-3 expression, 0.43 times lower than control cells, which could possibly be responsible for the suppressed cell migration. Thus, G3-C12 peptide exerts sequential targeting to both cell membrane and mitochondria via regulating galectin-3, and eventually reverses and overcomes the protective effects of galectin-3; therefore, it could be a promising agent for the treatment of galectin-3-overexpressing cancers.

  18. Reverse Osmosis

    Indian Academy of Sciences (India)

    many applications, one of which is desalination of seawater. The inaugural Nobel Prize in Chemistry was awarded in 1901 to van 't Hoff for his seminal work in this area. The present article explains the principle of osmosis and reverse osmosis. Osmosis and Reverse Osmosis. As the name suggests, reverse osmosis is the ...

  19. Reversal of diabetic peripheral neuropathy with phototherapy (MIRE) decreases falls and the fear of falling and improves activities of daily living in seniors.

    Science.gov (United States)

    Powell, Mark W; Carnegie, Dale H; Burke, Thomas J

    2006-01-01

    to determine whether restoration of sensation, impaired due to diabetic peripheral neuropathy (DPN), would reduce the number of falls and the fear of falling and improve activities of daily living (ADL) in a Medicare-aged population. retrospective cohort study of patients with documented, monochromatic near-infrared phototherapy (MIRE)-mediated, symptomatic reversal of DPN. responses to a health status questionnaire following symptomatic reversal of DPN. 252 patients (mean age 76 years) provided health information following symptomatic reversal of diabetic neuropathy (mean duration 8.6 months). incidence of falls and fear of falling decreased within 1 month after reversal of peripheral neuropathy and remained low after 1 year. Likewise, improved ADL were evident soon after reversal of peripheral neuropathy and showed further improvement after 1 year. Overall, reversal of peripheral neuropathy in a clinician's office and subsequent use of MIRE at home was associated with a 78% reduction in falls, a 79% decrease in balance-related fear of falling and a 72% increase in ADL (P < 0.0002 for all results). reversal of peripheral neuropathy is associated with an immediate reduction in the absolute number of falls, a reduced fear of falling and improved ADL. These results suggest that symptomatic reversal of diabetic neuropathy will have a substantial favourable, long-term socioeconomic impact on patients with DPN and the Medicare system, and improve the quality of life for elderly patients with diabetes and peripheral neuropathy.

  20. Persulfate Oxidation Regeneration of Granular Activated Carbon: Reversible Impacts on Sorption Behavior

    Science.gov (United States)

    Chemical oxidation regeneration of granular activated carbon (GAC) is a developing technology that can be carried out utilizing thermally-activated persulfate. During chemical regeneration of GAC, aggressive oxidative conditions lead to high acidity (pH < 2) and the accumulation ...

  1. Selective Activation of M4 Muscarinic Acetylcholine Receptors Reverses MK-801-Induced Behavioral Impairments and Enhances Associative Learning in Rodents

    Science.gov (United States)

    2015-01-01

    Positive allosteric modulators (PAMs) of the M4 muscarinic acetylcholine receptor (mAChR) represent a novel approach for the treatment of psychotic symptoms associated with schizophrenia and other neuropsychiatric disorders. We recently reported that the selective M4 PAM VU0152100 produced an antipsychotic drug-like profile in rodents after amphetamine challenge. Previous studies suggest that enhanced cholinergic activity may also improve cognitive function and reverse deficits observed with reduced signaling through the N-methyl-d-aspartate subtype of the glutamate receptor (NMDAR) in the central nervous system. Prior to this study, the M1 mAChR subtype was viewed as the primary candidate for these actions relative to the other mAChR subtypes. Here we describe the discovery of a novel M4 PAM, VU0467154, with enhanced in vitro potency and improved pharmacokinetic properties relative to other M4 PAMs, enabling a more extensive characterization of M4 actions in rodent models. We used VU0467154 to test the hypothesis that selective potentiation of M4 receptor signaling could ameliorate the behavioral, cognitive, and neurochemical impairments induced by the noncompetitive NMDAR antagonist MK-801. VU0467154 produced a robust dose-dependent reversal of MK-801-induced hyperlocomotion and deficits in preclinical models of associative learning and memory functions, including the touchscreen pairwise visual discrimination task in wild-type mice, but failed to reverse these stimulant-induced deficits in M4 KO mice. VU0467154 also enhanced the acquisition of both contextual and cue-mediated fear conditioning when administered alone in wild-type mice. These novel findings suggest that M4 PAMs may provide a strategy for addressing the more complex affective and cognitive disruptions associated with schizophrenia and other neuropsychiatric disorders. PMID:25137629

  2. Opiate-induced suppression of rat hypoglossal motoneuron activity and its reversal by ampakine therapy.

    Directory of Open Access Journals (Sweden)

    Amanda R Lorier

    2010-01-01

    Full Text Available Hypoglossal (XII motoneurons innervate tongue muscles and are vital for maintaining upper-airway patency during inspiration. Depression of XII nerve activity by opioid analgesics is a significant clinical problem, but underlying mechanisms are poorly understood. Currently there are no suitable pharmacological approaches to counter opiate-induced suppression of XII nerve activity while maintaining analgesia. Ampakines accentuate alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA receptor responses. The AMPA family of glutamate receptors mediate excitatory transmission to XII motoneurons. Therefore the objectives were to determine whether the depressant actions of mu-opioid receptor activation on inspiratory activity includes a direct inhibitory action at the inspiratory premotoneuron to XII motoneuron synapse, and to identify underlying mechanism(s. We then examined whether ampakines counteract opioid-induced depression of XII motoneuron activity.A medullary slice preparation from neonatal rat that produces inspiratory-related output in vitro was used. Measurements of inspiratory burst amplitude and frequency were made from XII nerve roots. Whole-cell patch recordings from XII motoneurons were used to measure membrane currents and synaptic events. Application of the mu-opioid receptor agonist, DAMGO, to the XII nucleus depressed the output of inspiratory XII motoneurons via presynaptic inhibition of excitatory glutamatergic transmission. Ampakines (CX614 and CX717 alleviated DAMGO-induced depression of XII MN activity through postsynaptic actions on XII motoneurons.The inspiratory-depressant actions of opioid analgesics include presynaptic inhibition of XII motoneuron output. Ampakines counteract mu-opioid receptor-mediated depression of XII motoneuron inspiratory activity. These results suggest that ampakines may be beneficial in countering opiate-induced suppression of XII motoneuron activity and resultant impairment of airway patency.

  3. Reversible Redox Activity by Ion-pH Dually Modulated Duplex Formation of i-Motif DNA with Complementary G-DNA

    Directory of Open Access Journals (Sweden)

    Soyoung Chang

    2018-04-01

    Full Text Available The unique biological features of supramolecular DNA have led to an increasing interest in biomedical applications such as biosensors. We have developed an i-motif and G-rich DNA conjugated single-walled carbon nanotube hybrid materials, which shows reversible conformational switching upon external stimuli such as pH (5 and 8 and presence of ions (Li+ and K+. We observed reversible electrochemical redox activity upon external stimuli in a quick and robust manner. Given the ease and the robustness of this method, we believe that pH- and ion-driven reversible DNA structure transformations will be utilized for future applications for developing novel biosensors.

  4. Self-assembled air-stable magnesium hydride embedded in 3-D activated carbon for reversible hydrogen storage.

    Science.gov (United States)

    Shinde, S S; Kim, Dong-Hyung; Yu, Jin-Young; Lee, Jung-Ho

    2017-06-01

    The rational design of stable, inexpensive catalysts with excellent hydrogen dynamics and sorption characteristics under realistic environments for reversible hydrogen storage remains a great challenge. Here, we present a simple and scalable strategy to fabricate a monodispersed, air-stable, magnesium hydride embedded in three-dimensional activated carbon with periodic synchronization of transition metals (MHCH). The high surface area, homogeneous distribution of MgH 2 nanoparticles, excellent thermal stability, high energy density, steric confinement by carbon, and robust architecture of the catalyst resulted in a noticeable enhancement of the hydrogen storage performance. The resulting MHCH-5 exhibited outstanding hydrogen storage performance, better than that of most reported Mg-based hydrides, with a high storage density of 6.63 wt% H 2 , a rapid kinetics loading in hydrogenation compared to that of commercial MgH 2 . The origin of the intrinsic hydrogen thermodynamics was elucidated via solid state 1 H NMR. This work presents a readily scaled-up strategy towards the design of realistic catalysts with superior functionality and stability for applications in reversible hydrogen storage, lithium ion batteries, and fuel cells.

  5. Fast, non-competitive and reversible inhibition of NMDA-activated currents by 2-BFI confers neuroprotection.

    Directory of Open Access Journals (Sweden)

    Zhao Han

    Full Text Available Excessive activation of the N-methyl-D-aspartic acid (NMDA type glutamate receptors (NMDARs causes excitotoxicity, a process important in stroke-induced neuronal death. Drugs that inhibit NMDA receptor-mediated [Ca(2+]i influx are potential leads for development to treat excitotoxicity-induced brain damage. Our previous studies showed that 2-(2-benzofu-ranyl-2-imidazoline (2-BFI, an immidazoline receptor ligand, dose-dependently protects rodent brains from cerebral ischemia injury. However, the molecular mechanisms remain unclear. In this study, we found that 2-BFI transiently and reversibly inhibits NMDA, but not AMPA currents, in a dose-dependent manner in cultured rat cortical neurons. The mechanism of 2-BFI inhibition of NMDAR is through a noncompetitive fashion with a faster on (Kon = 2.19±0.33×10(-9 M(-1 sec(-1 and off rate (Koff = 0.67±0.02 sec(-1 than those of memantine, a gold standard for therapeutic inhibition NMDAR-induced excitotoxicity. 2-BFI also transiently and reversibly blocked NMDA receptor-mediated calcium entry to cultured neurons and provided long-term neuroprotection against NMDA toxicity in vitro. Collectively, these studies demonstrated a potential mechanism of 2-BFI-mediated neuroprotection and indicated that 2-BFI is an excellent candidate for repositioning as a drug for stroke treatment.

  6. Quantification of functional groups and modeling of their ionization behavior in the active layer of FT30 reverse osmosis membrane.

    Science.gov (United States)

    Coronell, Orlando; Mariñas, Benito J; Zhang, Xijing; Cahill, David G

    2008-07-15

    A new experimental approach was developed to measure the concentration of charged functional groups (FGs) in the active layer of thin-film composite reverse osmosis (RO) and nanofiltration (NF) membranes as a function of solution pH. FT30 RO membrane, with a fully aromatic polyamide (PA) active layer sandwiched between a polysulfone support and a coating layer, was used. The experiments consisted of saturating charged FGs with heavy ion probes, and determining the ion probe concentration by Rutherford backscattering spectrometry (RBS). Deprotonated carboxylic groups were saturated with Ag+, and protonated amine groups with W04(2-). The ionization behavior of carboxylic and amine groups was modeled based on acid-base equilibrium theory. While the ionization behavior of amine groups was satisfactorily described by one dissociation constant (pKa = 4.74), two pKa values (5.23 and 8.97) were necessary to describe the titration curve of carboxylic groups. These results were consistent with the bimodal pore size distribution (PSD) of FT30 active layer reported in the literature. The calculated total concentrations of carboxylic and amine groups in the active layer of the FT30 RO membrane studied were 0.432 and 0.036 M, respectively, and the isoelectric point (IEP) was 4.7. The total concentration of carboxylic and amine groups revealed that the degree of cross-linking of the PA active layer of the FT30 RO membrane studied was 94%.

  7. Reverse Message-Framing Effects on Accelerometer-Assessed Physical Activity Among Older Outpatients With Type 2 Diabetes.

    Science.gov (United States)

    Li, Kin-Kit; Ng, Lorna; Cheng, Sheung-Tak; Fung, Helene H

    2017-06-01

    It has been suggested that gain-framed messages are more effective than loss-framed messages in promoting low-risk health behaviors such as physical activity. Because of a heightened health concern and possible medical complications, older adults with type 2 diabetes (T2D) may consider physical activity to be risky. This study examined whether a reverse message-framing effect would be found among older adults with T2D. The participants included 211 sedentary and older adults with T2D recruited from an outpatient clinic. The participants were randomly assigned to receive either gain-framed or loss-framed messages and wore an accelerometer to monitor their physical activity for 2 weeks. The participants who received loss-framed messages were more physically active than those who received gain-framed messages (β = 0.13, p = .033). This loss-frame advantage might be attributable to the heightened perceived risks among older outpatients with T2D and the temporarily activated prevention-focused orientation in a clinical setting.

  8. Radiochemical assay for determination of dihydropyrimidinase activity using reversed-phase high-performance liquid chromatography

    NARCIS (Netherlands)

    van Kuilenburg, A. B.; van Lenthe, H.; van Gennip, A. H.

    1999-01-01

    A radiochemical assay was developed to measure the activity of dihydropyrimidinase (DHP) in human liver homogenates. The method is based on the separation of radiolabeled dihydrouracil from N-carbamyl-beta-alanine by HPLC with on-line detection of radioactivity combined with detection of 14CO2 by

  9. Reversing Implicit Gender Stereotype Activation as a Function of Exposure to Traditional Gender Roles

    NARCIS (Netherlands)

    de Lemus, Soledad; Spears, Russell; Bukowski, Marcin; Moya, Miguel; Lupianez, Juan

    2013-01-01

    We examined the influence of exposure to traditional gender roles on the activation of gender stereotypes in Spanish women. An associative procedure was used to expose participants to stereotypical vs. counterstereotypical gender roles, and a word categorization task with stereotypically feminine

  10. Reversible control of kinesin activity and microtubule gliding speeds by switching the doping states of a conducting polymer support

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Brett D [US Naval Research Laboratory, Code 6930, Washington, DC 20375 (United States); Velea, Luminita M [US Naval Research Laboratory, Code 6930, Washington, DC 20375 (United States); Soto, Carissa M [US Naval Research Laboratory, Code 6930, Washington, DC 20375 (United States); Whitaker, Craig M [US Naval Academy, Department of Chemistry, Annapolis, MD 21402 (United States); Gaber, Bruce P [US Naval Research Laboratory, Code 6930, Washington, DC 20375 (United States); Ratna, Banahalli [US Naval Research Laboratory, Code 6930, Washington, DC 20375 (United States)

    2007-02-07

    We describe a method for reversibly controlling the ATPase activity of streptavidin-linked kinesin by changing the doping states of a conducting polymer support. When the polymer (poly(CH{sub 2}OH-EDOT)) was electrochemically switched from its dedoped (semiconducting) state to its doped (conducting) state, the ATPase activity of the adsorbed kinesin complex decreased by 35% with a concomitant decrease in the gliding speeds of kinesin-driven microtubules. When the polymer was switched back to its original dedoped state, nearly identical increases were observed in the kinesin ATPase activity and microtubule speeds. Use of a fluorescent ATP substrate analogue showed that the total amount of kinesin adsorbed on the poly(CH{sub 2}OH-EDOT) surface remained constant as the doping state of the polymer was switched. The microtubules exhibited nearly identical speed differences on the doped and dedoped surfaces for both chemical and electrochemical doping methods. Michaelis-Menten modelling suggests that the doped surface acts as an 'uncompetitive inhibitor' of kinesin. This work represents an investigation into the phenomenon of an electrically switchable surface exerting a moderating effect on the activity of an adsorbed protein that does not contain a bound, electroactive metal ion.

  11. The brown algae Pl.LSU/2 group II intron-encoded protein has functional reverse transcriptase and maturase activities.

    Directory of Open Access Journals (Sweden)

    Madeleine Zerbato

    Full Text Available Group II introns are self-splicing mobile elements found in prokaryotes and eukaryotic organelles. These introns propagate by homing into precise genomic locations, following assembly of a ribonucleoprotein complex containing the intron-encoded protein (IEP and the spliced intron RNA. Engineered group II introns are now commonly used tools for targeted genomic modifications in prokaryotes but not in eukaryotes. We speculate that the catalytic activation of currently known group II introns is limited in eukaryotic cells. The brown algae Pylaiella littoralis Pl.LSU/2 group II intron is uniquely capable of in vitro ribozyme activity at physiological level of magnesium but this intron remains poorly characterized. We purified and characterized recombinant Pl.LSU/2 IEP. Unlike most IEPs, Pl.LSU/2 IEP displayed a reverse transcriptase activity without intronic RNA. The Pl.LSU/2 intron could be engineered to splice accurately in Saccharomyces cerevisiae and splicing efficiency was increased by the maturase activity of the IEP. However, spliced transcripts were not expressed. Furthermore, intron splicing was not detected in human cells. While further tool development is needed, these data provide the first functional characterization of the PI.LSU/2 IEP and the first evidence that the Pl.LSU/2 group II intron splicing occurs in vivo in eukaryotes in an IEP-dependent manner.

  12. Phosphatidylcholine Reverses Ethanol-Induced Increase in Transepithelial Endotoxin Permeability and Abolishes Transepithelial Leukocyte Activation

    DEFF Research Database (Denmark)

    Mitzscherling, Katja; Volynets, Valentina; Parlesak, Alexandr

    2009-01-01

    Chronic alcohol abuse increases both intestinal bacterial overgrowth and intestinal permeability to macromolecules. Intestinal permeability of endotoxin, a component of the outer cell membrane of Gram-negative bacteria, plays a crucial role in the development of alcohol-induced liver disease (ALD......). As impaired bile flow leads to endotoxemia and the bile component phosphatidylcholine (PC) is therapeutically active in ALD, we tested the hypothesis that conjugated primary bile salts (CPBS) and PC inhibit ethanol-enhanced transepithelial permeability of endotoxin and the subsequent transepithelial...... activation of human leukocytes. For this purpose, we used a model in which intestinal epithelial cells (Caco-2) were basolaterally cocultivated with mononuclear leukocytes. Cells were challenged apically with endotoxin from Escherichia coli K12 and were incubated with or without the addition of CPBS (1.5 m...

  13. Phosphatidylcholine reverses ethanol-induced increase in transepithelial endotoxin permeability and abolishes transepithelial leukocyte activation

    DEFF Research Database (Denmark)

    Mitscherling, K.; Volynets, V.; Parlesak, Alexandr

    2009-01-01

    BACKGROUND: Chronic alcohol abuse increases both intestinal bacterial overgrowth and intestinal permeability to macromolecules. Intestinal permeability of endotoxin, a component of the outer cell membrane of Gram-negative bacteria, plays a crucial role in the development of alcohol-induced liver...... disease (ALD). As impaired bile flow leads to endotoxemia and the bile component phosphatidylcholine (PC) is therapeutically active in ALD, we tested the hypothesis that conjugated primary bile salts (CPBS) and PC inhibit ethanol-enhanced transepithelial permeability of endotoxin and the subsequent...... transepithelial activation of human leukocytes. METHODS: For this purpose, we used a model in which intestinal epithelial cells (Caco-2) were basolaterally cocultivated with mononuclear leukocytes. Cells were challenged apically with endotoxin from Escherichia coli K12 and were incubated with or without...

  14. Chemogenetic activation of the lateral hypothalamus reverses early life stress-induced deficits in motivational drive.

    Science.gov (United States)

    Campbell, Erin J; Mitchell, Caitlin S; Adams, Cameron D; Yeoh, Jiann Wei; Hodgson, Deborah M; Graham, Brett A; Dayas, Christopher V

    2017-10-01

    Altered motivated behaviour is a cardinal feature of several neuropsychiatric conditions including mood disorders. One well-characterized antecedent to the development of mood disorders is exposure to early life stress (ELS). A key brain substrate controlling motivated behaviour is the lateral hypothalamus (LH). Here, we examined the effect of ELS on LH activation and the motivation to self-administer sucrose. We tested whether chemogenetic activation of LH circuits could modify sucrose responding in ELS rats and examined the impact on LH cell populations. Male rat pups were maternally separated for 0 or 3 h on postnatal days 2-14. During adolescence, rats received bilateral injections of hM3D(Gq), the excitatory designer receptor exclusively activated by designer drugs, into LH. In adulthood, rats were trained to self-administer sucrose and tested under a progressive ratio schedule to determine their motivation for reward following injection with either vehicle or 5 mg/kg clozapine-N-oxide. Brains were processed for Fos-protein immunohistochemistry. ELS significantly suppressed lever responding for sucrose, indicating a long-lasting impact of ELS on motivation circuits. hM3D(Gq) activation of LH increased responding, normalizing deficits in ELS rats, and increased Fos-positive orexin and MCH cell numbers within LH. Our findings indicate that despite being susceptible to environmental stressors, LH circuits retain the capacity to overcome ELS-induced deficits in motivated behaviour. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  15. Muscle atrophy reversed by growth factor activation of satellite cells in a mouse muscle atrophy model.

    Directory of Open Access Journals (Sweden)

    Simon Hauerslev

    Full Text Available Muscular dystrophies comprise a large group of inherited disorders that lead to progressive muscle wasting. We wanted to investigate if targeting satellite cells can enhance muscle regeneration and thus increase muscle mass. We treated mice with hepatocyte growth factor and leukemia inhibitory factor under three conditions: normoxia, hypoxia and during myostatin deficiency. We found that hepatocyte growth factor treatment led to activation of the Akt/mTOR/p70S6K protein synthesis pathway, up-regulation of the myognic transcription factors MyoD and myogenin, and subsequently the negative growth control factor, myostatin and atrophy markers MAFbx and MuRF1. Hypoxia-induced atrophy was partially restored by hepatocyte growth factor combined with leukemia inhibitory factor treatment. Dividing satellite cells were three-fold increased in the treatment group compared to control. Finally, we demonstrated that myostatin regulates satellite cell activation and myogenesis in vivo following treatment, consistent with previous findings in vitro. Our results suggest, not only a novel in vivo pharmacological treatment directed specifically at activating the satellite cells, but also a myostatin dependent mechanism that may contribute to the progressive muscle wasting seen in severely affected patients with muscular dystrophy and significant on-going regeneration. This treatment could potentially be applied to many conditions that feature muscle wasting to increase muscle bulk and strength.

  16. Super-resolution binding activated localization microscopy through reversible change of DNA conformation.

    Science.gov (United States)

    Szczurek, Aleksander; Birk, Udo; Knecht, Hans; Dobrucki, Jurek; Mai, Sabine; Cremer, Christoph

    2018-01-01

    Methods of super-resolving light microscopy (SRM) have found an exponentially growing range of applications in cell biology, including nuclear structure analyses. Recent developments have proven that Single Molecule Localization Microscopy (SMLM), a type of SRM, is particularly useful for enhanced spatial analysis of the cell nucleus due to its highest resolving capability combined with very specific fluorescent labeling. In this commentary we offer a brief review of the latest methodological development in the field of SMLM of chromatin designated DNA Structure Fluctuation Assisted Binding Activated Localization Microscopy (abbreviated as fBALM) as well as its potential future applications in biology and medicine.

  17. Radiation-induced progressive decreasing in the expression of reverse transcriptase gene of hEST2 and telomerase activity

    International Nuclear Information System (INIS)

    Zhu Hanneng; Chen Wenying; Xiong Sidong

    2000-01-01

    Telomerase is a ribonucleoprotein complex that adds heximeric repeats called telomeres to the growing ends of chromosomal DNA. Telomerase activity is present in a vast majority of tumors but is repressed in most normal tissues. Human telomerase catalytic subunit gene (hEST2) reverse transcriptase (RT) segment was cloned by PCR according to the sequence published in GeneBank. PCR was used to investigate the expression of the hEST2 RT segment in diverse tumors as well as in various normal tissues. Results indicated that hEST2 RT segment was detectable in tumor cells lines but not in normal cells and tissues. In order to identify the relationship between telomerase and the biological effect of radiation injury, HeLa cells, KB cells and A431 cells were employed to measure the change in telomerase activity after 60 Co-ray irradiation at RNA level and protein level. Quantitative PCR determined that expression of hEST2 RT segment that encodes seven motifs of the human telomeras decreased with increasing dosage of radiation. In addition, a PCR-based telomeric repeat amplification protocol was used to assay telomerase activity after exposure to radiation. The results strongly support the experiments we had made: Telomerase activity decreases with increasing dosage of radiation. We conclude that detection of the hEST2 RT segment by Northern blotting is a new method for detecting telomerase activity. Furthermore, radiation can cause a dose-dependent decrease in telomerase activity. The effect of radiation on telomerase is one possible reason for the death of cancer cells after irradiation. (author)

  18. Physiological Measures of Dopaminergic and Noradrenergic Activity During Attentional Set Shifting and Reversal

    Directory of Open Access Journals (Sweden)

    Péter Pajkossy

    2018-04-01

    Full Text Available Dopamine (DA and noradrenaline (NA are important neurotransmitters, which are suggested to play a vital role in modulating the neural circuitry involved in the executive control of cognition. One way to investigate the functions of these neurotransmitter systems is to assess physiological indices of DA and NA transmission. Here we examined how variations of spontaneous eye-blink rate and pupil size, as indirect measures of DA and NA activity, respectively, are related to performance in a hallmark aspect of executive control: attentional set shifting. We used the Intra/Extradimensional Set Shifting Task, where participants have to choose between different compound stimuli while the stimulus-reward contingencies change periodically. During such rule shifts, participants have to refresh their attentional set while they reassess which stimulus-features are relevant. We found that both eye-blink rate (EBR and pupil size increased after rule shifts, when explorative processes are required to establish stimulus–reward contingencies. Furthermore, baseline pupil size was related to performance during the most difficult, extradimensional set shifting stage, whereas baseline EBR was associated with task performance prior to this stage. Our results support a range of neurobiological models suggesting that the activity of DA and NA neurotransmitter systems determines individual differences in executive functions (EF, possibly by regulating neurotransmission in prefrontal circuits. We also suggest that assessing specific, easily accessible indirect physiological markers, such as pupil size and blink rate, contributes to the comprehension of the relationship between neurotransmitter systems and EF.

  19. An Evaluation of Active Learning Causal Discovery Methods for Reverse-Engineering Local Causal Pathways of Gene Regulation

    Science.gov (United States)

    Ma, Sisi; Kemmeren, Patrick; Aliferis, Constantin F.; Statnikov, Alexander

    2016-01-01

    Reverse-engineering of causal pathways that implicate diseases and vital cellular functions is a fundamental problem in biomedicine. Discovery of the local causal pathway of a target variable (that consists of its direct causes and direct effects) is essential for effective intervention and can facilitate accurate diagnosis and prognosis. Recent research has provided several active learning methods that can leverage passively observed high-throughput data to draft causal pathways and then refine the inferred relations with a limited number of experiments. The current study provides a comprehensive evaluation of the performance of active learning methods for local causal pathway discovery in real biological data. Specifically, 54 active learning methods/variants from 3 families of algorithms were applied for local causal pathways reconstruction of gene regulation for 5 transcription factors in S. cerevisiae. Four aspects of the methods’ performance were assessed, including adjacency discovery quality, edge orientation accuracy, complete pathway discovery quality, and experimental cost. The results of this study show that some methods provide significant performance benefits over others and therefore should be routinely used for local causal pathway discovery tasks. This study also demonstrates the feasibility of local causal pathway reconstruction in real biological systems with significant quality and low experimental cost. PMID:26939894

  20. Muscle Atrophy Reversed by Growth Factor Activation of Satellite Cells in a Mouse Muscle Atrophy Model

    DEFF Research Database (Denmark)

    Hauerslev, Simon; Vissing, John; Krag, Thomas O

    2014-01-01

    mechanism that may contribute to the progressive muscle wasting seen in severely affected patients with muscular dystrophy and significant on-going regeneration. This treatment could potentially be applied to many conditions that feature muscle wasting to increase muscle bulk and strength.......Muscular dystrophies comprise a large group of inherited disorders that lead to progressive muscle wasting. We wanted to investigate if targeting satellite cells can enhance muscle regeneration and thus increase muscle mass. We treated mice with hepatocyte growth factor and leukemia inhibitory...... factor under three conditions: normoxia, hypoxia and during myostatin deficiency. We found that hepatocyte growth factor treatment led to activation of the Akt/mTOR/p70S6K protein synthesis pathway, up-regulation of the myognic transcription factors MyoD and myogenin, and subsequently the negative growth...

  1. Ibuprofen arginate retains eNOS substrate activity and reverses endothelial dysfunction: implications for the COX-2/ADMA axis.

    Science.gov (United States)

    Kirkby, Nicholas S; Tesfai, Abel; Ahmetaj-Shala, Blerina; Gashaw, Hime H; Sampaio, Walkyria; Etelvino, Gisele; Leão, Nádia Miricéia; Santos, Robson A; Mitchell, Jane A

    2016-12-01

    Nonsteroidal antiinflammatory drugs, including ibuprofen, are among the most commonly used medications and produce their antiinflammatory effects by blocking cyclooxygenase (COX)-2. Their use is associated with increased risk of heart attacks caused by blocking COX-2 in the vasculature and/or kidney, with our recent work implicating the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA), a cardiotoxic hormone whose effects can be prevented by l-arginine. The ibuprofen salt ibuprofen arginate (Spididol) was created to increase solubility but we suggest that it could also augment the NO pathway through codelivery of arginine. Here we investigated the idea that ibuprofen arginate can act to simultaneously inhibit COX-2 and preserve the NO pathway. Ibuprofen arginate functioned similarly to ibuprofen sodium for inhibition of mouse/human COX-2, but only ibuprofen arginate served as a substrate for NOS. Ibuprofen arginate but not ibuprofen sodium also reversed the inhibitory effects of ADMA and N G -nitro-l-arginine methyl ester on inducible NOS (macrophages) and endothelial NOS in vitro (aorta) and in vivo (blood pressure). These observations show that ibuprofen arginate provides, in one preparation, a COX-2 inhibitor and NOS substrate that could act to negate the harmful cardiovascular consequences mediated by blocking renal COX-2 and increased ADMA. While remarkably simple, our findings are potentially game-changing in the nonsteroidal antiinflammatory drug arena.-Kirkby, N. S., Tesfai, A., Ahmetaj-Shala, B., Gashaw, H. H., Sampaio, W., Etelvino, G., Leão, N. M., Santos, R. A., Mitchell, J. A. Ibuprofen arginate retains eNOS substrate activity and reverses endothelial dysfunction: implications for the COX-2/ADMA axis. © The Author(s).

  2. The CD8+ memory T-cell state of readiness is actively maintained and reversible

    Science.gov (United States)

    Allam, Atef; Conze, Dietrich B.; Giardino Torchia, Maria Letizia; Munitic, Ivana; Yagita, Hideo; Sowell, Ryan T.; Marzo, Amanda L.

    2009-01-01

    The ability of the adaptive immune system to respond rapidly and robustly upon repeated antigen exposure is known as immunologic memory, and it is thought that acquisition of memory T-cell function is an irreversible differentiation event. In this study, we report that many phenotypic and functional characteristics of antigen-specific CD8 memory T cells are lost when they are deprived of contact with dendritic cells. Under these circumstances, memory T cells reverted from G1 to the G0 cell-cycle state and responded to stimulation like naive T cells, as assessed by proliferation, dependence upon costimulation, and interferon-γ production, without losing cell surface markers associated with memory. The memory state was maintained by signaling via members of the tumor necrosis factor receptor superfamily, CD27 and 4-1BB. Foxo1, a transcription factor involved in T-cell quiescence, was reduced in memory cells, and stimulation of naive CD8 cells via CD27 caused Foxo1 to be phosphorylated and emigrate from the nucleus in a phosphatidylinositol-3 kinase–dependent manner. Consistent with these results, maintenance of G1 in vivo was compromised in antigen-specific memory T cells in vesicular stomatitis virus-infected CD27-deficient mice. Therefore, sustaining the functional phenotype of T memory cells requires active signaling and maintenance. PMID:19617575

  3. Lipeo-sCT: a novel reversible lipidized salmon calcitonin derivative, its biophysical properties and hypocalcemic activity.

    Science.gov (United States)

    Cheng, Weiqiang; Lim, Lee-Yong

    2009-05-12

    We have previously described the design and synthesis of Mal-sCT and compared its biological activity with its reversible counterpart, REAL-sCT. Mal-sCT was salmon calcitonin (sCT) conjugated with two molecules of an epsilon-maleimido lysine derivative of palmitic acid via non-reversible thioether bonds at its cysteine residues while REAL-sCT was sCT conjugated with two molecules of a cysteine derivative of palmitic acid via reducible disulfide bonds at its cysteine residues. Neither compounds when dissolved in water could reproducibly improved the oral deliverability of sCT. The purpose of this study was to characterize and evaluate Lipeo-sCT, a novel sCT analog conjugated via reducible disulfide bonds with two amphiphilic groups consisting of a hydrophobic hexadecyl moiety attached via an ether bond to a hydrophilic triethylene glycol moiety. Lipeo-sCT was successfully synthesized by a 4-step reaction, purified and identified by ESI-MS. Analysis by dynamic light scattering (DLS) and transmission electron microscopy (TEM) suggested it had a propensity to form aggregates in water, although the aggregation behavior was controllable by modulating solvent polarity. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay indicated a lack of cytotoxicity against the Caco-2 cells at up to 100 microM. Compared with sCT, Lipeo-sCT lowered plasma calcium to comparable levels when injected subcutaneously at 0.15 mg/kg into female Wistar rats, but the hypocalcemic activity of Lipeo-sCT was prolonged by at least 6 more hours. This was attributable to a continual regeneration of sCT from Lipeo-sCT. sCT was detectable in plasma 8h following subcutaneous injection of Lipeo-sCT (1.90 mg/kg), while Lipeo-sCT was not observed in plasma at all time points. By comparison, sCT was detectable in plasma for less than 2.5h following subcutaneous injection at an equivalent dose (1.50mg/kg). Data from this study complement those of previous studies, and add to the body of

  4. Phase reversal of biomechanical functions and muscle activity in backward pedaling.

    Science.gov (United States)

    Ting, L H; Kautz, S A; Brown, D A; Zajac, F E

    1999-02-01

    Computer simulations of pedaling have shown that a wide range of pedaling tasks can be performed if each limb has the capability of executing six biomechanical functions, which are arranged into three pairs of alternating antagonistic functions. An Ext/Flex pair accelerates the limb into extension or flexion, a Plant/Dorsi pair accelerates the foot into plantarflexion or dorsiflexion, and an Ant/Post pair accelerates the foot anteriorly or posteriorly relative to the pelvis. Because each biomechanical function (i.e., Ext, Flex, Plant, Dorsi, Ant, or Post) contributes to crank propulsion during a specific region in the cycle, phasing of a muscle is hypothesized to be a consequence of its ability to contribute to one or more of the biomechanical functions. Analysis of electromyogram (EMG) patterns has shown that this biomechanical framework assists in the interpretation of muscle activity in healthy and hemiparetic subjects during forward pedaling. Simulations show that backward pedaling can be produced with a phase shift of 180 degrees in the Ant/Post pair. No phase shifts in the Ext/Flex and Plant/Dorsi pairs are then necessary. To further test whether this simple yet biomechanically viable strategy may be used by the nervous system, EMGs from 7 muscles in 16 subjects were measured during backward as well as forward pedaling. As predicted, phasing in vastus medialis (VM), tibialis anterior (TA), medial gastrocnemius (MG), and soleus (SL) were unaffected by pedaling direction, with VM and SL contributing to Ext, MG to Plant, and TA to Dorsi. In contrast, phasing in biceps femoris (BF) and semimembranosus (SM) were affected by pedaling direction, as predicted, compatible with their contribution to the directionally sensitive Post function. Phasing of rectus femoris (RF) was also affected by pedaling direction; however, its ability to contribute to the directionally sensitive Ant function may only be expressed in forward pedaling. RF also contributed significantly to

  5. Ethanol and anaerobic conditions reversibly inhibit commercial cellulase activity in thermophilic simultaneous saccharification and fermentation (tSSF

    Directory of Open Access Journals (Sweden)

    Podkaminer Kara K

    2012-06-01

    Full Text Available Abstract Background A previously developed mathematical model of low solids thermophilic simultaneous saccharification and fermentation (tSSF with Avicel was unable to predict performance at high solids using a commercial cellulase preparation (Spezyme CP and the high ethanol yield Thermoanaerobacterium saccharolyticum strain ALK2. The observed hydrolysis proceeded more slowly than predicted at solids concentrations greater than 50 g/L Avicel. Factors responsible for this inaccuracy were investigated in this study. Results Ethanol dramatically reduced cellulase activity in tSSF. At an Avicel concentration of 20 g/L, the addition of ethanol decreased conversion at 96 hours, from 75% in the absence of added ethanol down to 32% with the addition of 34 g/L initial ethanol. This decrease is much greater than expected based on hydrolysis inhibition results in the absence of a fermenting organism. The enhanced effects of ethanol were attributed to the reduced, anaerobic conditions of tSSF, which were shown to inhibit cellulase activity relative to hydrolysis under aerobic conditions. Cellulose hydrolysis in anaerobic conditions was roughly 30% slower than in the presence of air. However, this anaerobic inhibition was reversed by exposing the cellulase enzymes to air. Conclusion This work demonstrates a previously unrecognized incompatibility of enzymes secreted by an aerobic fungus with the fermentation conditions of an anaerobic bacterium and suggests that enzymes better suited to industrially relevant fermentation conditions would be valuable. The effects observed may be due to inactivation or starvation of oxygen dependent GH61 activity, and manipulation or replacement of this activity may provide an opportunity to improve biomass to fuel process efficiency.

  6. Entropy Production in Field Theories without Time-Reversal Symmetry: Quantifying the Non-Equilibrium Character of Active Matter

    Directory of Open Access Journals (Sweden)

    Cesare Nardini

    2017-04-01

    Full Text Available Active-matter systems operate far from equilibrium because of the continuous energy injection at the scale of constituent particles. At larger scales, described by coarse-grained models, the global entropy production rate S quantifies the probability ratio of forward and reversed dynamics and hence the importance of irreversibility at such scales: It vanishes whenever the coarse-grained dynamics of the active system reduces to that of an effective equilibrium model. We evaluate S for a class of scalar stochastic field theories describing the coarse-grained density of self-propelled particles without alignment interactions, capturing such key phenomena as motility-induced phase separation. We show how the entropy production can be decomposed locally (in real space or spectrally (in Fourier space, allowing detailed examination of the spatial structure and correlations that underly departures from equilibrium. For phase-separated systems, the local entropy production is concentrated mainly on interfaces, with a bulk contribution that tends to zero in the weak-noise limit. In homogeneous states, we find a generalized Harada-Sasa relation that directly expresses the entropy production in terms of the wave-vector-dependent deviation from the fluctuation-dissipation relation between response functions and correlators. We discuss extensions to the case where the particle density is coupled to a momentum-conserving solvent and to situations where the particle current, rather than the density, should be chosen as the dynamical field. We expect the new conceptual tools developed here to be broadly useful in the context of active matter, allowing one to distinguish when and where activity plays an essential role in the dynamics.

  7. Reversed synaptic effects of hypocretin and NPY mediated by excitatory GABA-dependent synaptic activity in developing MCH neurons.

    Science.gov (United States)

    Li, Ying; Xu, Youfen; van den Pol, Anthony N

    2013-03-01

    In mature neurons, GABA is the primary inhibitory neurotransmitter. In contrast, in developing neurons, GABA exerts excitatory actions, and in some neurons GABA-mediated excitatory synaptic activity is more prevalent than glutamate-mediated excitation. Hypothalamic neuropeptides that modulate cognitive arousal and energy homeostasis, hypocretin/orexin and neuropeptide Y (NPY), evoked reversed effects on synaptic actions that were dependent on presynaptic GABA release onto melanin-concentrating hormone (MCH) neurons. MCH neurons were identified by selective green fluorescent protein (GFP) expression in transgenic mice. In adults, hypocretin increased GABA release leading to reduced excitation. In contrast, in the developing brain as studied here with analysis of miniature excitatory postsynaptic currents, paired-pulse ratios, and evoked potentials, hypocretin acted presynaptically to enhance the excitatory actions of GABA. The ability of hypocretin to enhance GABA release increases inhibition in adult neurons but paradoxically enhances excitation in developing MCH neurons. In contrast, NPY attenuation of GABA release reduced inhibition in mature neurons but enhanced inhibition during development by attenuating GABA excitation. Both hypocretin and NPY also evoked direct actions on developing MCH neurons. Hypocretin excited MCH cells by activating a sodium-calcium exchanger and by reducing potassium currents; NPY reduced activity by increasing an inwardly rectifying potassium current. These data for the first time show that both hypocretin and NPY receptors are functional presynaptically during early postnatal hypothalamic development and that both neuropeptides modulate GABA actions during development with a valence of enhanced excitation or inhibition opposite to that of the adult state, potentially allowing neuropeptide modulation of use-dependent synapse stabilization.

  8. Determination of Diffusion Coefficients and Activation Energy of Selected Organic Liquids using Reversed-Flow Gas Chromatographic Technique

    International Nuclear Information System (INIS)

    Khalisanni Khalid; Rashid Atta Khan; Sharifuddin Mohd Zain

    2012-01-01

    Evaporation of vaporize organic liquid has ecological consequences when the compounds are introduced into both freshwater and marine environments through industrial effluents, or introduced directly into the air from industrial unit processes such as bioreactors and cooling towers. In such cases, a rapid and simple method are needed to measure physicochemical properties of the organic liquids. The Reversed-Flow Gas Chromatography (RF-GC) sampling technique is an easy, fast and accurate procedure. It was used to measure the diffusion coefficients of vapors from liquid into a carrier gas and at the same time to determine the rate coefficients for the evaporation of the respective liquid. The mathematical expression describing the elution curves of the samples peaks was derived and used to calculate the respective parameters for the selected liquid pollutants selected such as methanol, ethanol, 1-propanol, 1-butanol, n-pentane, n-hexane, n-heptane and n-hexadecane, evaporating into the carrier gas of nitrogen. The values of diffusion coefficients found were compared with those calculated theoretically or reported in the literature. The values of evaporation rate were used to determine the activation energy of respective samples using Arrhenius equation. An interesting finding of this work is by using an alternative mathematical analysis based on equilibrium at the liquid-gas interphase, the comparison leads to profound agreement between theoretical values of diffusion coefficients and experimental evidence. (author)

  9. Hippocampal theta activity is selectively associated with contingency detection but not discrimination in rabbit discrimination-reversal eyeblink conditioning.

    Science.gov (United States)

    Nokia, Miriam S; Wikgren, Jan

    2010-04-01

    The relative power of the hippocampal theta-band ( approximately 6 Hz) activity (theta ratio) is thought to reflect a distinct neural state and has been shown to affect learning rate in classical eyeblink conditioning in rabbits. We sought to determine if the theta ratio is mostly related to the detection of the contingency between the stimuli used in conditioning or also to the learning of more complex inhibitory associations when a highly demanding delay discrimination-reversal eyeblink conditioning paradigm is used. A high hippocampal theta ratio was not only associated with a fast increase in conditioned responding in general but also correlated with slow emergence of discriminative responding due to sustained responding to the conditioned stimulus not paired with an unconditioned stimulus. The results indicate that the neural state reflected by the hippocampal theta ratio is specifically linked to forming associations between stimuli rather than to the learning of inhibitory associations needed for successful discrimination. This is in line with the view that the hippocampus is responsible for contingency detection in the early phase of learning in eyeblink conditioning. (c) 2009 Wiley-Liss, Inc.

  10. Subfailure overstretch injury leads to reversible functional impairment and purinergic P2X7 receptor activation in intact vascular tissue

    Directory of Open Access Journals (Sweden)

    Weifeng Luo

    2016-09-01

    Full Text Available Vascular stretch injury is associated with blunt trauma, vascular surgical procedures, and harvest of human saphenous vein for use in vascular bypass grafting. A model of subfailure overstretch in rat abdominal aorta was developed to characterize surgical vascular stretch injury. Longitudinal stretch of rat aorta was characterized ex vivo. Stretch to the haptic endpoint where the tissues would no longer lengthen, occurred at twice the resting length. The stress produced at this length was greater than physiologic mechanical forces but well below the level of mechanical disruption. Functional responses were determined in a muscle bath and this subfailure overstretch injury led to impaired smooth muscle function that was partially reversed by treatment with purinergic receptor (P2X7R antagonists. These data suggest that vasomotor dysfunction caused by subfailure overstretch injury may be due to activation of P2X7R. These studies have implications for our understanding of mechanical stretch injury of blood vessels and offer novel therapeutic opportunities.

  11. Activation of 5-HT7 receptors reverses NMDA-R-dependent LTD by activating PKA in medial vestibular neurons.

    Science.gov (United States)

    Li, Yan-Hai; Han, Lei; Wu, Kenneth Lap Kei; Chan, Ying-Shing

    2017-09-01

    The medial vestibular nucleus (MVN) is a major output station for neurons that project to the vestibulo-spinal pathway. MVN neurons show capacity for long-term depression (LTD) during the juvenile period. We investigated LTD of MVN neurons using whole-cell patch-clamp recordings. High frequency stimulation (HFS) robustly induced LTD in 90% of type B neurons in the MVN, while only 10% of type A neurons were responsive, indicating that type B neurons are the major contributors to LTD in the MVN. The neuromodulator serotonin (5-HT) is known to modulate LTD in neural circuits of the cerebral cortex and the hippocampus. We therefore aim to determine the action of 5-HT on the LTD of type B MVN neurons and elucidate the relevant 5-HT receptor subtypes responsible for its action. Using specific agonists and antagonists of 5-HT receptors, we found that selective activation of 5-HT 7 receptor in type B neurons in the MVN of juvenile (P13-16) rats completely abolished NMDA-receptor-mediated LTD in a protein kinase A (PKA)-dependent manner. Our finding that 5-HT restricts plasticity of type B MVN neurons via 5-HT 7 receptors offers a mechanism whereby vestibular tuning contributes to the maturation of the vestibulo-spinal circuit and highlights the role of 5-HT in postural control. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Telomerase activity-independent function of telomerase reverse transcriptase is involved in acrylamide-induced neuron damage.

    Science.gov (United States)

    Zhang, P; Pan, H; Wang, J; Liu, X; Hu, X

    2014-07-01

    Polyacrylamide is used widely in industry, and its decomposition product, acrylamide (ACR), readily finds its way into commonly consumed cosmetics and baked and fried foods. ACR exerts potent neurotoxic effects in human and animal models. Telomerase reverse transcriptase (TERT), the catalytic subunit of telomerase, traditionally has been considered to play an important role in maintaining telomere length. Emerging evidence has shown, however, that TERT plays an important role in neuroprotection by inhibiting apoptosis and excitotoxicity, and by promoting angiogenesis, neuronal survival and neurogenesis, which are closely related to the telomere-independent functions of TERT. We investigated whether and how the TERT pathway is involved in ACR induced neurotoxicity in rat cortical neurons. We found that ACR 1) significantly reduced the viability of cortical neurons as measured by MTT assay, 2) induced neuron apoptosis as revealed by FITC-conjugated Annexin V/PI double staining and flow cytometry (FACS) analysis, 3) elevated expression of cleaved caspase-3, and 4) decreased bcl-2 expression of cortical neurons. ACR also increased intracellular ROS levels in cortical neurons, increased MDA levels and reduced GSH, SOD and GSH-Px levels in mitochondria in a dose-dependent manner. We found that TERT expression in mitochondria was increased by ACR at concentrations of 2.5 and 5.0 mM, but TERT expression was decreased by 10 mM ACR. Telomerase activity, however, was undetectable in rat cortical neurons. Our results suggest that the TERT pathway is involved in ACR induced apoptosis of cortical neurons. TERT also may exert its neuroprotective role in a telomerase activity-independent way, especially in mitochondria.

  13. Mutagenic and antimutagenic activities of Artemisia absinthium volatile oil by the bacterial reverse mutation assay in Salmonella typhimurium strains TA98 and TA100

    Directory of Open Access Journals (Sweden)

    Mahboubeh Taherkhani

    2014-09-01

    Full Text Available Objective: To investigate the mutagenic and antimutagenic activities of Artemisia absinthium L. (A. absinthium essential oil by the bacterial reverse mutation assay in Salmonella typhimurium (S. typhimurium strains. Methods: Water-distilled essential oil of A. absinthium collected from Ardabil, NorthWestern Iran, was investigated for mutagenic and antimutagenic activities. In present study, the mutagenic and antimutagenic activities of A. absinthium oil were investigated by the bacterial revere mutation assay in S. typhimurium TA98 and TA100 strains with and without S9 (microsomal mutagenesis assay. Results: The comparative mutagenicity effect was seen in 1.5 mg/plate by the bacterial reverse mutation assay in S. typhimurium TA98 strains, without S9 and the excellent antimutagenicity effect was seen in 1.5 mg/plate against S. typhimurium TA100, without S9. Conclusions: The mutagenicity and antimutagenicity effects of the volatile oil of A. absinthium were seen without the presence of metabolic activation.

  14. A quantitative reverse-transcriptase PCR assay for the assessment of drug activities against intracellular Theileria annulata schizonts

    Directory of Open Access Journals (Sweden)

    Isabel Hostettler

    2014-12-01

    Full Text Available Intracellular schizonts of the apicomplexans Theileria annulata and Theileria parva immortalize bovine leucocytes thereby causing fatal immunoproliferative diseases. Buparvaquone, a hydroxynaphthoquinone related to parvaquone, is the only drug available against Theileria. The drug is only effective at the onset of infection and emerging resistance underlines the need for identifying alternative compounds. Current drug assays employ monitoring of proliferation of infected cells, with apoptosis of the infected host cell as a read-out, but it is often unclear whether active compounds directly impair the viability of the parasite or primarily induce host cell death. We here report on the development of a quantitative reverse transcriptase real time PCR method based on two Theileria genes, tasp and tap104, which are both expressed in schizonts. Upon in vitro treatment of T. annulata infected bovine monocytes with buparvaquone, TaSP and Tap104 mRNA expression levels significantly decreased in relation to host cell actin already within 4 h of drug exposure, while significant differences in host cell proliferation were detectable only after 48–72 h. TEM revealed marked alterations of the schizont ultrastructure already after 2 h of buparvaquone treatment, while the host cell remained unaffected. Expression of TaSP and Tap104 proteins showed a marked decrease only after 24 h. Therefore, the analysis of expression levels of mRNA coding for TaSP and Tap104 allows to directly measuring impairment of parasite viability. We subsequently applied this method using a series of compounds affecting different targets in other apicomplexan parasites, and show that monitoring of TaSP- and Tap104 mRNA levels constitutes a suitable tool for anti-theilerial drug development.

  15. Small-molecule screening using a human primary cell model of HIV latency identifies compounds that reverse latency without cellular activation

    Science.gov (United States)

    Yang, Hung-Chih; Xing, Sifei; Shan, Liang; O’Connell, Karen; Dinoso, Jason; Shen, Anding; Zhou, Yan; Shrum, Cynthia K.; Han, Yefei; Liu, Jun O.; Zhang, Hao; Margolick, Joseph B.; Siliciano, Robert F.

    2009-01-01

    The development of highly active antiretroviral therapy (HAART) to treat individuals infected with HIV-1 has dramatically improved patient outcomes, but HAART still fails to cure the infection. The latent viral reservoir in resting CD4+ T cells is a major barrier to virus eradication. Elimination of this reservoir requires reactivation of the latent virus. However, strategies for reactivating HIV-1 through nonspecific T cell activation have clinically unacceptable toxicities. We describe here the development of what we believe to be a novel in vitro model of HIV-1 latency that we used to search for compounds that can reverse latency. Human primary CD4+ T cells were transduced with the prosurvival molecule Bcl-2, and the resulting cells were shown to recapitulate the quiescent state of resting CD4+ T cells in vivo. Using this model system, we screened small-molecule libraries and identified a compound that reactivated latent HIV-1 without inducing global T cell activation, 5-hydroxynaphthalene-1,4-dione (5HN). Unlike previously described latency-reversing agents, 5HN activated latent HIV-1 through ROS and NF-κB without affecting nuclear factor of activated T cells (NFAT) and PKC, demonstrating that TCR pathways can be dissected and utilized to purge latent virus. Our study expands the number of classes of latency-reversing therapeutics and demonstrates the utility of this in vitro model for finding strategies to eradicate HIV-1 infection. PMID:19805909

  16. Comparison of {gamma}-ray profile across active normal and reverse faults; Seidansogata to gyakudansogata katsudanso ni okeru hoshano tansa kekka no hikaku

    Energy Technology Data Exchange (ETDEWEB)

    Iwata, A; Wada, N; Sumi, H [Shimada Technical Consultants, Ltd., Shimane (Japan); Yamauchi, S; Iga, T [Shimane Univ., Shimane (Japan)

    1996-10-01

    Active faults confirmed at trench and outcrop were surveyed by the {gamma}-ray spectrometry. The active fault found at trench is a normal fault, and that found at outcrop is a reverse fault. The {gamma}-ray spectral characteristics of these two types of faults were compared to each other. The normal fault is named as Asagane fault located in Aimi-machi, Saihaku-gun, Tottori prefecture. The reverse fault is named as Yokota reverse fault located in Yokota-cho, Nita-gun, Shimane prefecture. Rises of radon gas indicating the existence of opening cracks were confirmed above the fault for the normal fault, and at the side of thrust block for the reverse fault. It was considered that such characteristics were caused by the difference of fault formation in the tensile stress field and in the compressive stress field. It was also reconfirmed that much more information as to faults can be obtained by the combined exploration method using the total counting method and the spectral method. 14 refs., 7 figs.

  17. The reverse-mode NCX1 activity inhibitor KB-R7943 promotes prostate cancer cell death by activating the JNK pathway and blocking autophagic flux.

    Science.gov (United States)

    Long, Zhou; Chen, BaiJun; Liu, Qian; Zhao, Jiang; Yang, ZhenXing; Dong, XingYou; Xia, LiuBin; Huang, ShengQuan; Hu, XiaoYan; Song, Bo; Li, LongKun

    2016-07-05

    We explored the effects of KB-R7943, an inhibitor of reverse-mode NCX1 activity, in prostate cancer (PCa). NCX1 was overexpressed in PCa tissues and cell lines, and higher NCX1 levels were associated higher PCa grades. At concentrations greater than 10 μM, KB-R7943 dose-dependently decreased PC3 and LNCaP cell viability. KB-R7943 also increased cell cycle G1/S phase arrest and induced apoptosis in PC3 cells. KB-R7943 increased autophagosome accumulation in PCa cells as indicated by increases in LC3-II levels and eGFP-LC3 puncta. Combined treatment with chloroquine (CQ) and KB-R7943 decreased P62 and increased LC3-II protein levels in PC3 cells, indicating that KB-R7943 blocked autophagic flux. KB-R7943 induced autophagosome accumulation mainly by downregulating the PI3K/AKT/m-TOR pathway and upregulating the JNK pathway. In xenograft experiments, KB-R7943 inhibited tumor growth. Combined treatment with KB-R7943 and an autophagy inhibitor inhibited growth and increased apoptosis. These results indicate that KB-R7943 promotes cell death in PCa by activating the JNK signaling pathway and blocking autophagic flux.

  18. Selective activation of M4 muscarinic acetylcholine receptors reverses MK-801-induced behavioral impairments and enhances associative learning in rodents

    DEFF Research Database (Denmark)

    Bubser, Michael; Bridges, Thomas M; Dencker, Ditte

    2014-01-01

    PAMs, enabling a more extensive characterization of M4 actions in rodent models. We used VU0467154 to test the hypothesis that selective potentiation of M4 receptor signaling could ameliorate the behavioral, cognitive, and neurochemical impairments induced by the noncompetitive NMDAR antagonist MK-801....... VU0467154 produced a robust dose-dependent reversal of MK-801-induced hyperlocomotion and deficits in preclinical models of associative learning and memory functions, including the touchscreen pairwise visual discrimination task in wild-type mice, but failed to reverse these stimulant...

  19. Alterations in brain Protein Kinase A activity and reversal of morphine tolerance by two fragments of native Protein Kinase A inhibitor peptide (PKI).

    Science.gov (United States)

    Dalton, George D; Smith, Forrest L; Smith, Paul A; Dewey, William L

    2005-04-01

    Two peptide fragments of native Protein Kinase A inhibitor (PKI), PKI-(6-22)-amide and PKI-(Myr-14-22)-amide, significantly reversed low-level morphine antinociceptive tolerance in mice. The inhibition of Protein Kinase A (PKA) activity by both peptide fragments was then measured in specific brain regions (thalamus, periaqueductal gray (PAG), and medulla) and in lumbar spinal cord (LSC), which in previous studies have been shown to play a role in morphine-induced analgesia. In drug naive animals, cytosolic PKA activity was greater than particulate PKA activity in each region, while cytosolic and particulate PKA activities were greater in thalamus and PAG compared to medulla and LSC. The addition of both peptides to homogenates from each region completely abolished cytosolic and particulate PKA activities in vitro. Following injection into the lateral ventricle of the brain of drug naive mice and morphine-tolerant mice, both peptides inhibited PKA activity in the cytosolic, but not the particulate fraction of LSC. In addition, cytosolic and particulate PKA activities were inhibited by both peptides in thalamus. These results demonstrate that the inhibition of PKA reverses morphine tolerance. Moreover, the inhibition of PKA activity in specific brain regions and LSC from morphine-tolerant mice by PKI analogs administered i.c.v. is evidence that PKA plays a role in morphine tolerance.

  20. Real-time zymography and reverse zymography: a method for detecting activities of matrix metalloproteinases and their inhibitors using FITC-labeled collagen and casein as substrates.

    Science.gov (United States)

    Hattori, Shunji; Fujisaki, Hitomi; Kiriyama, Tomomi; Yokoyama, Tsukao; Irie, Shinkichi

    2002-02-01

    Zymography and reverse zymography are widely used techniques for identifying the proteolytic activity of enzymes and the presence of protease inhibitors in polyacrylamide gels. In the current studies, we utilized a fluorescein-isothiocyanate-labeled substrate to develop novel zymographic and reverse zymographic methods for detecting matrix metalloproteinases and tissue inhibitors of the metalloproteinases, respectively. Using a transilluminator, the results can be observed visually without stopping the enzymatic reaction. For this reason, we have named these methods real-time zymography and real-time reverse zymography. These methods have the following advantages compared with conventional protocols: (1) because the reaction can be repeatedly monitored on the polyacrylamide gels, optimization of the incubation time can be achieved without preliminary analyses; (2) higher sensitivity is achieved with a lower amount of substrate than with conventional methods; (3) a semi-quantitative analysis of matrix metalloproteinases is possible. An additional advantage of the real-time reverse zymography is that, because the fluorescence detection is specific for substrate digestion, the inhibitor bands can be easily distinguished from contaminating proteins.

  1. Bidirectional Control of Reversal in a Dual Action Task by Direct and Indirect Pathway Activation in the Dorsolateral Striatum in Mice

    Directory of Open Access Journals (Sweden)

    Muriel Laurent

    2017-12-01

    Full Text Available The striatum is a key brain structure involved in the processing of cognitive flexibility, which results from the balance between the flexibility demanded for novel learning of motor actions and the inflexibility required to preserve previously learned actions. In particular, the dorsolateral portion of the striatum (DLS is engaged in the learning of action sequence. This process is temporally driven by fine adjustments in the function of the two main neuronal populations of the striatum, known as the direct pathway medium spiny neurons (dMSNs and indirect pathway medium spiny neurons (iMSNs. Here, using optogenetics, behavioral, and electrophysiological tools, we addressed the relative role of both neuronal populations in the acquisition of a reversal dual action sequence in the DLS. While the channelrhodopsin-induced activation of dMSNs and iMSNs of the DLS did not induce changes in the learning rate of the sequence, the specific activation of the dMSNs of the DLS facilitated the acquisition of a reversal dual action sequence; the activation of iMSNs induced a significant deficit in the acquisition of the same task. Taken together our results indicate an antagonistic relationship between dMSNs and iMSNs on the acquisition of a reversal dual action sequence.

  2. Altered brain activation in a reversal learning task unmasks adaptive changes in cognitive control in writer's cramp.

    Science.gov (United States)

    Zeuner, Kirsten E; Knutzen, Arne; Granert, Oliver; Sablowsky, Simone; Götz, Julia; Wolff, Stephan; Jansen, Olav; Dressler, Dirk; Schneider, Susanne A; Klein, Christine; Deuschl, Günther; van Eimeren, Thilo; Witt, Karsten

    2016-01-01

    Previous receptor binding studies suggest dopamine function is altered in the basal ganglia circuitry in task-specific dystonia, a condition characterized by contraction of agonist and antagonist muscles while performing specific tasks. Dopamine plays a role in reward-based learning. Using fMRI, this study compared 31 right-handed writer's cramp patients to 35 controls in reward-based learning of a probabilistic reversal-learning task. All subjects chose between two stimuli and indicated their response with their left or right index finger. One stimulus response was rewarded 80%, the other 20%. After contingencies reversal, the second stimulus response was rewarded in 80%. We further linked the DRD2/ANKK1-TaqIa polymorphism, which is associated with 30% reduction of the striatal dopamine receptor density with reward-based learning and assumed impaired reversal learning in A + subjects. Feedback learning in patients was normal. Blood-oxygen level dependent (BOLD) signal in controls increased with negative feedback in the insula, rostral cingulate cortex, middle frontal gyrus and parietal cortex (pFWE based learning. The dACC is connected with the basal ganglia-thalamo-loop modulated by dopaminergic signaling. This finding suggests disturbed integration of reinforcement history in decision making and implicate that the reward system might contribute to the pathogenesis in writer's cramp.

  3. Lentin, a novel and potent antifungal protein from shitake mushroom with inhibitory effects on activity of human immunodeficiency virus-1 reverse transcriptase and proliferation of leukemia cells.

    Science.gov (United States)

    Ngai, Patrick H K; Ng, T B

    2003-11-14

    From the fruiting bodies of the edible mushroom Lentinus edodes, a novel protein designated lentin with potent antifungal activity was isolated. Lentin was unadsorbed on DEAE-cellulose, and adsorbed on Affi-gel blue gel and Mono S. The N-terminal sequence of lentin manifested similarity to endoglucanase. Lentin, which had a molecular mass of 27.5 kDa, inhibited mycelial growth in a variety of fungal species including Physalospora piricola, Botrytis cinerea and Mycosphaerella arachidicola. Lentin also exerted an inhibitory activity on HIV-1 reverse transcriptase and proliferation of leukemia cells.

  4. Trans-activation of the 5' to 3' viral DNA strand transfer by nucleocapsid protein during reverse transcription of HIV1 RNA.

    Science.gov (United States)

    Darlix, J L; Vincent, A; Gabus, C; de Rocquigny, H; Roques, B

    1993-08-01

    Two DNA strand transfer reactions take place during reverse transcription of the retroviral genome. The first transfer, that of the minus-strand strong stop DNA from the 5' end of the viral RNA to the 3' end, has been studied in vitro with two RNAs mimicking the 5' and 3' regions of the HIV1 genome and with nucleocapsid protein, NCp7, and reverse transcriptase. The results show that NCp7 strongly activates the 5' to 3' DNA strand transfer during reverse transcription while a basic peptide resembling NCp7 is inactive. Activation of the first transfer by several NCp7 derived peptides and the influence of the terminal redundancies (R) present at the 5' and 3' ends of HIV1 RNA were also examined. The first transfer is optimal in the presence of intact NCp7 and necessitates R on both the 5' and 3' RNAs. Sequencing of full length viral DNA products reveals approximately 40% misincorporations at the first nucleotide beyond the transfer point. If such base misincorporations occur during proviral DNA synthesis with possible homologous recombinations it may well contribute to the high level of genetic variability of HIV.

  5. Class 1-Selective Histone Deacetylase (HDAC) Inhibitors Enhance HIV Latency Reversal while Preserving the Activity of HDAC Isoforms Necessary for Maximal HIV Gene Expression.

    Science.gov (United States)

    Zaikos, Thomas D; Painter, Mark M; Sebastian Kettinger, Nadia T; Terry, Valeri H; Collins, Kathleen L

    2018-03-15

    Combinations of drugs that affect distinct mechanisms of HIV latency aim to induce robust latency reversal leading to cytopathicity and elimination of the persistent HIV reservoir. Thus far, attempts have focused on combinations of protein kinase C (PKC) agonists and pan-histone deacetylase inhibitors (HDIs) despite the knowledge that HIV gene expression is regulated by class 1 histone deacetylases. We hypothesized that class 1-selective HDIs would promote more robust HIV latency reversal in combination with a PKC agonist than pan-HDIs because they preserve the activity of proviral factors regulated by non-class 1 histone deacetylases. Here, we show that class 1-selective agents used alone or with the PKC agonist bryostatin-1 induced more HIV protein expression per infected cell. In addition, the combination of entinostat and bryostatin-1 induced viral outgrowth, whereas bryostatin-1 combinations with pan-HDIs did not. When class 1-selective HDIs were used in combination with pan-HDIs, the amount of viral protein expression and virus outgrowth resembled that of pan-HDIs alone, suggesting that pan-HDIs inhibit robust gene expression induced by class 1-selective HDIs. Consistent with this, pan-HDI-containing combinations reduced the activity of NF-κB and Hsp90, two cellular factors necessary for potent HIV protein expression, but did not significantly reduce overall cell viability. An assessment of viral clearance from in vitro cultures indicated that maximal protein expression induced by class 1-selective HDI treatment was crucial for reservoir clearance. These findings elucidate the limitations of current approaches and provide a path toward more effective strategies to eliminate the HIV reservoir. IMPORTANCE Despite effective antiretroviral therapy, HIV evades eradication in a latent form that is not affected by currently available drug regimens. Pharmacologic latency reversal that leads to death of cellular reservoirs has been proposed as a strategy for

  6. PENINGKATKAN HASIL BELAJAR PKN KELAS V MELALUI MODEL ACTIVE LEARNING (TIPE ROLE REVERSAL QUESTION SDN 4 DOPLANG KECAMATAN JATI KABUPATEN BLORA

    Directory of Open Access Journals (Sweden)

    Ambar Susilo Murti

    2016-12-01

    Full Text Available Constitution No. 20 of 2003, concerning Citizenship Education (PKN is a compulsory subject for primary education, secondary, and compulsory subjects for higher education. The purpose of this study is to improve learning outcomes Civics using Active Learning Model Type Question Role Reversal in Class V SDN 4 Doplang Jati district of  Blora. This research was a class action (classroom action research. The stages as follows: (1 planning, (2 implementation, (3 observation and (4 reflection. The result of research indicating that students who received grades ≥70 the first cycle increased by 25%  from the initial 44% to 69%. Then students who scored ≥70 on the second cycle increased 28% to 97%. The average value of the first cycle increased by 8.75% from 66.53 into 75.28 early in the first cycle and then the second cycle of the average value increased again by 10.97% to 86.25. Researchers suggest teachers should encourage students to be more daring in expressing opinions, questions and ideas that are not held only in Civics alone but on other subjects. In addition, teachers are expected to use active learning model of the type of role reversal question in improving student learning outcomes in other subjects. As for the school is expected to provide training to teachers on implementing learning activities are innovative and creative. Keywords: active learning, civic education, learning outcomes.

  7. p53-dependent manner of persistent activation of the radiation-induced reversion in the pink-eyed unstable mouse embryo

    International Nuclear Information System (INIS)

    Shiraishi, K.; Yonezawa, M.; Niwa, O.

    2003-01-01

    Full text: We previously reported that radiation has an ability to induce genomic instability which causes delayed and untargeted mutation. These mutations aren't accounted for by the usual relationship between DNA damages and repair. However, the mechanisms of a long-term memory of DNA damage and the persistence of up-regulated recombination activity have yet to be elucidated. The mouse pink-eyed unstable (pun) mutation is due to an intragenic duplication of the pink-eyed dilution locus and frequently reverts black to the wild type in germ cells as well as somatic cells. The frequency of reversion was estimated by counting cluster of pigment cells in retinal pigment epithelium. Twice increase of the reversion was observed in F1 mice born to 6Gy irradiated male at spermatozoa stage, but not at other spermatogenesis stages( -tid, -cyte, -gonia ). Trans-genarational effect in F2 mice also didn't observe. Therefore, this phenomenon only occurs under the restricted germ cell stage. Additionally, the reversion frequency of p53 deficient F1 mouse born to irradiated sperm was less than irradiated wild mouse. 5aza-dc chemical agent, which is DNA methylation emzyme inhibitor, also suppressed pun allele recombination in mouse embryo. These data indicate that p53 contributes delayed and untargeted mutation, perhaps, by regulation of DNA metylation status

  8. Reversible Statistics

    DEFF Research Database (Denmark)

    Tryggestad, Kjell

    2004-01-01

    The study aims is to describe how the inclusion and exclusion of materials and calculative devices construct the boundaries and distinctions between statistical facts and artifacts in economics. My methodological approach is inspired by John Graunt's (1667) Political arithmetic and more recent work...... within constructivism and the field of Science and Technology Studies (STS). The result of this approach is here termed reversible statistics, reconstructing the findings of a statistical study within economics in three different ways. It is argued that all three accounts are quite normal, albeit...... in different ways. The presence and absence of diverse materials, both natural and political, is what distinguishes them from each other. Arguments are presented for a more symmetric relation between the scientific statistical text and the reader. I will argue that a more symmetric relation can be achieved...

  9. Effect of captan on the exonuclease activities of DNA polymerase I from E. coli and reverse transcriptase from avian myeloblastosis virus

    International Nuclear Information System (INIS)

    Freeman-Wittig, M.J.B.

    1986-01-01

    The DNA pol I polymerase activity is known to be inhibited by captan. When captan was tested for its ability to alter the exonuclease activity of DNA pol I, degradation was enhanced at high substrate concentrations. At low concentrations of DNA, captan was inhibitory. By assaying the two exonuclease activities separately it was shown that the differential effect by captan was the result of a combined inhibition of the 3' → 5' exonuclease and enhancement of the 5' → 3' exonuclease. Studies employing [ 14 C] captan showed that the alterations in DNA pol I activities were a result of the irreversible binding of captan to the enzyme in a ratio of 1:1. The effect of captan on AMV reverse transcriptase RNase H activity was also studied. RNase H activity appeared to be more sensitive to captan than was the polymerase activity. Inhibition of the polymerase activity could be prevented by deoxynucleotide triphosphate and was increased by templateprimer. RNase H activity, which showed a sigmoidal relationship between activity and substrate concentration, decreased in V/sub max/ with no change in the Hill coefficient in the presence of captan

  10. More efficient reversal of dabigatran inhibition of coagulation by activated prothrombin complex concentrate or recombinant factor VIIa than by four-factor prothrombin complex concentrate.

    Science.gov (United States)

    Lindahl, Tomas L; Wallstedt, Maria; Gustafsson, Kerstin M; Persson, Egon; Hillarp, Andreas

    2015-03-01

    The number of patients on antithrombotic treatment due to atrial fibrillation and venous thromboembolism is increasing fast due to an aging population. A growing proportion will be treated with novel oral anticoagulants, the first in clinical use was the direct oral thrombin inhibitor dabigatran (Pradaxa®). A small percentage of the patients on dabigatran will experience serious bleeding or be in need of urgent surgery. The aim of this study was to test the effects of different hemostatic agents in potentially reversing the anticoagulant effects in vitro in blood or platelet-rich plasma (PRP) spiked with dabigatran. Whole blood or PRP was spiked with the active substance dabigatran, 200 μg/L. We measured clotting time being induced by 1.4 pmol/L tissue factor using the instrument ReoRox2™ and initial clot growth velocity from a tissue factor covered surface using the instrument Thrombodynamics Analyzer T-2™. Dabigatran prolonged clotting time 5-fold but reduced clot growth velocity only slightly. The reversing effects of prothrombin complex concentrates (PCC), activated PCC (APCC) and recombinant activated factor VII (rFVIIa) were then tested. APCC (1.8 U/mL) reduced the prolonged clotting time by 1/3, rFVIIa (2 μg/L) only slightly (n = 10-20). The reduction was not significant using Mann-Whitney test but significant using t-test with Bonferronis' correction for multiple comparisons, whereas PCC (0.56 U/mL) had no effect on clotting time. APCC doubled initial clot growth velocity, although even more in the absence of dabigatran. In conclusion, APCC and rFVIIa, but not PCC, seem to reverse, at least partially, some effects of dabigatran on coagulation parameters. Systematic evaluation of case reports, registries and, ultimately, randomized clinical trials are needed to elucidate potential benefit for patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Synthesis of Fischer carbene complexes of iridium by C-H bond activation of methyl and cyclic ethers: Evidence for reversible {alpha}-hydrogen migration

    Energy Technology Data Exchange (ETDEWEB)

    Luecke, H.F.; Arndtsen, B.A.; Burger, P.; Bergman, R.G. [Lawrence Berkeley Lab., CA (United States)]|[Univ. of California, Berkeley, CA (United States)

    1996-03-13

    We report here a mild and versatile route to Fischer carbene complexes of iridium via the activation of C-H bonds of methyl and cyclic ethers, along with our preliminary studies of this rare family of carbene complexes. Theoretical studies suggest that {alpha}-hydrogen migrations can be kinetically favorable if a coordinatively unsaturated species can be accessed. Thus, the lability of the triflate ligand presumably facilitates this process. Further evidence for the rapidity, as well as reversibility, of this rearrangement was obtained by NMR analysis. 20 refs.

  12. A case of posterior reversible encephalopathy syndrome in the setting of post-partum preeclampsia with suppressed plasma aldosterone levels and plasma renin activity

    Directory of Open Access Journals (Sweden)

    Aurelio Negro

    2013-12-01

    Full Text Available Posterior reversible encephalopathy syndrome (PRES is characterized by headache, altered mental status, visual loss, and seizures. PRES is associated with neuroradiological findings: white matter abnormalities, predominantly in the parieto-occipital regions of the brain. PRES has been described in association with hypertensive encephalopathy, eclampsia, renal failure, or following immunosuppressive or anticancer therapy. We report a case of PRES in a severe preeclampsia occurring in the late postpartum period, with suppressed plasma aldosterone levels and plasma renin activity. These laboratory abnormalities may be due to an apparent mineralocorticoid excess syndrome.

  13. Taurine reverses sodium fluoride-mediated increase in inflammation, caspase-3 activity, and oxidative damage along the brain-pituitary-gonadal axis in male rats.

    Science.gov (United States)

    Adedara, Isaac A; Olabiyi, Bolanle F; Ojuade, TeminiJesu D; Idris, Umar F; Onibiyo, Esther M; Farombi, Ebenezer O

    2017-09-01

    Excessive exposure to fluoride is associated with male reproductive dysfunction in humans and animals. Taurine (2-aminoethane sulfonic acid) is a free intracellular β-amino acid with antioxidant, anti-inflammatory, and neuroprotective properties. However, the effect of taurine on fluoride-induced reproductive toxicity has not been reported. The present study investigated the influence of taurine on sodium fluoride (NaF)-induced functional changes along the brain-pituitary-gonadal axis in male rats. NaF was administered singly in drinking water at 15 mg·L -1 alone or orally co-administered by gavage with taurine at 100 and 200 mg·(kg body mass) -1 for 45 consecutive days. Results showed that taurine significantly prevented NaF-induced increase in oxidative stress indices as well as augmented antioxidant enzymes activities and glutathione level in the brain, testes, and epididymis of the treated rats. Moreover, taurine reversed NaF-induced elevation in inflammatory biomarkers and caspase-3 activity as well as histological damage in the brain, testes, and epididymis of the treated rats. The significant reversal of NaF-induced decreases in testosterone level and testicular activities of acid phosphatase, alkaline phosphatase, and lactate dehydrogenase by taurine was accompanied by enhancement of sperm functional characteristics in the treated rats. Taurine may be a possible chemopreventive candidate against reproductive dysfunction resulting from fluoride exposure.

  14. Intelligent shell feedback control in EXTRAP T2R reversed field pinch with partial coverage of the toroidal surface by a discrete active coil array

    Science.gov (United States)

    Yadikin, D.; Brunsell, P. R.; Drake, J. R.

    2006-01-01

    An active feedback system is required for long pulse operation of the reversed field pinch (RFP) device to suppress resistive wall modes (RWMs). A general feature of a feedback system using a discrete active coil array is a coupling effect which arises when a set of side band modes determined by the number of active coils is produced. Recent results obtained on the EXTRAP T2R RFP demonstrated the suppression of independent m = 1 RWMs using an active feedback system with a two-dimensional array of discrete active coils in the poloidal and toroidal directions. One of the feedback algorithms used is the intelligent shell feedback scheme. Active feedback systems having different number of active coils in the poloidal (Mc) and toroidal (Nc) directions (Mc × Nc = 2 × 32 and Mc × Nc = 4 × 16) are studied. Different side band effects are seen for these configurations. A significant prolongation of the plasma discharge is achieved for the intelligent shell feedback scheme using the 2 × 32 active coil configuration. This is attributed to the side band sets including only one of the dominant unstable RWMs and avoiding coupling to resonant modes. Analog proportional-integral-derivative controllers are used in the feedback system. Regimes with different values of the proportional gain are studied. The requirement of the proportional-integral control for low proportional gain and proportional-derivative control for high proportional gain is seen in the experiments.

  15. Reversible Inactivation of the Higher Order Auditory Cortex during Fear Memory Consolidation Prevents Memory-Related Activity in the Basolateral Amygdala during Remote Memory Retrieval.

    Science.gov (United States)

    Cambiaghi, Marco; Renna, Annamaria; Milano, Luisella; Sacchetti, Benedetto

    2017-01-01

    Recent findings have shown that the auditory cortex, and specifically the higher order Te2 area, is necessary for the consolidation of long-term fearful memories and that it interacts with the amygdala during the retrieval of long-term fearful memories. Here, we tested whether the reversible blockade of Te2 during memory consolidation may affect the activity changes occurring in the amygdala during the retrieval of fearful memories. To address this issue, we blocked Te2 in a reversible manner during memory consolidation processes. After 4 weeks, we assessed the activity of Te2 and individual nuclei of the amygdala during the retrieval of long-term memories. Rats in which Te2 was inactivated upon memory encoding showed a decreased freezing and failed to show Te2-to-basolateral amygdala (BLA) synchrony during memory retrieval. In addition, the expression of the immediate early gene zif268 in the lateral, basal and central amygdala nuclei did not show memory-related enhancement. As all sites were intact upon memory retrieval, we propose that the auditory cortex represents a key node in the consolidation of fear memories and it is essential for amygdala nuclei to support memory retrieval process.

  16. Active PI3K pathway causes an invasive phenotype which can be reversed or promoted by blocking the pathway at divergent nodes.

    Directory of Open Access Journals (Sweden)

    Jeffrey J Wallin

    Full Text Available The PTEN/PI3K pathway is commonly mutated in cancer and therefore represents an attractive target for therapeutic intervention. To investigate the primary phenotypes mediated by increased pathway signaling in a clean, patient-relevant context, an activating PIK3CA mutation (H1047R was knocked-in to an endogenous allele of the MCF10A non-tumorigenic human breast epithelial cell line. Introduction of an endogenously mutated PIK3CA allele resulted in a marked epithelial-mesenchymal transition (EMT and invasive phenotype, compared to isogenic wild-type cells. The invasive phenotype was linked to enhanced PIP(3 production via a S6K-IRS positive feedback mechanism. Moreover, potent and selective inhibitors of PI3K were highly effective in reversing this phenotype, which is optimally revealed in 3-dimensional cell culture. In contrast, inhibition of Akt or mTOR exacerbated the invasive phenotype. Our results suggest that invasion is a core phenotype mediated by increased PTEN/PI3K pathway activity and that therapeutic agents targeting different nodes of the PI3K pathway may have dramatic differences in their ability to reverse or promote cancer metastasis.

  17. Active methamphetamine use is associated with transmitted drug resistance to non-nucleoside reverse transcriptase inhibitors in individuals with HIV infection of unknown duration.

    Science.gov (United States)

    Cachay, Edward R; Moini, Niousha; Kosakovsky Pond, Sergei L; Pesano, Rick; Lie, Yolanda S; Aiem, Heidi; Butler, David M; Letendre, Scott; Mathews, Wm Christopher; Smith, Davey M

    2007-01-01

    Frequent methamphetamine use among recently HIV infected individuals is associated with transmitted drug resistance (TDR) to non-nucleoside reverse transcriptase inhibitors (NNRTI); however, the reversion time of TDR to drug susceptible HIV may exceed 3 years. We assessed whether recreational substance use is associated with detectable TDR among individuals newly diagnosed with HIV infection of unknown duration. Cross-sectional analysis. Subjects were enrolled at the University California, San Diego Early Intervention Program. Demographic, clinical and substance use data were collected using structured interviews. Genotypic resistance testing was performed using GeneSeq, Monogram Biosciences. We analyzed the association between substance use and TDR using bivariate analyses and the corresponding transmission networks using phylogenetic models. Between April 2004 and July 2006, 115 individuals with genotype data were enrolled. The prevalence of alcohol, marijuana and methamphetamine use were 98%, 71% and 64% respectively. Only active methamphetamine use in the 30 days prior to HIV diagnosis was independently associated with TDR to NNRTI (OR: 6.6; p=0.002). Despite not knowing the duration of their HIV infection, individuals reporting active methamphetamine use in the 30 days prior to HIV diagnosis are at an increased risk of having HIV strains that are resistant to NNRTI.

  18. Active Methamphetamine Use is Associated with Transmitted Drug Resis-tance to Non-Nucleoside Reverse Transcriptase Inhibitors in Individuals with HIV Infection of Unknown Duration

    Science.gov (United States)

    Cachay, Edward R; Moini, Niousha; Kosakovsky Pond, Sergei L; Pesano, Rick; Lie, Yolanda S; Aiem, Heidi; Butler, David M; Letendre, Scott; Mathews, Wm. Christopher; Smith, Davey M

    2007-01-01

    Background: Frequent methamphetamine use among recently HIV infected individuals is associated with transmitted drug resistance (TDR) to non-nucleoside reverse transcriptase inhibitors (NNRTI); however, the reversion time of TDR to drug susceptible HIV may exceed 3 years. We assessed whether recreational substance use is associated with detectable TDR among individuals newly diagnosed with HIV infection of unknown duration. Design: Cross-sectional analysis. Methods: Subjects were enrolled at the University California, San Diego Early Intervention Program. Demographic, clinical and substance use data were collected using structured interviews. Genotypic resistance testing was performed using GeneSeq™, Monogram Biosciences. We analyzed the association between substance use and TDR using bivariate analyses and the corresponding transmission networks using phylogenetic models. Results: Between April 2004 and July 2006, 115 individuals with genotype data were enrolled. The prevalence of alcohol, marijuana and methamphetamine use were 98%, 71% and 64% respectively. Only active methamphetamine use in the 30 days prior to HIV diagnosis was independently associated with TDR to NNRTI (OR: 6.6; p=0.002). Conclusion: Despite not knowing the duration of their HIV infection, individuals reporting active methamphetamine use in the 30 days prior to HIV diagnosis are at an increased risk of having HIV strains that are resistant to NNRTI. PMID:18923691

  19. Reversible Capture and Release of Cl2 and Br2 with a Redox-Active Metal-Organic Framework.

    Science.gov (United States)

    Tulchinsky, Yuri; Hendon, Christopher H; Lomachenko, Kirill A; Borfecchia, Elisa; Melot, Brent C; Hudson, Matthew R; Tarver, Jacob D; Korzyński, Maciej D; Stubbs, Amanda W; Kagan, Jacob J; Lamberti, Carlo; Brown, Craig M; Dincă, Mircea

    2017-04-26

    Extreme toxicity, corrosiveness, and volatility pose serious challenges for the safe storage and transportation of elemental chlorine and bromine, which play critical roles in the chemical industry. Solid materials capable of forming stable nonvolatile compounds upon reaction with elemental halogens may partially mitigate these challenges by allowing safe halogen release on demand. Here we demonstrate that elemental halogens quantitatively oxidize coordinatively unsaturated Co(II) ions in a robust azolate metal-organic framework (MOF) to produce stable and safe-to-handle Co(III) materials featuring terminal Co(III)-halogen bonds. Thermal treatment of the oxidized MOF causes homolytic cleavage of the Co(III)-halogen bonds, reduction to Co(II), and concomitant release of elemental halogens. The reversible chemical storage and thermal release of elemental halogens occur with no significant losses of structural integrity, as the parent cobaltous MOF retains its crystallinity and porosity even after three oxidation/reduction cycles. These results highlight a material operating via redox mechanism that may find utility in the storage and capture of other noxious and corrosive gases.

  20. Prenatal androgenization of female mice programs an increase in firing activity of gonadotropin-releasing hormone (GnRH) neurons that is reversed by metformin treatment in adulthood.

    Science.gov (United States)

    Roland, Alison V; Moenter, Suzanne M

    2011-02-01

    Prenatal androgenization (PNA) of female mice with dihydrotestosterone programs reproductive dysfunction in adulthood, characterized by elevated luteinizing hormone levels, irregular estrous cycles, and central abnormalities. Here, we evaluated activity of GnRH neurons from PNA mice and the effects of in vivo treatment with metformin, an activator of AMP-activated protein kinase (AMPK) that is commonly used to treat the fertility disorder polycystic ovary syndrome. Estrous cycles were monitored in PNA and control mice before and after metformin administration. Before metformin, cycles were longer in PNA mice and percent time in estrus lower; metformin normalized cycles in PNA mice. Extracellular recordings were used to monitor GnRH neuron firing activity in brain slices from diestrous mice. Firing rate was higher and quiescence lower in GnRH neurons from PNA mice, demonstrating increased GnRH neuron activity. Metformin treatment of PNA mice restored firing activity and LH to control levels. To assess whether AMPK activation contributed to the metformin-induced reduction in GnRH neuron activity, the AMPK antagonist compound C was acutely applied to cells. Compound C stimulated cells from metformin-treated, but not untreated, mice, suggesting that AMPK was activated in GnRH neurons, or afferent neurons, in the former group. GnRH neurons from metformin-treated mice also showed a reduced inhibitory response to low glucose. These studies indicate that PNA causes enhanced firing activity of GnRH neurons and elevated LH that are reversible by metformin, raising the possibility that central AMPK activation by metformin may play a role in its restoration of reproductive cycles in polycystic ovary syndrome.

  1. A Novel Lectin with Antiproliferative and HIV-1 Reverse Transcriptase Inhibitory Activities from Dried Fruiting Bodies of the Monkey Head Mushroom Hericium erinaceum

    Science.gov (United States)

    Li, Yanrui; Zhang, Guoqing; Ng, Tzi Bun; Wang, Hexiang

    2010-01-01

    A lectin designated as Hericium erinaceum agglutinin (HEA) was isolated from dried fruiting bodies of the mushroom Hericium erinaceum with a chromatographic procedure which entailed DEAE-cellulose, CM-cellulose, Q-Sepharose, and FPLC Superdex 75. Its molecular mass was estimated to be 51 kDa and its N-terminal amino acid sequences was distinctly different from those of other isolated mushroom lectins. The hemagglutinating activity of HEA was inhibited at the minimum concentration of 12.5 mM by inulin. The lectin was stable at pH 1.9–12.1 and at temperatures up to 70°C, but was inhibited by Hg2+, Cu2+, and Fe3+ ions. The lectin exhibited potent mitogenic activity toward mouse splenocytes, and demonstrated antiproliferative activity toward hepatoma (HepG2) and breast cancer (MCF7) cells with an IC50 of 56.1 μM and 76.5 μM, respectively. It manifested HIV-1 reverse transcriptase inhibitory activity with an IC50 of 31.7 μM. The lectin exhibited potent mitogenic activity toward murine splenocytes but was devoid of antifungal activity. PMID:20625408

  2. A Novel Lectin with Antiproliferative and HIV-1 Reverse Transcriptase Inhibitory Activities from Dried Fruiting Bodies of the Monkey Head Mushroom Hericium erinaceum

    Directory of Open Access Journals (Sweden)

    Yanrui Li

    2010-01-01

    Full Text Available A lectin designated as Hericium erinaceum agglutinin (HEA was isolated from dried fruiting bodies of the mushroom Hericium erinaceum with a chromatographic procedure which entailed DEAE-cellulose, CM-cellulose, Q-Sepharose, and FPLC Superdex 75. Its molecular mass was estimated to be 51 kDa and its N-terminal amino acid sequences was distinctly different from those of other isolated mushroom lectins. The hemagglutinating activity of HEA was inhibited at the minimum concentration of 12.5 mM by inulin. The lectin was stable at pH 1.9–12.1 and at temperatures up to 70∘C, but was inhibited by Hg2+, Cu2+, and Fe3+ ions. The lectin exhibited potent mitogenic activity toward mouse splenocytes, and demonstrated antiproliferative activity toward hepatoma (HepG2 and breast cancer (MCF7 cells with an IC50 of 56.1 M and 76.5 M, respectively. It manifested HIV-1 reverse transcriptase inhibitory activity with an IC50 of 31.7 M. The lectin exhibited potent mitogenic activity toward murine splenocytes but was devoid of antifungal activity.

  3. Pharmacokinetics and pharmacodynamics of orally administered acetylenic tricyclic bis(cyanoenone), a highly potent Nrf2 activator with a reversible covalent mode of action

    Energy Technology Data Exchange (ETDEWEB)

    Kostov, Rumen V.; Knatko, Elena V.; McLaughlin, Lesley A.; Henderson, Colin J. [Jacqui Wood Cancer Centre, Division of Cancer Research, Medical Research Institute, University of Dundee, Dundee, DD1 9SY, Scotland (United Kingdom); Zheng, Suqing [Department of Chemistry and Institute of Chemical Biology & Drug Discovery, Stony Brook University, Stony Brook, NY, 11794 (United States); Huang, Jeffrey T.-J. [Jacqui Wood Cancer Centre, Division of Cancer Research, Medical Research Institute, University of Dundee, Dundee, DD1 9SY, Scotland (United Kingdom); Honda, Tadashi [Department of Chemistry and Institute of Chemical Biology & Drug Discovery, Stony Brook University, Stony Brook, NY, 11794 (United States); Dinkova-Kostova, Albena T., E-mail: a.dinkovakostova@dundee.ac.uk [Jacqui Wood Cancer Centre, Division of Cancer Research, Medical Research Institute, University of Dundee, Dundee, DD1 9SY, Scotland (United Kingdom); Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205 (United States); Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21205 (United States)

    2015-09-25

    The acetylenic tricyclic bis(cyanoenone) TBE-31 is a highly potent cysteine targeting compound with a reversible covalent mode of action; its best-characterized target being Kelch-like ECH-associated protein-1 (Keap1), the cellular sensor for oxidants and electrophiles. TBE-31 reacts with cysteines of Keap1, impairing its ability to target nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) for degradation. Consequently, Nrf2 accumulates and orchestrates cytoprotective gene expression. In this study we investigated the pharmacokinetic and pharmacodynamic properties of TBE-31 in C57BL/6 mice. After a single oral dose of 10 μmol/kg (∼200 nmol/animal), the concentration of TBE-31 in blood exhibited two peaks, at 22.3 nM and at 15.5 nM, 40 min and 4 h after dosing, respectively, as determined by a quantitative stable isotope dilution LC-MS/MS method. The AUC{sub 0–24h} was 195.5 h/nmol/l, the terminal elimination half-life was 10.2 h, and the k{sub el} was 0.068 h{sup −1}. To assess the pharmacodynamics of Nrf2 activation by TBE-31, we determined the enzyme activity of its prototypic target, NAD(P)H:quinone oxidoreductase 1 (NQO1) and found it elevated by 2.4- and 1.5-fold in liver and heart, respectively. Continuous feeding for 18 days with diet delivering the same daily doses of TBE-31 under conditions of concurrent treatment with the immunosuppressive agent azathioprine had a similar effect on Nrf2 activation without any indications of toxicity. Together with previous reports showing the cytoprotective effects of TBE-31 in animal models of carcinogenesis, our results demonstrate the high potency, efficacy and suitability for chronic administration of cysteine targeting reversible covalent drugs. - Highlights: • TBE-31 is a cysteine targeting compound with a reversible covalent mode of action. • After a single oral dose, the blood concentration of TBE-31 exhibits two peaks. • Oral TBE-31 is a potent activator of Nrf2-dependent enzymes in

  4. Reversal of muscle atrophy by Zhimu and Huangbai herb pair via activation of IGF-1/Akt and autophagy signal in cancer cachexia.

    Science.gov (United States)

    Zhuang, Pengwei; Zhang, Jinbao; Wang, Yan; Zhang, Mixia; Song, Lili; Lu, Zhiqiang; Zhang, Lu; Zhang, Fengqi; Wang, Jing; Zhang, Yanjun; Wei, Hongjun; Li, Hongyan

    2016-03-01

    Muscle atrophy is the prominent clinical feature of cancer-induced cachexia. Zhimu and Huangbai herb pair (ZBHP) has been used since ancient China times and have been phytochemically investigated for constituents that might cause anti-cancer, diabetes, and their complication. In this study, the effects and mechanisms of ZBHP on reversal of muscle atrophy were explored. C57BL/6 mice implanted with colon-26 adenocarcinoma were chosen to develop cancer cachexia for evaluating the effects of ZBHP on reversal of muscle atrophy. The body weight, survival time, inflammatory cytokines, and pathological changes of muscle were monitored. In addition, IGF-1/Akt and autophagy pathway members were analyzed to interpret the mechanism of drug response. The function and morphology of skeletal muscle in cachexia model were significantly disturbed, and the survival time was shortened. Consistently, inflammatory cytokines and muscle atrophy-related atrogin-1, MuRF1, and FOXO3 were significantly increased, and IGF-1/Akt and autophagy signal pathways were depressed. Treatment with ZBHP significantly alleviated tumor-free body weight reduction and cachexia-induced changes in cytokines and prolonged survival. ZBHP treatment not only inhibited the muscle atrophy-related genes but also activated the IGF-1/Akt and autophagy signal pathways to facilitate the protein synthesis. The results revealed that ZBHP treatment could inhibit the muscle atrophy induced by cancer cachexia and prolong the survival time, and ZBHP may be of value as a pharmacological alternative in treatment of cancer cachexia.

  5. Chronic ethanol intake induces partial microglial activation that is not reversed by long-term ethanol withdrawal in the rat hippocampal formation.

    Science.gov (United States)

    Cruz, Catarina; Meireles, Manuela; Silva, Susana M

    2017-05-01

    Neuroinflammation has been implicated in the pathogenesis of several disorders. Activation of microglia leads to the release of pro-inflammatory mediators and microglial-mediated neuroinflammation has been proposed as one of the alcohol-induced neuropathological mechanisms. The present study aimed to examine the effect of chronic ethanol exposure and long-term withdrawal on microglial activation and neuroinflammation in the hippocampal formation. Male rats were submitted to 6 months of ethanol treatment followed by a 2-month withdrawal period. Stereological methods were applied to estimate the total number of microglia and activated microglia detected by CD11b immunohistochemistry in the hippocampal formation. The expression levels of the pro-inflammatory cytokines TNF-α, COX-2 and IL-15 were measured by qRT-PCR. Alcohol consumption was associated with an increase in the total number of activated microglia but morphological assessment indicated that microglia did not exhibit a full activation phenotype. These data were supported by functional evidence since chronic alcohol consumption produced no changes in the expression of TNF-α or COX-2. The levels of IL-15 a cytokine whose expression is increased upon activation of both astrocytes and microglia, was induced by chronic alcohol treatment. Importantly, the partial activation of microglia induced by ethanol was not reversed by long-term withdrawal. This study suggests that chronic alcohol exposure induces a microglial phenotype consistent with partial activation without significant increase in classical cytokine markers of neuroinflammation in the hippocampal formation. Furthermore, long-term cessation of alcohol intake is not sufficient to alter the microglial partial activation phenotype induced by ethanol. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. EGCG Suppresses ERK5 Activation to Reverse Tobacco Smoke-Triggered Gastric Epithelial-Mesenchymal Transition in BALB/c Mice

    Directory of Open Access Journals (Sweden)

    Ling Lu

    2016-07-01

    Full Text Available Tobacco smoke is an important risk factor of gastric cancer. Epithelial-mesenchymal transition is a crucial pathophysiological process in cancer development. ERK5 regulation of epithelial-mesenchymal transition may be sensitive to cell types and/or the cellular microenvironment and its role in the epithelial-mesenchymal transition process remain elusive. Epigallocatechin-3-gallate (EGCG is a promising chemopreventive agent for several types of cancers. In the present study we investigated the regulatory role of ERK5 in tobacco smoke-induced epithelial-mesenchymal transition in the stomach of mice and the preventive effect of EGCG. Exposure of mice to tobacco smoke for 12 weeks reduced expression of epithelial markers E-cadherin, ZO-1, and CK5, while the expression of mesenchymal markers Snail-1, Vimentin, and N-cadherin were increased. Importantly, we demonstrated that ERK5 modulated tobacco smoke-mediated epithelial-mesenchymal transition in mice stomach, as evidenced by the findings that tobacco smoke elevated ERK5 activation, and that tobacco smoke-triggered epithelial-mesenchymal transition was reversed by ERK5 inhibition. Treatment of EGCG (100 mg/kg BW effectively attenuated tobacco smoke-triggered activation of ERK5 and epithelial-mesenchymal transition alterations in mice stomach. Collectively, these data suggested that ERK5 was required for tobacco smoke-triggered gastric epithelial-mesenchymal transition and that EGCG suppressed ERK5 activation to reverse tobacco smoke-triggered gastric epithelial-mesenchymal transition in BALB/c mice. These findings provide new insights into the mechanism of tobacco smoke-associated gastric tumorigenesis and the chemoprevention of tobacco smoke-associated gastric cancer.

  7. Supplemental feeding for ecotourism reverses diel activity and alters movement patterns and spatial distribution of the southern stingray, Dasyatis americana.

    Directory of Open Access Journals (Sweden)

    Mark J Corcoran

    Full Text Available Southern stingrays, Dasyatis americana, have been provided supplemental food in ecotourism operations at Stingray City Sandbar (SCS, Grand Cayman since 1986, with this site becoming one of the world's most famous and heavily visited marine wildlife interaction venues. Given expansion of marine wildlife interactive tourism worldwide, there are questions about the effects of such activities on the focal species and their ecosystems. We used a combination of acoustic telemetry and tag-recapture efforts to test the hypothesis that human-sourced supplemental feeding has altered stingray activity patterns and habitat use at SCS relative to wild animals at control sites. Secondarily, we also qualitatively estimated the population size of stingrays supporting this major ecotourism venue. Tag-recapture data indicated that a population of at least 164 stingrays, over 80% female, utilized the small area at SCS for prolonged periods of time. Examination of comparative movements of mature female stingrays at SCS and control sites revealed strong differences between the two groups: The fed animals demonstrated a notable inversion of diel activity, being constantly active during the day with little movement at night compared to the nocturnally active wild stingrays; The fed stingrays utilized significantly (p<0.05 smaller 24 hour activity spaces compared to wild conspecifics, staying in close proximity to the ecotourism site; Fed stingrays showed a high degree of overlap in their core activity spaces compared to wild stingrays which were largely solitary in the spaces utilized (72% vs. 3% overlap respectively. Supplemental feeding has strikingly altered movement behavior and spatial distribution of the stingrays, and generated an atypically high density of animals at SCS which could have downstream fitness costs for individuals and potentially broader ecosystem effects. These findings should help environmental managers plan mitigating measures for existing

  8. Supplemental feeding for ecotourism reverses diel activity and alters movement patterns and spatial distribution of the southern stingray, Dasyatis americana.

    Science.gov (United States)

    Corcoran, Mark J; Wetherbee, Bradley M; Shivji, Mahmood S; Potenski, Matthew D; Chapman, Demian D; Harvey, Guy M

    2013-01-01

    Southern stingrays, Dasyatis americana, have been provided supplemental food in ecotourism operations at Stingray City Sandbar (SCS), Grand Cayman since 1986, with this site becoming one of the world's most famous and heavily visited marine wildlife interaction venues. Given expansion of marine wildlife interactive tourism worldwide, there are questions about the effects of such activities on the focal species and their ecosystems. We used a combination of acoustic telemetry and tag-recapture efforts to test the hypothesis that human-sourced supplemental feeding has altered stingray activity patterns and habitat use at SCS relative to wild animals at control sites. Secondarily, we also qualitatively estimated the population size of stingrays supporting this major ecotourism venue. Tag-recapture data indicated that a population of at least 164 stingrays, over 80% female, utilized the small area at SCS for prolonged periods of time. Examination of comparative movements of mature female stingrays at SCS and control sites revealed strong differences between the two groups: The fed animals demonstrated a notable inversion of diel activity, being constantly active during the day with little movement at night compared to the nocturnally active wild stingrays; The fed stingrays utilized significantly (pecotourism site; Fed stingrays showed a high degree of overlap in their core activity spaces compared to wild stingrays which were largely solitary in the spaces utilized (72% vs. 3% overlap respectively). Supplemental feeding has strikingly altered movement behavior and spatial distribution of the stingrays, and generated an atypically high density of animals at SCS which could have downstream fitness costs for individuals and potentially broader ecosystem effects. These findings should help environmental managers plan mitigating measures for existing operations, and develop precautionary policies regarding proposed feeding sites.

  9. Superior bactericidal activity of N-bromine compounds compared to their N-chlorine analogues can be reversed under protein load.

    Science.gov (United States)

    Gottardi, W; Klotz, S; Nagl, M

    2014-06-01

    To investigate and compare the bactericidal activity (BA) of active bromine and chlorine compounds in the absence and presence of protein load. Quantitative killing tests against Escherichia coli and Staphylococcus aureus were performed both in the absence and in the presence of peptone with pairs of isosteric active chlorine and bromine compounds: hypochlorous and hypobromous acid (HOCl and HOBr), dichloro- and dibromoisocyanuric acid, chlorantine and bromantine (1,3-dibromo- and 1,3 dichloro-5,5-dimethylhydantoine), chloramine T and bromamine T (N-chloro- and N-bromo-4-methylbenzenesulphonamide sodium), and N-chloro- and N-bromotaurine sodium. To classify the bactericidal activities on a quantitative basis, an empirical coefficient named specific bactericidal activity (SBA), founded on the parameters of killing curves, was defined: SBA= mean log reductions/(mean exposure times x concentration) [mmol 1(-1) min (-1)]. In the absence of peptone, tests with washed micro-organisms revealed a throughout higher BA of bromine compounds with only slight differences between single substances. This was in contrast to chlorine compounds, whose killing times differed by a factor of more than four decimal powers. As a consequence, also the isosteric pairs showed according differences. In the presence of peptone, however, bromine compounds showed an increased loss of BA, which partly caused a reversal of efficacy within isosteric pairs. In medical practice, weakly oxidizing active chlorine compounds like chloramines have the highest potential as topical anti-infectives in the presence of proteinaceous material (mucous membranes, open wounds). Active bromine compounds, on the other hand, have their chance at insensitive body regions with low organic matter, for example skin surfaces. The expected protein load is one of the most important parameters for selection of a suited active halogen compound. © 2014 The Society for Applied Microbiology.

  10. Maternal immune activation results in complex microglial transcriptome signature in the adult offspring that is reversed by minocycline treatment

    NARCIS (Netherlands)

    Mattei, D.; Ivanov, A.; Ferrai, C.; Jordan, P.; Guneykaya, D.; Buonfiglioli, A.; Schaafsma, W.; Przanowski, P.; Deuther-Conrad, W.; Brust, P.; Hesse, S.; Patt, M.; Sabri, O.; Ross, T. L.; Eggen, B. J. L.; Boddeke, E. W. G. M.; Kaminska, B.; Beule, D.; Pombo, A.; Kettenmann, H.; Wolf, S. A.

    2017-01-01

    Maternal immune activation (MIA) during pregnancy has been linked to an increased risk of developing psychiatric pathologies in later life. This link may be bridged by a defective microglial phenotype in the offspring induced by MIA, as microglia have key roles in the development and maintenance of

  11. Proline-induced changes in acetylcholinesterase activity and gene expression in zebrafish brain: reversal by antipsychotic drugs.

    Science.gov (United States)

    Savio, L E B; Vuaden, F C; Kist, L W; Pereira, T C; Rosemberg, D B; Bogo, M R; Bonan, C D; Wyse, A T S

    2013-10-10

    Hyperprolinemia is an inherited disorder of proline metabolism and hyperprolinemic patients can present neurological manifestations, such as seizures, cognitive dysfunctions, and schizoaffective disorders. However, the mechanisms related to these symptoms are still unclear. In the present study, we evaluated the in vivo and in vitro effects of proline on acetylcholinesterase (AChE) activity and gene expression in the zebrafish brain. For the in vivo studies, animals were exposed at two proline concentrations (1.5 and 3.0mM) during 1h or 7 days (short- or long-term treatments, respectively). For the in vitro assays, different proline concentrations (ranging from 3.0 to 1000 μM) were tested. Long-term proline exposures significantly increased AChE activity for both treated groups when compared to the control (34% and 39%). Moreover, the proline-induced increase on AChE activity was completely reverted by acute administration of antipsychotic drugs (haloperidol and sulpiride), as well as the changes induced in ache expression. When assessed in vitro, proline did not promote significant changes in AChE activity. Altogether, these data indicate that the enzyme responsible for the control of acetylcholine levels might be altered after proline exposure in the adult zebrafish. These findings contribute for better understanding of the pathophysiology of hyperprolinemia and might reinforce the use of the zebrafish as a complementary vertebrate model for studying inborn errors of amino acid metabolism. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Fusing a Reversed and Informal Learning Scheme and Space: Student Perceptions of Active Learning in Physical Chemistry

    Science.gov (United States)

    Donnelly, Julie; Hernández, Florencio E.

    2018-01-01

    Physical chemistry students often have negative perceptions and low expectations for success in physical chemistry, attitudes that likely affect their performance in the course. Despite the results of several studies indicating increased positive perception of physical chemistry when active learning strategies are used, a recent survey of faculty…

  13. Identification of some factors affecting pharmaceutical active compounds (PhACs) removal in real wastewater. Case study of fungal treatment of reverse osmosis concentrate.

    Science.gov (United States)

    Badia-Fabregat, Marina; Lucas, Daniel; Gros, Meritxell; Rodríguez-Mozaz, Sara; Barceló, Damià; Caminal, Glòria; Vicent, Teresa

    2015-01-01

    Many technologies are being developed for the efficient removal of micropollutants from wastewater and, among them, fungal degradation is one of the possible alternative biological treatments. In this article, some factors that might affect pharmaceutically active compounds (PhACs) removal in a fungal treatment of real wastewater were identified in batch bioreactor treating reverse osmosis concentrate (ROC) from urban wastewater treatment plant (WWTP). We found that degradation of PhACs by Trametes versicolor was enhanced by addition of external nutrients (global removal of 44%). Moreover, our results point out that high aeration might be involved in the increase in the concentration of some PhACs. In fact, conjugation and deconjugation processes (among others) affect the removal assessment of emerging contaminants when working with real concentrations in comparison to experiments with spiked samples. Moreover, factors that could affect the quantification of micropollutants at lab-scale experiments were studied. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Fenproporex increases locomotor activity and alters energy metabolism, and mood stabilizers reverse these changes: a proposal for a new animal model of mania.

    Science.gov (United States)

    Rezin, Gislaine T; Furlanetto, Camila B; Scaini, Giselli; Valvassori, Samira S; Gonçalves, Cinara L; Ferreira, Gabriela K; Jeremias, Isabela C; Resende, Wilson R; Cardoso, Mariane R; Varela, Roger B; Quevedo, João; Streck, Emilio L

    2014-04-01

    Fenproporex (Fen) is converted in vivo into amphetamine, which is used to induce mania-like behaviors in animals. In the present study, we intend to present a new animal model of mania. In order to prove through face, construct, and predictive validities, we evaluated behavioral parameters (locomotor activity, stereotypy activity, and fecal boli amount) and brain energy metabolism (enzymes citrate synthase; malate dehydrogenase; succinate dehydrogenase; complexes I, II, II-III, and IV of the mitochondrial respiratory chain; and creatine kinase) in rats submitted to acute and chronic administration of fenproporex, treated with lithium (Li) and valproate (VPA). The administration of Fen increased locomotor activity and decreased the activity of Krebs cycle enzymes, mitochondrial respiratory chain complexes, and creatine kinase, in most brain structures evaluated. In addition, treatment with mood stabilizers prevented and reversed this effect. Our results are consistent with the literature that demonstrates behavioral changes and mitochondrial dysfunction caused by psychostimulants. These findings suggest that chronic administration of Fen may be a potential animal model of mania.

  15. Tuning the Stability of Organic Active Materials for Nonaqueous Redox Flow Batteries via Reversible, Electrochemically Mediated Li + Coordination

    Energy Technology Data Exchange (ETDEWEB)

    Carino, Emily V.; Staszak-Jirkovsky, Jakub; Assary, Rajeev S.; Curtiss, Larry A.; Markovic, Nenad M.; Brushett, Fikile R.

    2016-03-24

    We describe an electrochemically mediated interaction between Li+ and a promising active material for nonaqueous redox flow batteries (RFBs), 1,2,3,4-tetrahydro-6,7-dimethoxy-1,1,4,4-tetramethylnaphthalene (TDT), and the impact of this structural interaction on material stability during voltammetric cycling. TDT could be an advantageous organic positive electrolyte material for nonaqueous RFBs due to its high oxidation potential, 4.21 V vs Li/Li+, and solubility of at least 1.0 M in select electrolytes. Although results from voltammetry suggest TDT displays Nernstian reversibility in many nonaqueous electrolyte solutions, bulk electrolysis reveals significant degradation in all electrolytes studied, the extent of which depends on the electrolyte solution composition. Results of subtractively normalized in situ Fourier transform infrared spectroscopy (SNIFTIRS) confirm that TDT undergoes reversible structural changes during cyclic voltammetry in propylene carbonate and 1,2-dimethoxyethane solutions containing Li+ electrolytes, but irreversible degradation occurs when tetrabutylammonium (TBA+) replaces Li+ as the electrolyte cation in these solutions. By combining the results from SNIFTIRS experiments with calculations from density functional theory, solution-phase active species structure and potential-dependent interactions can be determined. We find that Li+ coordinates to the Lewis basic methoxy groups of neutral TDT and, upon electrochemical oxidation, this complex dissociates into the radical cation TDT•+ and Li+. The improved cycling stability in the presence of Li+ relative to TBA+ suggests that the structural interaction reported herein may be advantageous to the design of energy storage materials based on organic molecules.

  16. Distinct neuronal activation patterns are associated with PCP-induced social withdrawal and its reversal by the endocannabinoid-enhancing drug URB597.

    Science.gov (United States)

    Matricon, Julien; Seillier, Alexandre; Giuffrida, Andrea

    2016-09-01

    The fatty acid amide hydrolase inhibitor, URB597, an endocannabinoid enhancing drug, reverses social withdrawal in the sub-chronic PCP rat model of schizophrenia, but reduces social interaction (SI) in controls. To identify the anatomical substrates associated with PCP-induced social withdrawal and the contrasting effects of URB597 on SI in PCP- versus saline-treated rats, we analyzed SI-induced c-Fos expression in 28 brain areas relevant to schizophrenia and/or social behavior following vehicle or URB597 administration. In saline-treated rats, SI was accompanied by changes in c-Fos expression in the infralimbic and orbitofrontal cortices, dorsomedial caudate putamen, ventrolateral nucleus of the septum, dorsolateral periaqueductal gray (dlPAG) and central amygdala. Except for the dlPAG, these changes were not observed in PCP-treated rats or in saline-treated rats receiving URB597. In the dorsomedial part of the bed nucleus of the stria terminalis (dmBNST), SI-induced c-Fos expression was observed only in PCP-treated rats. Interestingly, URB597 in PCP-treated rats restored a similar c-Fos expression pattern as observed in saline-treated rats: activation of the orbitofrontal cortex, inhibition of the central amygdala and suppression of activation of the dmBNST. These data suggest that orbitofrontal cortex, central amygdala and dmBNST play a critical role in the reversal of PCP-induced social withdrawal by URB597. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  17. Reversible reprotoxic effects of manganese through DAF-16 transcription factor activation and vitellogenin downregulation in Caenorhabditis elegans.

    Science.gov (United States)

    Gubert, Priscila; Puntel, Bruna; Lehmen, Tassia; Bornhorst, Julia; Avila, Daiana S; Aschner, Michael; Soares, Felix A A

    2016-04-15

    Vitellogenesis is the yolk production process which provides the essential nutrients for the developing embryos. Yolk is a lipoprotein particle that presents lipids and lipid-binding proteins, referred to as vitellogenins (VIT). The Caenorhabditis elegans nematode has six genes encoding VIT lipoproteins. Several pathways are known to regulate vitellogenesis, including the DAF-16 transcription factor. Some reports have shown that heavy metals, such as manganese (Mn), impair brood size in C. elegans; however the mechanisms associated with this effect have yet to be identified. Our aim was to evaluate Mn's effects on C. elegans reproduction and better understand the pathways related to these effects. Young adult larval stage worms were treated for 4h with Mn in 85mM NaCl and Escherichia coli OP50 medium. Mn reduced egg-production and egg-laying during the first 24h after the treatment, although the total number of progenies were indistinguishable from the control group levels. This delay may have occurred due to DAF-16 activation, which was noted only after the treatment and was not apparent 24h later. Moreover, the expression, protein levels and green fluorescent protein (GFP) fluorescence associated with VIT were decreased soon after Mn treatment and recovered after 24h. Combined, these data suggest that the delay in egg-production is likely regulated by DAF-16 and followed by the inhibition of VIT transport activity. Further studies are needed to clarify the mechanisms associated with Mn-induced DAF-16 activation. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Design, Synthesis and Biological Activity of Novel Reversible Peptidyl FVIIa Inhibitors Rh-Catalyzed Enantioselective Synthesis of Diaryl Amines

    DEFF Research Database (Denmark)

    Storgaard, Morten

    functional group tolerance. Unfortunately, these -aryl tetramic acids were too unreactive and ring opening toward the synthesis of the building block did not succeed. However, -aryl tetramic acids are still interesting compounds due to their potential biological activity. The building block 3.15 (P1......-catalyzed enantioselective synthesis of diaryl amines, which is an important class of compounds (Chapter 4). For example it is found in the third generation anti-histaminic agent levocetirizine. Development of efficient synthetic routes is therefore of considerably interest. The rhodium-catalyzed enantioselective synthesis...

  19. Reverse Catastrophe

    Directory of Open Access Journals (Sweden)

    Przemysław Czapliński

    2015-01-01

    Full Text Available The principal notion of the article–a “backward catastrophe”– stands for a catastrophe which occurs unseen until it becomes recognized and which broadens its destructive activity until it has been recognized. This concept in the article has been referred to the Shoah. The main thesis is that the recognition of the actual influence of the Holocaust began in Polish culture in the mid-1980s (largely it started with the film by Claude Lanzmann Shoah and the essay by Jan Błoński Biedni Polacy patrzą na getto [“The Poor Poles Look at the Ghetto”], that is when the question: “What happened to the Jews”, assumes the form: “Did the things that happened to the Jews, also happened to the Poles?”. Cognitive and ethical reorientation leads to the revealing of the hidden consequences of the Holocaust reaching as far as the present day and undermining the foundations of collective identity. In order to understand this situation (and adopt potentially preventive actions Polish society should be recognized as a postcatastrophic one.

  20. Gamma ray sterilization of delta inulin adjuvant particles (Advax™) makes minor, partly reversible structural changes without affecting adjuvant activity

    Science.gov (United States)

    Cooper, P. D.; Barclay, T. G.; Ginic-Markovic, M.; Petrovsky, N.

    2014-01-01

    We earlier identified a developmental series of seven isoforms/polymorphs of microparticulate inulin by comparing non-covalent bonding strengths. Their pharmaceutical utility lies in modulation of cellular immunity, exploited as vaccine adjuvants (Advax™) especially for delta inulin (DI). As such particles cannot be sterilized by filtration we explore the effect of 60Co gamma radiation (GR) on inulin isoforms, particularly DI. Its adjuvant activity and overt physical properties were unaffected by normal GR sterilizing doses (up to 25 kGy). Heating irradiated isoform suspensions near their critical dissolution temperature revealed increased solubility deduced to reflect a single lethal event in one component of a multi-component structure. Local oxidative effects of GR on DI were not found. The observed DI loss was almost halved by re-annealing at the critical temperature: surviving inulin chains apparently reassemble into smaller amounts of the original type of structure. Colorimetric tetrazolium assay revealed increases in reducing activity after GR of raw inulin powder, which yielded DI with normal physical properties but only 25% normal recovery yet 4× normal reducing ability, implying final retention of some GR-changed inulin chains. These findings suggest minimal inulin chain cleavage and confirm that GR may be a viable strategy for terminal sterilization of microparticulate inulin adjuvants. PMID:24342245

  1. Zinc-phosphate nanoparticles with reversibly attached TNF-α analogs: an interesting concept for potential use in active immunotherapy

    International Nuclear Information System (INIS)

    Hribar, Gorazd; Žnidaršič, Andrej; Bele, Marjan; Maver, Uroš; Caserman, Simon; Gaberšček, Miran; Gaberc-Porekar, Vladka

    2011-01-01

    The authors’ intention was to prepare nanometer-sized zinc-phosphate nanoparticles that would be capable of binding histidine-rich TNF-α analogs onto their surface via a coordinative bond. Zinc-phosphate nanoparticles with a size of around 60 nm were prepared by a wet precipitation method and characterized using SEM, EDX, XRD, and DLS. First, BSA was bound as a testing protein, afterward two TNF-α analogs with decreased activity were bound to the described nanoparticles. The efficiency of binding and the existence of coordinative bond were confirmed with SDS-PAGE analysis. During binding, particle storage, and release experiments, the prepared TNF-α analogs retained their biological activity—hence the epitopes necessary for formation of antibodies stayed intact. The particle size did not change within a period of 2 weeks. No significant agglomeration was observed, the particles could be quickly dispersed in ultrasound. The present nanoparticles and the general approach of coordinative binding are widely applicable for natural and engineered histidine-rich proteins. The nanoparticles bearing appropriate TNF-α analogs could also be potentially used for active immunotherapy to tackle the chronic inflammatory diseases associated with pathogenically elevated levels of TNF-α.

  2. Effects of CPAP-therapy on brain electrical activity in obstructive sleep apneic patients: a combined EEG study using LORETA and Omega complexity : reversible alterations of brain activity in OSAS.

    Science.gov (United States)

    Toth, Marton; Faludi, Bela; Kondakor, Istvan

    2012-10-01

    Effects of initiation of continuous positive airway pressure (CPAP) therapy on EEG background activity were investigated in patients with obstructive sleep apnea syndrome (OSAS, N = 25) to test possible reversibility of alterations of brain electrical activity caused by chronic hypoxia. Normal control group (N = 14) was also examined. Two EEG examinations were done in each groups: at night and in the next morning. Global and regional (left vs. right, anterior vs. posterior) measures of spatial complexity (Omega complexity) were used to characterize the degree of spatial synchrony of EEG. Low resolution electromagnetic tomography (LORETA) was used to localize generators of EEG activity in separate frequency bands. Before CPAP-treatment, a significantly lower Omega complexity was found globally and over the right hemisphere. Due to CPAP-treatment, these significant differences vanished. Significantly decreased Omega complexity was found in the anterior region after treatment. LORETA showed a decreased activity in all of the beta bands after therapy in the right hippocampus, premotor and temporo-parietal cortex, and bilaterally in the precuneus, paracentral and posterior cingulate cortex. No significant changes were seen in control group. Comparing controls and patients before sleep, an increased alpha2 band activity was seen bilaterally in the precuneus, paracentral and posterior cingulate cortex, while in the morning an increased beta3 band activity in the left precentral and bilateral premotor cortex and a decreased delta band activity in the right temporo-parietal cortex and insula were observed. These findings indicate that effect of sleep on EEG background activity is different in OSAS patients and normal controls. In OSAS patients, significant changes lead to a more normal EEG after a night under CPAP-treatment. Compensatory alterations of brain electrical activity in regions associated with influencing sympathetic outflow, visuospatial abilities, long

  3. Structure-based design, synthesis, and biological evaluation of novel pyrrolyl aryl sulfones: HIV-1 non-nucleoside reverse transcriptase inhibitors active at nanomolar concentrations.

    Science.gov (United States)

    Artico, M; Silvestri, R; Pagnozzi, E; Bruno, B; Novellino, E; Greco, G; Massa, S; Ettorre, A; Loi, A G; Scintu, F; La Colla, P

    2000-05-04

    Pyrrolyl aryl sulfones (PASs) have been recently reported as a new class of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) inhibitors acting at the non-nucleoside binding site of this enzyme (Artico, M.; et al. J. Med. Chem. 1996, 39, 522-530). Compound 3, the most potent inhibitor within the series (EC(50) = 0.14 microM, IC(50) = 0.4 microM, and SI > 1429), was then selected as a lead compound for a synthetic project based on molecular modeling studies. Using the three-dimensional structure of RT cocrystallized with the alpha-APA derivative R95845, we derived a model of the RT/3 complex by taking into account previously developed structure-activity relationships. Inspection of this model and docking calculations on virtual compounds prompted the design of novel PAS derivatives and related analogues. Our computational approach proved to be effective in making qualitative predictions, that is in discriminating active versus inactive compounds. Among the compounds synthesized and tested, 20 was the most active one, with EC(50) = 0.045 microM, IC(50) = 0.05 microM, and SI = 5333. Compared with the lead 3, these values represent a 3- and 8-fold improvement in the cell-based and enzyme assays, respectively, together with the highest selectivity achieved so far in the PAS series.

  4. Deep reversible storage. Design options for the storage in deep geological formation - High-medium activity, long living wastes 2009 milestone

    International Nuclear Information System (INIS)

    2010-09-01

    This report aims at presenting a synthesis of currently studied solutions for the different components of the project of deep geological radioactive waste storage centre. For each of these elements, the report indicates the main operational objectives to be taken into account in relationship with safety functions or with reversibility. It identifies the currently proposed design options, presents the technical solutions (with sometime several possibilities), indicates industrial references (in the nuclear sector, in underground works) and comments results of technological tests performed by the ANDRA. After a description of functionalities and of the overall organisation of storage components, the different following elements and aspects are addressed: surface installations, underground architecture, parcel transfer between the surface and storage cells, storage container for medium-activity long-life (MAVL) waste, storage cell for medium-activity long-life waste, handling of MAVL parcels in storage cells, storage container for high-activity (HA) waste, storage cell for HA waste, handling of HA parcels in storage cells, and works for site closing

  5. Magnesium Inhibits Wnt/β-Catenin Activity and Reverses the Osteogenic Transformation of Vascular Smooth Muscle Cells

    Science.gov (United States)

    Montes de Oca, Addy; Guerrero, Fatima; Martinez-Moreno, Julio M.; Madueño, Juan A.; Herencia, Carmen; Peralta, Alan; Almaden, Yolanda; Lopez, Ignacio; Aguilera-Tejero, Escolastico; Gundlach, Kristina; Büchel, Janine; Peter, Mirjam E.; Passlick-Deetjen, Jutta; Rodriguez, Mariano; Muñoz-Castañeda, Juan R.

    2014-01-01

    Magnesium reduces vascular smooth muscle cell (VSMC) calcification in vitro but the mechanism has not been revealed so far. This work used only slightly increased magnesium levels and aimed at determining: a) whether inhibition of magnesium transport into the cell influences VSMC calcification, b) whether Wnt/β-catenin signaling, a key mediator of osteogenic differentiation, is modified by magnesium and c) whether magnesium can influence already established vascular calcification. Human VSMC incubated with high phosphate (3.3 mM) and moderately elevated magnesium (1.4 mM) significantly reduced VSMC calcification and expression of the osteogenic transcription factors Cbfa-1 and osterix, and up-regulated expression of the natural calcification inhibitors matrix Gla protein (MGP) and osteoprotegerin (OPG). The protective effects of magnesium on calcification and expression of osteogenic markers were no longer observed in VSMC cultured with an inhibitor of cellular magnesium transport (2-aminoethoxy-diphenylborate [2-APB]). High phosphate induced activation of Wnt/β-catenin pathway as demonstrated by the translocation of β-catenin into the nucleus, increased expression of the frizzled-3 gene, and downregulation of Dkk-1 gene, a specific antagonist of the Wnt/β-catenin signaling pathway. The addition of magnesium however inhibited phosphate-induced activation of Wnt/β-catenin signaling pathway. Furthermore, TRPM7 silencing using siRNA resulted in activation of Wnt/β-catenin signaling pathway. Additional experiments were performed to test the ability of magnesium to halt the progression of already established VSMC calcification in vitro. The delayed addition of magnesium decreased calcium content, down-regulated Cbfa-1 and osterix and up-regulated MGP and OPG, when compared with a control group. This effect was not observed when 2-APB was added. In conclusion, magnesium transport through the cell membrane is important to inhibit VSMC calcification in vitro

  6. Size Control of Iron Oxide Nanoparticles Using Reverse Microemulsion Method: Morphology, Reduction, and Catalytic Activity in CO Hydrogenation

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Housaindokht

    2013-01-01

    Full Text Available Iron oxide nanoparticles were prepared by microemulsion method and evaluated in Fischer-Tropsch synthesis. The precipitation process was performed in a single-phase microemulsion operating region. Different HLB values of surfactant were prepared by mixing of sodium dodecyl sulfate (SDS and Triton X-100. Transmission electron microscopy (TEM, surface area, pore volume, average pore diameter, pore size distribution, and XRD patterns were used to analyze size distribution, shape, and structure of precipitated hematite nanoparticles. Furthermore, temperature programmed reduction (TPR and catalytic activity in CO hydrogenation were implemented to assess the performance of the samples. It was found that methane and CO2 selectivity and also the syngas conversion increased as the HLB value of surfactant decreased. In addition, the selectivity to heavy hydrocarbons and chain growth probability (α decreased by decreasing the catalyst crystal size.

  7. Serotonin/dopamine interactions in a hyperactive mouse: reduced serotonin receptor 1B activity reverses effects of dopamine transporter knockout.

    Directory of Open Access Journals (Sweden)

    Frank Scott Hall

    Full Text Available Knockout (KO mice that lack the dopamine transporter (SL6A3; DAT display increased locomotion that can be attenuated, under some circumstances, by administration of drugs that normally produce psychostimulant-like effects, such as amphetamine and methylphenidate. These results have led to suggestions that DAT KO mice may model features of attention deficit hyperactivity disorder (ADHD and that these drugs may act upon serotonin (5-HT systems to produce these unusual locomotor decreasing effects. Evidence from patterns of brain expression and initial pharmacologic studies led us to use genetic and pharmacologic approaches to examine the influence of altered 5-HT1B receptor activity on hyperactivity in DAT KO mice. Heterozygous 5-HT1B KO and pharmacologic 5-HT1B antagonism both attenuated locomotor hyperactivity in DAT KO mice. Furthermore, DAT KO mice with reduced, but not eliminated, 5-HT1B receptor expression regained cocaine-stimulated locomotion, which was absent in DAT KO mice with normal levels of 5-HT1B receptor expression. Further experiments demonstrated that the degree of habituation to the testing apparatus determined whether cocaine had no effect on locomotion in DAT KO or reduced locomotion, helping to resolve differences among prior reports. These findings of complementation of the locomotor effects of DAT KO by reducing 5-HT1B receptor activity underscore roles for interactions between specific 5-HT receptors and dopamine (DA systems in basal and cocaine-stimulated locomotion and support evaluation of 5-HT1B antagonists as potential, non-stimulant ADHD therapeutics.

  8. The Vaccinium corymbosum FLOWERING LOCUS T-like gene (VcFT): a flowering activator reverses photoperiodic and chilling requirements in blueberry.

    Science.gov (United States)

    Song, Guo-qing; Walworth, Aaron; Zhao, Dongyan; Jiang, Ning; Hancock, James F

    2013-11-01

    The blueberry FLOWERING LOCUS T ( FT )-like gene ( VcFT ) cloned from the cDNA of a tetraploid, northern highbush blueberry ( Vaccinium corymbosum L.) is able to reverse the photoperiodic and chilling requirements and drive early and continuous flowering. Blueberry is a woody perennial bush with a longer juvenile period than annual crops, requiring vernalization to flower normally. Few studies have been reported on the molecular mechanism of flowering in blueberry or other woody plants. Because FLOWERING LOCUS T (FT) from Arabidopsis thaliana plays a multifaceted role in generating mobile molecular signals to regulate plant flowering time, isolation and functional analysis of the blueberry (Vaccinium corymbosum L.) FT-like gene (VcFT) will facilitate the elucidation of molecular mechanisms of flowering in woody plants. Based on EST sequences, a 525-bpVcFT was identified and cloned from the cDNA of a tetraploid, northern highbush blueberry cultivar, Bluecrop. Ectopic expression of 35S:VcFT in tobacco induced flowering an average of 28 days earlier than wild-type plants. Expression of the 35S:VcFT in the blueberry cultivar Aurora resulted in an extremely early flowering phenotype, which flowered not only during in vitro culture, a growth stage when nontransgenic shoots had not yet flowered, but also in 6-10-week old, soil-grown transgenic plants, in contrast to the fact that at least 1 year and 800 chilling hours are required for the appearance of the first flower of both nontransgenic 'Aurora' and transgenic controls with the gusA. These results demonstrate that the VcFT is a functional floral activator and overexpression of the VcFT is able to reverse the photoperiodic and chilling requirements and drive early and continuous flowering.

  9. Reversal Strategies for NOACs

    DEFF Research Database (Denmark)

    Husted, Steen; Verheugt, Freek; Comuth, Willemijn

    2015-01-01

    , coagulation factor concentrates or NOAC-specific antidotes could be used. Coagulation factor concentrates can be used in patients with haemophilia and to reverse the effect of VKAs but, in NOAC-treated patients, results are inconsistent and these agents could potentially have pro-thrombotic effects. Specific...... antidotes for NOACs are expected to be on the market soon. Phase III clinical trials with a humanized antibody fragment directed against dabigatran (idarucizumab) and recombinant, modified factor Xa (andexanet alfa) are ongoing. A molecule (aripazine) with broad activity against various anticoagulants...

  10. High sensitive RNA detection by one-step RT-PCR using the genetically engineered variant of DNA polymerase with reverse transcriptase activity from hyperthermophilies.

    Science.gov (United States)

    Okano, Hiroyuki; Baba, Misato; Kawato, Katsuhiro; Hidese, Ryota; Yanagihara, Itaru; Kojima, Kenji; Takita, Teisuke; Fujiwara, Shinsuke; Yasukawa, Kiyoshi

    2018-03-01

    One-step RT-PCR has not been widely used even though some thermostable DNA polymerases with reverse transcriptase (RT) activity were developed from bacterial and archaeal polymerases, which is owing to low cDNA synthesis activity from RNA. In the present study, we developed highly-sensitive one-step RT-PCR using the single variant of family A DNA polymerase with RT activity, K4pol L329A (L329A), from the hyperthermophilic bacterium Thermotoga petrophila K4 or the 16-tuple variant of family B DNA polymerase with RT activity, RTX, from the hyperthermophilic archaeon Thermococcus kodakarensis. Optimization of reaction condition revealed that the activities for cDNA synthesis and PCR of K4pol L329A and RTX were highly affected by the concentrations of MgCl 2 and Mn(OCOCH 3 ) 2 as well as those of K4pol L329A or RTX. Under the optimized condition, 300 copies/μl of target RNA in 10 μl reaction volumes were successfully detected by the one-step RT-PCR with K4pol L329A or RTX, which was almost equally sensitive enough compared with the current RT-PCR condition using retroviral RT and thermostable DNA polymerase. Considering that K4pol L329A and RTX are stable even at 90-100°C, our results suggest that the one-step RT-PCR with K4pol L329A or RTX is more advantageous than the current one. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  11. Non-surface activity and micellization behavior of cationic amphiphilic block copolymer synthesized by reversible addition-fragmentation chain transfer process.

    Science.gov (United States)

    Ghosh, Arjun; Yusa, Shin-ichi; Matsuoka, Hideki; Saruwatari, Yoshiyuki

    2011-08-02

    Cationic amphiphilic diblock copolymers of poly(n-butylacrylate)-b-poly(3-(methacryloylamino)propyl)trimethylammonium chloride) (PBA-b-PMAPTAC) with various hydrophobic and hydrophilic chain lengths were synthesized by a reversible addition-fragmentation chain transfer (RAFT) process. Their molecular characteristics such as surface activity/nonactivity were investigated by surface tension measurements and foam formation observation. Their micelle formation behavior and micelle structure were investigated by fluorescence probe technique, static and dynamic light scattering (SLS and DLS), etc., as a function of hydrophilic and hydrophobic chain lengths. The block copolymers were found to be non-surface active because the surface tension of the aqueous solutions did not change with increasing polymer concentration. Critical micelle concentration (cmc) of the polymers could be determined by fluorescence and SLS measurements, which means that these polymers form micelles in bulk solution, although they were non-surface active. Above the cmc, the large blue shift of the emission maximum of N-phenyl-1-naphthylamine (NPN) probe and the low micropolarity value of the pyrene probe in polymer solution indicate the core of the micelle is nonpolar in nature. Also, the high value of the relative intensity of the NPN probe and the fluorescence anisotropy of the 1,6-diphenyl-1,3,5-hexatriene (DPH) probe indicated that the core of the micelle is highly viscous in nature. DLS was used to measure the average hydrodynamic radii and size distribution of the copolymer micelles. The copolymer with the longest PBA block had the poorest water solubility and consequently formed micelles with larger size while having a lower cmc. The "non-surface activity" was confirmed for cationic amphiphilic diblock copolymers in addition to anionic ones studied previously, indicating the universality of non-surface activity nature.

  12. Reversible blockade of complex I or inhibition of PKCβ reduces activation and mitochondria translocation of p66Shc to preserve cardiac function after ischemia.

    Directory of Open Access Journals (Sweden)

    Meiying Yang

    Full Text Available Excess mitochondrial reactive oxygen species (mROS play a vital role in cardiac ischemia reperfusion (IR injury. P66Shc, a splice variant of the ShcA adaptor protein family, enhances mROS production by oxidizing reduced cytochrome c to yield H2O2. Ablation of p66Shc protects against IR injury, but it is unknown if and when p66Shc is activated during cardiac ischemia and/or reperfusion and if attenuating complex I electron transfer or deactivating PKCβ alters p66Shc activation during IR is associated with cardioprotection.Isolated guinea pig hearts were perfused and subjected to increasing periods of ischemia and reperfusion with or without amobarbital, a complex I blocker, or hispidin, a PKCβ inhibitor. Phosphorylation of p66Shc at serine 36 and levels of p66Shc in mitochondria and cytosol were measured. Cardiac functional variables and redox states were monitored online before, during and after ischemia. Infarct size was assessed in some hearts after 120 min reperfusion.Phosphorylation of p66Shc and its translocation into mitochondria increased during reperfusion after 20 and 30 min ischemia, but not during ischemia only, or during 5 or 10 min ischemia followed by 20 min reperfusion. Correspondingly, cytosolic p66Shc levels decreased during these ischemia and reperfusion periods. Amobarbital or hispidin reduced phosphorylation of p66Shc and its mitochondrial translocation induced by 30 min ischemia and 20 min reperfusion. Decreased phosphorylation of p66Shc by amobarbital or hispidin led to better functional recovery and less infarction during reperfusion.Our results show that IR activates p66Shc and that reversible blockade of electron transfer from complex I, or inhibition of PKCβ activation, decreases p66Shc activation and translocation and reduces IR damage. These observations support a novel potential therapeutic intervention against cardiac IR injury.

  13. Impaired transcriptional activity of Nrf2 in age-related myocardial oxidative stress is reversible by moderate exercise training.

    Directory of Open Access Journals (Sweden)

    Sellamuthu S Gounder

    Full Text Available Aging promotes accumulation of reactive oxygen/nitrogen species (ROS/RNS in cardiomyocytes, which leads to contractile dysfunction and cardiac abnormalities. These changes may contribute to increased cardiovascular disease in the elderly. Inducible antioxidant pathways are regulated by nuclear erythroid 2 p45-related factor 2 (Nrf2 through antioxidant response cis-elements (AREs and are impaired in the aging heart. Whereas acute exercise stress (AES activates Nrf2 signaling and promotes myocardial antioxidant function in young mice (~2 months, aging mouse (>23 months hearts exhibit significant oxidative stress as compared to those of the young. The purpose of this study was to investigate age-dependent regulation of Nrf2-antioxidant mechanisms and redox homeostasis in mouse hearts and the impact of exercise. Old mice were highly susceptible to oxidative stress following high endurance exercise stress (EES, but demonstrated increased adaptive redox homeostasis after moderate exercise training (MET; 10m/min, for 45 min/day for ~6 weeks. Following EES, transcription and protein levels for most of the ARE-antioxidants were increased in young mice but their induction was blunted in aging mice. In contrast, 6-weeks of chronic MET promoted nuclear levels of Nrf2 along with its target antioxidants in the aging heart to near normal levels as seen in young mice. These observations suggest that enhancing Nrf2 function and endogenous cytoprotective mechanisms by MET, may combat age-induced ROS/RNS and protect the myocardium from oxidative stress diseases.

  14. Managing Reverse Logistics or Reversing Logistics Management?

    OpenAIRE

    Brito, Marisa

    2004-01-01

    textabstractIn the past, supply chains were busy fine-tuning the logistics from raw material to the end customer. Today an increasing flow of products is going back in the chain. Thus, companies have to manage reverse logistics as well.This thesis contributes to a better understanding of reverse logistics. The thesis brings insights on reverse logistics decision-making and it lays down theoretical principles for reverse logistics as a research field.In particular it puts together a framework ...

  15. Enhanced activity of carbosilane dendrimers against HIV when combined with reverse transcriptase inhibitor drugs: searching for more potent microbicides

    Directory of Open Access Journals (Sweden)

    Vacas-Córdoba E

    2014-07-01

    Full Text Available Enrique Vacas-Córdoba,1–3 Marta Galán,3,4 Francisco J de la Mata,3,4 Rafael Gómez,3,4 Marjorie Pion,1–3 M Ángeles Muñoz-Fernández1–3 1Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain; 2Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain; 3Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, (CIBER-BBN, Madrid, Spain; 4Dendrimers for Biomedical Applications Group (BioInDen, University of Alcalá, Madrid, Spain Abstract: Self-administered topical microbicides or oral preexposure prophylaxis could be very helpful tools for all risk groups to decrease the human immunodeficiency virus (HIV-1 infection rates. Up until now, antiretrovirals (ARVs have been the most advanced microbicide candidates. Nevertheless, the majority of clinical trials has failed in HIV-1 patients. Nanotechnology offers suitable approaches to develop novel antiviral agents. Thereby, new nanosystems, such as carbosilane dendrimers, have been shown to be safe and effective compounds against HIV with great potential as topical microbicides. In addition, because most of the attempts to develop effective topical microbicides were unsuccessful, combinatorial strategies could be a valid approach when designing new microbicides. We evaluated various combinations of anionic carbosilane dendrimers with sulfated (G3-S16 and naphthyl sulfonated (G2-NF16 ended groups with different ARVs against HIV-1 infection. The G3-S16 and G2-NF16 dendrimers showed a synergistic or additive activity profile with zidovudine, efavirenz, and tenofovir in the majority of the combinations tested against the X4 and R5 tropic HIV-1 in cell lines, as well as in human primary cells. Therefore, the combination of ARVs and polyanionic carbosilane dendrimers enhances the antiviral potency of the individual compounds, and our findings support further clinical research on combinational approaches as

  16. Biogenic nanosilver incorporated reverse osmosis membrane for antibacterial and antifungal activities against selected pathogenic strains: an enhanced eco-friendly water disinfection approach.

    Science.gov (United States)

    Manjumeena, R; Duraibabu, D; Sudha, J; Kalaichelvan, P T

    2014-01-01

    Reverse osmosis (RO) membranes have been used extensively in water desalination plants, waste water treatment in industries, agricultural farms and drinking water production applications. The objective of this work is to impart antibacterial and antifungal activities to commercially available RO membrane used in water purification systems by incorporating biogenic silver nanoparticles(AgNPs) synthesized using Rosa indica wichuriana hybrid leaf extract. The morphology and surface topography of uncoated and AgNPs-coated RO membrane were studied using Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM). Elemental composition of the AgNPs-coated RO membrane was analyzed by energy-dispersive X-ray spectroscopy (EDAX). The functional groups were identified by Fourier Transform Infrared spectroscopy (FT-IR). Hydrophilicity of the uncoated and AgNPs-coated RO membrane was analyzed using water contact angle measurements. The thermal properties were studied by thermogravimetric analysis (TGA). The AgNPs incorporated RO membrane exhibited good antibacterial and antifungal activities against pathogenic bacterial strains such as E. coli, S. aureus, M. luteus, K. pneumoniae, and P. aeruginosa and fungal strains such as Candida tropicalis, C. krusei, C. glabrata, and C. albicans.

  17. c-Kit-positive cardiac stem cells nested in hypoxic niches are activated by stem cell factor reversing the aging myopathy.

    Science.gov (United States)

    Sanada, Fumihiro; Kim, Junghyun; Czarna, Anna; Chan, Noel Yan-Ki; Signore, Sergio; Ogórek, Barbara; Isobe, Kazuya; Wybieralska, Ewa; Borghetti, Giulia; Pesapane, Ada; Sorrentino, Andrea; Mangano, Emily; Cappetta, Donato; Mangiaracina, Chiara; Ricciardi, Mario; Cimini, Maria; Ifedigbo, Emeka; Perrella, Mark A; Goichberg, Polina; Choi, Augustine M; Kajstura, Jan; Hosoda, Toru; Rota, Marcello; Anversa, Piero; Leri, Annarosa

    2014-01-03

    Hypoxia favors stem cell quiescence, whereas normoxia is required for stem cell activation, but whether cardiac stem cell (CSC) function is regulated by the hypoxic/normoxic state of the cell is currently unknown. A balance between hypoxic and normoxic CSCs may be present in the young heart, although this homeostatic control may be disrupted with aging. Defects in tissue oxygenation occur in the old myocardium, and this phenomenon may expand the pool of hypoxic CSCs, which are no longer involved in myocyte renewal. Here, we show that the senescent heart is characterized by an increased number of quiescent CSCs with intact telomeres that cannot re-enter the cell cycle and form a differentiated progeny. Conversely, myocyte replacement is controlled only by frequently dividing CSCs with shortened telomeres; these CSCs generate a myocyte population that is chronologically young but phenotypically old. Telomere dysfunction dictates their actual age and mechanical behavior. However, the residual subset of quiescent young CSCs can be stimulated in situ by stem cell factor reversing the aging myopathy. Our findings support the notion that strategies targeting CSC activation and growth interfere with the manifestations of myocardial aging in an animal model. Although caution has to be exercised in the translation of animal studies to human beings, our data strongly suggest that a pool of functionally competent CSCs persists in the senescent heart and that this stem cell compartment can promote myocyte regeneration effectively, partly correcting the aging myopathy.

  18. Reduced Activity of SRY and its Target Enhancer Sox9-TESCO in a Mouse Species with X*Y Sex Reversal.

    Science.gov (United States)

    Zhao, Liang; Quinn, Alexander; Ng, Ee Ting; Veyrunes, Frederic; Koopman, Peter

    2017-02-03

    In most eutherian mammals, sex determination is governed by the Y-linked gene Sry, but in African pygmy mice Mus minutoides, Sry action is overridden by a variant X chromosome (X*), yielding X*Y females. We hypothesized that X*Y sex reversal may be underpinned not only by neomorphic X chromosome functionality, but also by a compromised Sry pathway. Here, we show that neither M. minutoides SRY nor its target, the Sox9-TESCO enhancer, had appreciable transcriptional activity in in vitro assays, correlating with sequence degradation compared to Mus musculus counterparts. However, M. minutoides SRY activated its cognate TESCO to a moderate degree, and can clearly engage the male pathway in M. minutoides in the wild, indicating that SRY and TESCO may have co-evolved in M. minutoides to retain function above a threshold level. We suggest that weakening of the SRY/TESCO nexus may have facilitated the rise and spread of a variant X* chromosome carrying female-inducing modifier gene(s).

  19. The effects of the pre-reversal ExB drift, the EIA asymmetry, and magnetic activity on the equatorial spread F during solar maximum

    Directory of Open Access Journals (Sweden)

    C.-C. Lee

    2005-03-01

    Full Text Available We use a digisonde at Jicamarca and a chain of GPS receivers on the west side of South America to investigate the effects of the pre-reversal enhancement (PRE in ExB drift, the asymmetry (Ia of equatorial ionization anomaly (EIA, and the magnetic activity (Kp on the generation of equatorial spread F (ESF. Results show that the ESF appears frequently in summer (November, December, January, and February and equinoctial (March, April, September, and October months, but rarely in winter (May, June, July, and August months. The seasonal variation in the ESF is associated with those in the PRE ExB drift and Ia. The larger ExB drift (>20m/s and smaller |Ia| (<0.3 in summer and equinoctial months provide a preferable condition to development the ESF. Conversely, the smaller ExB drift and larger |Ia| are responsible for the lower ESF occurrence in winter months. Regarding the effects of magnetic activity, the ESF occurrence decreases with increasing Kp in the equinoctial and winter months, but not in the summer months. Furthermore, the larger and smaller ExB drifts are presented under the quiet (Kp<3 and disturbed (Kp≥3 conditions, respectively. These results indicate that the suppression in ESF and the decrease in ExB drifts are mainly caused by the decrease in the eastward electric field.

  20. Chemical Activation of the Hypoxia-Inducible Factor Reversibly Reduces Tendon Stem Cell Proliferation, Inhibits Their Differentiation, and Maintains Cell Undifferentiation.

    Science.gov (United States)

    Menon, Alessandra; Creo, Pasquale; Piccoli, Marco; Bergante, Sonia; Conforti, Erika; Banfi, Giuseppe; Randelli, Pietro; Anastasia, Luigi

    2018-01-01

    Adult stem cell-based therapeutic approaches for tissue regeneration have been proposed for several years. However, adult stem cells are usually limited in number and difficult to be expanded in vitro, and they usually tend to quickly lose their potency with passages, as they differentiate and become senescent. Culturing stem cells under reduced oxygen tensions (below 21%) has been proposed as a tool to increase cell proliferation, but many studies reported opposite effects. In particular, cell response to hypoxia seems to be very stem cell type specific. Nonetheless, it is clear that a major role in this process is played by the hypoxia inducible factor (HIF), the master regulator of cell response to oxygen deprivation, which affects cell metabolism and differentiation. Herein, we report that a chemical activation of HIF in human tendon stem cells reduces their proliferation and inhibits their differentiation in a reversible and dose-dependent manner. These results support the notion that hypoxia, by activating HIF, plays a crucial role in preserving stem cells in an undifferentiated state in the "hypoxic niches" present in the tissue in which they reside before migrating in more oxygenated areas to heal a damaged tissue.

  1. Chemical Activation of the Hypoxia-Inducible Factor Reversibly Reduces Tendon Stem Cell Proliferation, Inhibits Their Differentiation, and Maintains Cell Undifferentiation

    Directory of Open Access Journals (Sweden)

    Alessandra Menon

    2018-01-01

    Full Text Available Adult stem cell-based therapeutic approaches for tissue regeneration have been proposed for several years. However, adult stem cells are usually limited in number and difficult to be expanded in vitro, and they usually tend to quickly lose their potency with passages, as they differentiate and become senescent. Culturing stem cells under reduced oxygen tensions (below 21% has been proposed as a tool to increase cell proliferation, but many studies reported opposite effects. In particular, cell response to hypoxia seems to be very stem cell type specific. Nonetheless, it is clear that a major role in this process is played by the hypoxia inducible factor (HIF, the master regulator of cell response to oxygen deprivation, which affects cell metabolism and differentiation. Herein, we report that a chemical activation of HIF in human tendon stem cells reduces their proliferation and inhibits their differentiation in a reversible and dose-dependent manner. These results support the notion that hypoxia, by activating HIF, plays a crucial role in preserving stem cells in an undifferentiated state in the “hypoxic niches” present in the tissue in which they reside before migrating in more oxygenated areas to heal a damaged tissue.

  2. Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone reverses the adverse effects of diet-induced obesity on oocyte quality.

    Science.gov (United States)

    Minge, Cadence E; Bennett, Brenton D; Norman, Robert J; Robker, Rebecca L

    2008-05-01

    Obesity and its physiological consequences are increasingly prevalent among women of reproductive age and are associated with infertility. To investigate, female mice were fed a high-fat diet until the onset of insulin resistance, followed by assessments of ovarian gene expression, ovulation, fertilization, and oocyte developmental competence. We report defects to ovarian function associated with diet-induced obesity (DIO) that result in poor oocyte quality, subsequently reduced blastocyst survival rates, and abnormal embryonic cellular differentiation. To identify critical cellular mediators of ovarian responses to obesity induced insulin resistance, DIO females were treated for 4 d before mating with an insulin-sensitizing pharmaceutical: glucose and lipid-lowering AMP kinase activator, 5-aminoimidazole 4-carboxamide-riboside, 30 mg/kg.d; sodium salicylate, IkappaK inhibitor that reverses insulin resistance, 50 mg/kg.d; or peroxisome proliferator activated receptor-gamma agonist rosiglitazone, 10 mg/kg.d. 5-aminoimidazole 4-carboxamide-riboside or sodium salicylate treatment did not have significant effects on the reproductive parameters examined. However, embryonic development to the blastocyst stage was significantly improved when DIO mice were treated with rosiglitazone, effectively repairing development rates. Rosiglitazone also normalized DIO-associated abnormal blastomere allocation to the inner cell mass. Such improvements to oocyte quality were coupled with weight loss, improved glucose metabolism, and changes in ovarian mRNA expression of peroxisome proliferator activated receptor-regulated genes, Cd36, Scarb1, and Fabp4 cholesterol transporters. These studies demonstrate that peri-conception treatment with select insulin-sensitizing pharmaceuticals can directly influence ovarian functions and ultimately exert positive effects on oocyte developmental competence. Improved blastocyst quality in obese females treated with rosiglitazone before mating

  3. Reversible conformational change in herpes simplex virus glycoprotein B with fusion-from-without activity is triggered by mildly acidic pH

    Directory of Open Access Journals (Sweden)

    Nicola Anthony V

    2010-12-01

    Full Text Available Abstract Background The pre-fusion form of the herpes simplex virus (HSV fusion protein gB undergoes pH-triggered conformational change in vitro and during viral entry (Dollery et al., J. Virol. 84:3759-3766, 2010. The antigenic structure of gB from the fusion-from-without (FFWO strain of HSV-1, ANG path, resembles wild type gB that has undergone pH-triggered changes. Together, changes in the antigenic and oligomeric conformation of gB correlate with fusion activity. We tested whether the pre-fusion form of FFWO gB undergoes altered conformational change in response to low pH. Results A pH of 5.5 - 6.0 altered the conformation of Domains I and V of FFWO gB, which together comprise the functional region containing the hydrophobic fusion loops. The ANG path gB oligomer was altered at a similar pH. All changes were reversible. In wild type HSV lacking the UL45 protein, which has been implicated in gB-mediated fusion, gB still underwent pH-triggered changes. ANG path entry was inactivated by pretreatment of virions with low pH. Conclusion The pre-fusion conformation of gB with enhanced fusion activity undergoes alteration in antigenic structure and oligomeric conformation in response to acidic pH. We propose that endosomal pH triggers conformational change in mutant gB with FFWO activity in a manner similar to wild type. Differences apart from this trigger may account for the increased fusion activity of FFWO gB.

  4. Extract of Bauhinia vahlii Shows Antihyperglycemic Activity, Reverses Oxidative Stress, and Protects against Liver Damage in Streptozotocin-induced Diabetic Rats

    Science.gov (United States)

    Elbanna, Ahmed H.; Nooh, Mohammed M.; Mahrous, Engy A.; Khaleel, Amal E.; Elalfy, Taha S.

    2017-01-01

    Background: Several studies have affirmed the effectiveness of some Bauhinia plants as antihyperglycemic agents. Objective: We investigated the possible effect of Bauhinia vahlii leaves extract in reducing hyperglycemia and reversing signs of organ damage associated with diabetes in streptozotocin (STZ) rat model. Materials and Methods: Both polar fraction of the B. vahlii leaves (defatted ethanolic extract [DEE]) and nonpolar fraction (n-hexane extract) were evaluated in vitro for α-glucosidase inhibition and 2,2-diphenyl-1-picrylhydrazyl radical scavenging potential. DEE was selected for further in vivo studies and was administered at two doses, i.e., 150 or 300 mg/kg to STZ-diabetic rats for 4 weeks. Results: Only DEE exhibited in vitro antioxidant and antihyperglycemic activities and its oral administration at both dose levels resulted in significant reduction in fasting blood glucose and glycated hemoglobin. Furthermore, signs of oxidative stress as indicated by hepatic reduced glutathione, nitric oxide, and malondialdehyde levels were completely reversed. In addition, histopathological examination and measurement of serum aspartate transaminase and alanine transaminase levels showed that DEE protected the liver from signs of liver pathogenesis when compared to diabetic untreated animals and those treated with metformin. Phytochemical analysis of DEE showed high flavonoids content with quercitrin as the major constituent along with other quercetin glycosides. Conclusion: This study strongly highlights the possible beneficial effect of B. vahlii leaves extract in relieving hyperglycemia and liver damage in STZ-diabetic rats and recommends further investigation of the value of quercetin derivatives in controlling diabetes and ameliorating liver damage associated with it. SUMMARY The polar fraction of the Bauhinia vahlii leaves (defatted ethanolic extract [DEE]) exhibited both in vitro antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl scavenging assay and

  5. Managing Reverse Logistics or Reversing Logistics Management?

    NARCIS (Netherlands)

    M.P. de Brito (Marisa)

    2004-01-01

    textabstractIn the past, supply chains were busy fine-tuning the logistics from raw material to the end customer. Today an increasing flow of products is going back in the chain. Thus, companies have to manage reverse logistics as well.This thesis contributes to a better understanding of reverse

  6. Reversible Thermoset Adhesives

    Science.gov (United States)

    Mac Murray, Benjamin C. (Inventor); Tong, Tat H. (Inventor); Hreha, Richard D. (Inventor)

    2016-01-01

    Embodiments of a reversible thermoset adhesive formed by incorporating thermally-reversible cross-linking units and a method for making the reversible thermoset adhesive are provided. One approach to formulating reversible thermoset adhesives includes incorporating dienes, such as furans, and dienophiles, such as maleimides, into a polymer network as reversible covalent cross-links using Diels Alder cross-link formation between the diene and dienophile. The chemical components may be selected based on their compatibility with adhesive chemistry as well as their ability to undergo controlled, reversible cross-linking chemistry.

  7. Optimization and validation of a reversed-phase high performance liquid chromatography method for the measurement of bovine liver methylmalonyl-coenzyme a mutase activity.

    Science.gov (United States)

    Ouattara, Bazoumana; Duplessis, Mélissa; Girard, Christiane L

    2013-10-16

    Methylmalonyl-CoA mutase (MCM) is an adenosylcobalamin-dependent enzyme that catalyses the interconversion of (2R)-methylmalonyl-CoA to succinyl-CoA. In humans, a deficit in activity of MCM, due to an impairment of intracellular formation of adenosylcobalamin and methylcobalamin results in a wide spectrum of clinical manifestations ranging from moderate to fatal. Consequently, MCM is the subject of abundant literature. However, there is a lack of consensus on the reliable method to monitor its activity. This metabolic pathway is highly solicited in ruminants because it is essential for the utilization of propionate formed during ruminal fermentation. In lactating dairy cows, propionate is the major substrate for glucose formation. In present study, a reversed-phase high performance liquid chromatography (RP-HPLC) was optimized and validated to evaluate MCM activity in bovine liver. The major aim of the study was to describe the conditions to optimize reproducibility of the method and to determine stability of the enzyme and its product during storage and processing of samples. Specificity of the method was good, as there was no interfering peak from liver extract at the retention times corresponding to methylmalonyl-CoA or succinyl-CoA. Repeatability of the method was improved as compared to previous RP-HPLC published data. Using 66 μg of protein, intra-assay coefficient of variation (CV) of specific activities, ranged from 0.90 to 8.05% and the CV inter-day was 7.40%. Storage and processing conditions (frozen homogenate of fresh tissue vs. fresh homogenate of tissue snapped in liquid nitrogen) did not alter the enzyme activity. The analyte was also stable in liver crude extract for three frozen/thawed cycles when stored at -20°C and thawed to room temperature. The improved method provides a way for studying the effects of stages of lactation, diet composition, and physiology in cattle on MCM activity over long periods of time, such as a complete lactation period

  8. Structural Basis for the Inhibition of RNase H Activity of HIV-1 Reverse Transcriptase by RNase H Active Site-Directed Inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Su, Hua-Poo; Yan, Youwei; Prasad, G. Sridhar; Smith, Robert F.; Daniels, Christopher L.; Abeywickrema, Pravien D.; Reid, John C.; Loughran, H. Marie; Kornienko, Maria; Sharma, Sujata; Grobler, Jay A.; Xu, Bei; Sardana, Vinod; Allison, Timothy J.; Williams, Peter D.; Darke, Paul L.; Hazuda, Daria J.; Munshi, Sanjeev (Merck)

    2010-09-02

    HIV/AIDS continues to be a menace to public health. Several drugs currently on the market have successfully improved the ability to manage the viral burden in infected patients. However, new drugs are needed to combat the rapid emergence of mutated forms of the virus that are resistant to existing therapies. Currently, approved drugs target three of the four major enzyme activities encoded by the virus that are critical to the HIV life cycle. Although a number of inhibitors of HIV RNase H activity have been reported, few inhibit by directly engaging the RNase H active site. Here, we describe structures of naphthyridinone-containing inhibitors bound to the RNase H active site. This class of compounds binds to the active site via two metal ions that are coordinated by catalytic site residues, D443, E478, D498, and D549. The directionality of the naphthyridinone pharmacophore is restricted by the ordering of D549 and H539 in the RNase H domain. In addition, one of the naphthyridinone-based compounds was found to bind at a second site close to the polymerase active site and non-nucleoside/nucleotide inhibitor sites in a metal-independent manner. Further characterization, using fluorescence-based thermal denaturation and a crystal structure of the isolated RNase H domain reveals that this compound can also bind the RNase H site and retains the metal-dependent binding mode of this class of molecules. These structures provide a means for structurally guided design of novel RNase H inhibitors.

  9. Reversible Second Order Kinetics of Sorption-Desorption of Cr(VI Ion on Activated Carbon from Palm Empty Fruit Bunches

    Directory of Open Access Journals (Sweden)

    Iip Izul Falah

    2015-11-01

    Full Text Available Activated carbon (AC from palm empty fruit bunches has been prepared, and this material was then used to adsorb Cr(VI from a solution. Characterization of the AC was conducted by detection of its functional groups, determination of total volatile compounds (VC content and its iodine number. Study on sorption-desorption kinetics was conducted by comparing results of evaluations of several models with proposed reversible second order model using the data produced in this work. Results of the works showed that the AC had similar characters compared with the AC produced by previous researchers. Application of the kinetics models on sorption Cr(VI onto the AC showed that nearly all of the models gave a good linearity. However, only the proposed model had a good relation with Langmuir isotherm, with respectively sorption (ks and desorption (kd constants were 5.75 x 10-4 L.mg‑1.min-1 and 2.20 x 10-3 min-1; maximum sorption capacity, qm = 20.00 mg.g-1; and equilibrium constant, K from kinetics experiment (0.261 L.mg-1 was comparable with the result from the isotherm experiment (0.269 L.mg-1. Hence, using this model, kinetics and Langmuir parameters can probably be determined from a single kinetics data experiment.

  10. Mechanism of Activating the Proprioceptive NT-3/TrkC Signalling Pathway by Reverse Intervention for the Anterior Cruciate Ligament–Hamstring Reflex Arc with Electroacupuncture

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    2018-01-01

    Full Text Available The anterior cruciate ligament (ACL is an important structure maintaining stability of the knee joints. Deficits in physical stability and the proprioceptive capabilities of the knee joints are observed, when the ACL is damaged. Additionally, a unilateral ACL injury can affect bilateral knee proprioception; therefore, proprioception of the ACL may play a key role in stability. Electroacupuncture therapy has a definite effect nerve regeneration. In this study, cynomolgus monkeys were randomly divided into 4 groups: the model control group, intervention of the injured knee with electroacupuncture (IIKE group, intervention of the bilateral knees with electroacupuncture (IBKE group, and the blank control group. The unilateral ACL injury model was developed in IIKE and IBKE groups; acupuncture points around the knees underwent intervention similarly in the IIKE and IBKE groups. Then, mRNA and protein expressions of NT-3 and TrkC in the dorsal root ganglion and of growth-associated protein-43 in the ACL increased according to reverse-transcription quantitative polymerase chain reaction and Western blotting results. Decreased incubations and increased amplitudes were found for somatosensory-evoked potentials and motor nerve conduction velocity. The finding indicates that electroacupuncture may play an important role in the recovery of proprioception in the ACL by activating the NT-3/TrkC signalling pathway.

  11. Experimental and theoretical studies of active control of resistive wall mode growth in the EXTRAP T2R reversed-field pinch

    International Nuclear Information System (INIS)

    Drake, J.R.; Brunsell, P.R.; Yadikin, D.; Cecconello, M.; Malmberg, J.A.; Gregoratto, D.; Paccagnella, R.; Bolzonella, T.; Manduchi, G.; Marrelli, L.; Ortolani, S.; Spizzo, G.; Zanca, P.; Bondeson, A.; Liu, Y.Q.

    2005-01-01

    Active feedback control of resistive wall modes (RWMs) has been demonstrated on the EXTRAP T2R reversed-field pinch experiment. The control system includes a sensor consisting of an array of magnetic coils (measuring mode harmonics) and an actuator consisting of a saddle coil array (producing control harmonics). Closed-loop (feedback) experiments using a digital controller based on a real time Fourier transform of sensor data have been studied for cases where the feedback gain was constant and real for all harmonics (intelligent-shell) and cases where the feedback gain could be set for selected harmonics, with both real or complex values (targeted-harmonics). The growth of the dominant RWMs can be suppressed by feedback for both the intelligent-shell and targeted-harmonic control systems. Because the number of toroidal positions of saddle coils in the array is half the number of sensors, it is predicted and observed experimentally that the control harmonic spectrum has sidebands. As a result, each control harmonic has to control simultaneously two mode harmonics. Real gains can stabilize non-rotating RWMs, while complex gains give better results for (slowly) rotating RWMs. In addition open loop experiments have been used to observe the effects of resonant field errors applied to unstable, marginally stable and robustly stable modes. The observed effects of field errors are consistent with the thin-wall model, where mode growth is proportional to the resonant field error amplitude and the wall penetration time for that mode harmonic. (author)

  12. Doxorubicin-loaded micelles of reverse poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) block copolymers as efficient "active" chemotherapeutic agents.

    Science.gov (United States)

    Cambón, A; Rey-Rico, A; Mistry, D; Brea, J; Loza, M I; Attwood, D; Barbosa, S; Alvarez-Lorenzo, C; Concheiro, A; Taboada, P; Mosquera, V

    2013-03-10

    Five reverse poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) block copolymers, BOnEOmBOn, with BO ranging from 8 to 21 units and EO from 90 to 411 were synthesized and evaluated as efficient chemotherapeutic drug delivery nanocarriers and inhibitors of the P-glycoprotein (P-gp) efflux pump in a multidrug resistant (MDR) cell line. The copolymers were obtained by reverse polymerization of poly(butylene oxide), which avoids transfer reaction and widening of the EO block distribution, commonly found in commercial poly(ethylene oxide)-poly(propylene oxide) block copolymers (poloxamers). BOnEOmBOn copolymers formed spherical micelles of 10-40 nm diameter at lower concentrations (one order of magnitude) than those of equivalent poloxamers. The influence of copolymer block lengths and BO/EO ratios on the solubilization capacity and protective environment for doxorubicin (DOXO) was investigated. Micelles showed drug loading capacity ranging from ca. 0.04% to 1.5%, more than 150 times the aqueous solubility of DOXO, and protected the cargo from hydrolysis for more than a month due to their greater colloidal stability in solution. Drug release profiles at various pHs, and the cytocompatibility and cytotoxicity of the DOXO-loaded micelles were assessed in vitro. DOXO loaded in the polymeric micelles accumulated more slowly inside the cells than free DOXO due to its sustained release. All copolymers were found to be cytocompatible, with viability extents larger than 95%. In addition, the cytotoxicity of DOXO-loaded micelles was higher than that observed for free drug solutions in a MDR ovarian NCI-ADR-RES cell line which overexpressed P-gp. The inhibition of the P-gp efflux pump by some BOnEOmBOn copolymers, similar to that measured for the common P-gp inhibitor verapamil, favored the retention of DOXO inside the cell increasing its cytotoxic activity. Therefore, poly(butylene oxide)-poly(ethylene oxide) block copolymers offer interesting features as cell

  13. Tubal Ligation Reversal

    Science.gov (United States)

    ... seal off the fallopian tubes, such as the Essure or Adiana systems, generally aren't reversible. Why ... electrocautery). Some types of sterilization, such as the Essure or Adiana systems, aren't considered reversible. Risks ...

  14. Quality control of radiolabeled antibodies through simultaneous determination of antibody concentration and specific activity using time-resolved interaction analysis and reverse kinetic fit

    International Nuclear Information System (INIS)

    Andersson, K.; Mihaylova, D.; Wang, E.; Abrahamsen, L.; Buijs, J.; Bjoerkelund, H.

    2015-01-01

    Full text of publication follows. With the advent of efficient methods for producing proteins that bind to a defined target, the number of radiolabeled proteins, and in particular antibodies, used for medical imaging and cancer therapy is increasing rapidly. In line with this increase, focus should be put on methods for the quality control (QC). Proper antibody quality is of fundamental importance to guarantee safety and consistent efficacy for the patient. Adequate QC procedures exist for small radiolabeled synthetic compounds like FDG, but antibody based radiopharmaceuticals are different. Proteins are much more complex and fragile than the synthetic compounds, and hence require new methods for adequate characterization and QC. Yet another complication is the labeling where there is a risk that a subpopulation of the protein is damaged to the level that it no longer binds the target. Therefore, a new toolbox is required to fulfill the quality characterization of radiolabeled antibodies. We have developed a QC assay for the simultaneous determination of antibody function, concentration and specific activity. The assay is based on time-resolved detection of the antibody interaction with antigen-coated magnetic beads in LigandTracer instruments. The resulting binding curve is evaluated using reverse kinetic fits, where the known interaction parameters of the antibody-antigen interaction are set constant while as the concentration and signal level are fitted. The assay takes approximately 2 hours and the majority of the time constitutes automated data collection in the instrument. The QC assay has been tested on multiple antibody-antigen interactions and consistently provides repeatable results for concentration and specific activity, both with coefficient of variation (CV) less than 15%. We believe that this QC assay can improve the quality of radiolabeled therapeutic antibodies. (authors)

  15. Agmatine Reverses Sub-chronic Stress induced Nod-like Receptor Protein 3 (NLRP3) Activation and Cytokine Response in Rats.

    Science.gov (United States)

    Sahin, Ceren; Albayrak, Ozgur; Akdeniz, Tuğba F; Akbulut, Zeynep; Yanikkaya Demirel, Gulderen; Aricioglu, Feyza

    2016-10-01

    The activation of Nod-like receptor protein 3 (NLRP3) has lately been implicated in stress and depression as an initiator mechanism required for the production of interleukin (IL)-1β and IL-18. Agmatine, an endogenous polyamine widely distributed in mammalian brain, is a novel neurotransmitter/neuromodulator, with antistress, anxiolytic and antidepressant-like effects. In this study, we examined the effect of exogenously administered agmatine on NLRP3 inflammasome pathway/cytokine responses in rats exposed to restraint stress for 7 days. The rats were divided into three groups: stress, stress+agmatine (40 mg/kg; i.p.) and control groups. Agmatine significantly down-regulated the gene expressions of all stress-induced NLRP3 inflammasome components (NLRP3, NF-κB, PYCARD, caspase-1, IL-1β and IL-18) in the hippocampus and prefrontal cortex (PFC) and reduced pro-inflammatory cytokine levels not only in both brain regions, but also in serum. Stress-reduced levels of IL-4 and IL-10, two major anti-inflammatory cytokines, were restored back to normal by agmatine treatment in the PFC. The findings of the present study suggest that stress-activated NLRP3 inflammasome and cytokine responses are reversed by an acute administration of agmatine. Whether antidepressant-like effect of agmatine can somehow, at least partially, be mediated by the inhibition of NLRP3 inflammasome cascade and relevant inflammatory responses requires further studies in animal models of depression. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  16. The effects of the pre-reversal ExB drift, the EIA asymmetry, and magnetic activity on the equatorial spread F during solar maximum

    Directory of Open Access Journals (Sweden)

    C.-C. Lee

    2005-03-01

    Full Text Available We use a digisonde at Jicamarca and a chain of GPS receivers on the west side of South America to investigate the effects of the pre-reversal enhancement (PRE in ExB drift, the asymmetry (Ia of equatorial ionization anomaly (EIA, and the magnetic activity (Kp on the generation of equatorial spread F (ESF. Results show that the ESF appears frequently in summer (November, December, January, and February and equinoctial (March, April, September, and October months, but rarely in winter (May, June, July, and August months. The seasonal variation in the ESF is associated with those in the PRE ExB drift and Ia. The larger ExB drift (>20m/s and smaller |Ia| (<0.3 in summer and equinoctial months provide a preferable condition to development the ESF. Conversely, the smaller ExB drift and larger |Ia| are responsible for the lower ESF occurrence in winter months. Regarding the effects of magnetic activity, the ESF occurrence decreases with increasing Kp in the equinoctial and winter months, but not in the summer months. Furthermore, the larger and smaller ExB drifts are presented under the quiet (Kp<3 and disturbed (Kp≥3 conditions, respectively. These results indicate that the suppression in ESF and the decrease in ExB drifts are mainly caused by the decrease in the eastward electric field.

  17. Reverse logistics - a framework

    NARCIS (Netherlands)

    M.P. de Brito (Marisa); R. Dekker (Rommert)

    2002-01-01

    textabstractIn this paper we define and compare Reverse Logistics definitions. We start by giving an understanding framework of Reverse Logistics: the why-what-how. By this means, we put in context the driving forces for Reverse Logistics, a typology of return reasons, a classification of

  18. A Framework for Reverse Logistics

    NARCIS (Netherlands)

    M.P. de Brito (Marisa); R. Dekker (Rommert)

    2003-01-01

    textabstractReverse Logistics has been stretching out worldwide, involving all the layers of supply chains in various industry sectors. While some actors in the chain have been forced to take products back, others have pro-actively done so, attracted by the value in used products One way or the

  19. Reverse Zymography: Overview and Pitfalls.

    Science.gov (United States)

    Sharma, Kanika; Bhattacharyya, Debasish

    2017-01-01

    Reverse zymography is a technique by which protease inhibitor(s) in a sample could be electrophoretically separated in a substrate-impregnated acrylamide gel and their relative abundance could be semi-quantified. The gel after electrophoresis is incubated with a protease when the impregnated substrate and all other proteins of the sample are degraded into small peptides except the inhibitor(s) that show clear bands against a white background. Since reverse zymography cannot distinguish between a protease inhibitor and a protein that is resistant against proteolysis, the results should be confirmed from inhibition of protease activity by solution state assay.

  20. Reverse osmosis application studies

    International Nuclear Information System (INIS)

    Golomb, A.

    1982-02-01

    To assess the feasibility of applying reverse osmosis (RO) and ultrafiltration (UF) for effective treatment of process and waste streams from operations at Ontario Hydro's thermal and nuclear stations, an extensive literature survey has been carried out. It is concluded that RO is not at present economic for pretreatment of Great Lakes water prior to ion exchange demineralization for boiler makeup. Using both conventional and novel commercial membrane modules, RO pilot studies are recommended for treatment of boiler cleaning wastes, fly ash leachates, and flue gas desulphurization scrubber discharges for removal of heavy metals. Volume reduction and decontamination of nuclear station low-level active liquid waste streams by RO/UF also appear promising. Research programmes are proposed

  1. Experimental and theoretical studies of active control of resistive wall mode growth in the EXTRAP T2R reversed-field pinch

    Science.gov (United States)

    Drake, J. R.; Brunsell, P. R.; Yadikin, D.; Cecconello, M.; Malmberg, J. A.; Gregoratto, D.; Paccagnella, R.; Bolzonella, T.; Manduchi, G.; Marrelli, L.; Ortolani, S.; Spizzo, G.; Zanca, P.; Bondeson, A.; Liu, Y. Q.

    2005-07-01

    Active feedback control of resistive wall modes (RWMs) has been demonstrated in the EXTRAP T2R reversed-field pinch experiment. The control system includes a sensor consisting of an array of magnetic coils (measuring mode harmonics) and an actuator consisting of a saddle coil array (producing control harmonics). Closed-loop (feedback) experiments using a digital controller based on a real time Fourier transform of sensor data have been studied for cases where the feedback gain was constant and real for all harmonics (corresponding to an intelligent-shell) and cases where the feedback gain could be set for selected harmonics, with both real and complex values (targeted harmonics). The growth of the dominant RWMs can be reduced by feedback for both the intelligent-shell and targeted-harmonic control systems. Because the number of toroidal positions of the saddle coils in the array is half the number of the sensors, it is predicted and observed experimentally that the control harmonic spectrum has sidebands. Individual unstable harmonics can be controlled with real gains. However if there are two unstable mode harmonics coupled by the sideband effect, control is much less effective with real gains. According to the theory, complex gains give better results for (slowly) rotating RWMs, and experiments support this prediction. In addition, open loop experiments have been used to observe the effects of resonant field errors applied to unstable, marginally stable and robustly stable modes. The observed effects of field errors are consistent with the thin-wall model, where mode growth is proportional to the resonant field error amplitude and the wall penetration time for that mode harmonic.

  2. Experimental and theoretical studies of active control of resistive wall mode growth in the EXTRAP T2R reversed-field pinch

    International Nuclear Information System (INIS)

    Drake, J.R.; Brunsell, P.R.; Yadikin, D.

    2005-01-01

    Active feedback control of resistive wall modes (RWMs) has been demonstrated in the EXTRAP T2R reversed-field pinch experiment. The control system includes a sensor consisting of an array of magnetic coils (measuring mode harmonics) and an actuator consisting of a saddle coil array (producing control harmonics). Closed-loop (feedback) experiments using a digital controller based on a real time Fourier transform of sensor data have been studied for cases where the feedback gain was constant and real for all harmonics (corresponding to an intelligent-shell) and cases where the feedback gain could be set for selected harmonics, with both real and complex values (targeted harmonics). The growth of the dominant RWMs can be reduced by feedback for both the intelligent-shell and targeted-harmonic control systems. Because the number of toroidal positions of the saddle coils in the array is half the number of the sensors, it is predicted and observed experimentally that the control harmonic spectrum has sidebands. Individual unstable harmonics can be controlled with real gains. However if there are two unstable mode harmonics coupled by the sideband effect, control is much less effective with real gains. According to the theory, complex gains give better results for (slowly) rotating RWMs, and experiments support this prediction. In addition, open loop experiments have been used to observe the effects of resonant field errors applied to unstable, marginally stable and robustly stable modes. The observed effects of field errors are consistent with the thin-wall model, where mode growth is proportional to the resonant field error amplitude and the wall penetration time for that mode harmonic

  3. Study of the influence of surfactants on the activity coefficients and mass transfer coefficients of methanol in aqueous mixtures by reversed-flow gas chromatography.

    Science.gov (United States)

    Kotsalos, Efthimios; Brezovska, Boryana; Sevastos, Dimitrios; Vagena, Artemis; Koliadima, Athanasia; Kapolos, John; Karaiskakis, George

    2017-11-17

    This work focuses on the influences of surfactants on the activity coefficients, γ, of methanol in binary mixtures with water, as well as on the mass transfer coefficients, k c , for the evaporation of methanol, which is a ubiquitous component in the troposphere, from mixtures of methanol with water at various surfactant's and methanol's concentrations. The technique used is the Reversed-Flow Gas Chromatography (R.F.G.C.), a version of Inverse Gas Chromatography, which allows determining both parameters by performing only one experiment for the k c parameter and two experiments for the γ parameter. The k c and γ values decrease in the presence of the three surfactants used (CTAB, SDS, TRITON X-100) at all methanol's and surfactant's concentrations. The decrease in the methanol's molar fraction, at constant number of surfactant films leads to a decrease in the k c and γ values, while the decrease in the surfactant's concentration, at constant methanol's molar fraction leads to an increase in both the k c and γ parameters. Mass transfer coefficients for the evaporation of methanol at the surfactant films, are also calculated which are approximately between 4 and 5 orders of magnitude larger than the corresponding mass transfer coefficients at the liquid films. Finally, thicknesses of the boundary layer of methanol in the mixtures of methanol with water were determined. The quantities found are compared with those given in the literature or calculated theoretically using various empirical equations. The precision of the R.F.G.C. method for measuring γ and k c parameters is approximately high (94.3-98.0%), showing that R.F.G.C. can be used with success not only for the thermodynamic study of solutions, but also for the interphase transport. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. GLT1 overexpression reverses established neuropathic pain-related behavior and attenuates chronic dorsal horn neuron activation following cervical spinal cord injury.

    Science.gov (United States)

    Falnikar, Aditi; Hala, Tamara J; Poulsen, David J; Lepore, Angelo C

    2016-03-01

    Development of neuropathic pain occurs in a major portion of traumatic spinal cord injury (SCI) patients, resulting in debilitating and often long-term physical and psychological burdens. Following SCI, chronic dysregulation of extracellular glutamate homeostasis has been shown to play a key role in persistent central hyperexcitability of superficial dorsal horn neurons that mediate pain neurotransmission, leading to various forms of neuropathic pain. Astrocytes express the major CNS glutamate transporter, GLT1, which is responsible for the vast majority of functional glutamate uptake, particularly in the spinal cord. In our unilateral cervical contusion model of mouse SCI that is associated with ipsilateral forepaw heat hypersensitivity (a form of chronic at-level neuropathic pain-related behavior), we previously reported significant and long-lasting reductions in GLT1 expression and functional GLT1-mediated glutamate uptake in cervical spinal cord dorsal horn. To therapeutically address GLT1 dysfunction following cervical contusion SCI, we injected an adeno-associated virus type 8 (AAV8)-Gfa2 vector into the superficial dorsal horn to increase GLT1 expression selectively in astrocytes. Compared to both contusion-only animals and injured mice that received AAV8-eGFP control injection, AAV8-GLT1 delivery increased GLT1 protein expression in astrocytes of the injured cervical spinal cord dorsal horn, resulting in a significant and persistent reversal of already-established heat hypersensitivity. Furthermore, AAV8-GLT1 injection significantly reduced expression of the transcription factor and marker of persistently increased neuronal activation, ΔFosB, in superficial dorsal horn neurons. These results demonstrate that focal restoration of GLT1 expression in the superficial dorsal horn is a promising target for treating chronic neuropathic pain following SCI. © 2015 Wiley Periodicals, Inc.

  5. Thorium and uranium redox-active ligand complexes; reversible intramolecular electron transfer in U(dpp-BIAN)2/ U(dpp-BIAN)2(THE)

    Energy Technology Data Exchange (ETDEWEB)

    Schelter, Eric John [Los Alamos National Laboratory; Wu, Ruilian [Los Alamos National Laboratory; Scott, Brian L [Los Alamos National Laboratory; Thompson, Joe D [Los Alamos National Laboratory; Batista, Enrique R [Los Alamos National Laboratory; Morris, David E [Los Alamos National Laboratory; Kiplinger, Jaqueline L [Los Alamos National Laboratory

    2008-01-01

    Actinide complexes of the redox-active ligand dpp-BIAN{sup 2-} (dpp-BIAN = bis(2,6-diisopropylphenyl)acenaphthylene), An(dpp-BIAN){sub 2}(THF){sub n} (An = Th, n = 1; An = U, n = 0, 1) have been prepared. Solid-state magnetic and single-crystal X-ray data for U(dpp-BIAN){sub 2}(THF){sub n} show when n = 0, the complex exists in an f{sup 2}-{pi}*{sup 4} configuration; whereas an intramolecular electron transfer occurs for n = 1, resulting in an f{sup 3}-{pi}*{sup 3} ground configuration. The magnetic data also indicate that interconversion between the two forms of the complex is possible, limited only by the ability of THF vapor to penetrate the solid on cooling of the sample. Spectroscopic data indicate the complex exists solely in the f{sup 2}-{pi}*{sup 4} form in solution, evidenced by the appearance of only small changes in the electronic absorption spectra of the U(dpp-BIAN){sub 2} complex on titration with THF and by measurement of the solution magnetic moment m d{sub 8}-tetrahydrofuran using Evans method. Electrochemistry of the complexes is reported, with small differences observed in wave potentials between metals and in the presence of THF. These data represent the first example of a well-defined, reversible intramolecular electron transfer in an f-element complex and the second example of oxidation state change through dative interaction with a metal ion.

  6. Early initiation of highly active antiretroviral therapy fails to reverse immunovirological abnormalities in gut-associated lymphoid tissue induced by acute HIV infection.

    Science.gov (United States)

    Tincati, Camilla; Biasin, Mara; Bandera, Alessandra; Violin, Michela; Marchetti, Giulia; Piacentini, Luca; Vago, Gian Luca; Balotta, Claudia; Moroni, Mauro; Franzetti, Fabio; Clerici, Mario; Gori, Andrea

    2009-01-01

    During the acute phase of HIV infection, large CD4+ T-cell depletion occurs in the gastrointestinal tract. The kinetics of CD4+ T-cell decrease and highly active antiretroviral therapy (HAART)-mediated immune reconstitution were evaluated. Rectosigmoid colonic (RSC) biopsies and blood samples of nine patients with acute HIV infection were collected. CD4+ T-cell count, HIV RNA, intracellular HIV DNA and messenger RNA cytokine expression were evaluated before and after 6 months of HAART. All nine patients presented symptomatic retroviral infection. Early HAART was associated with a sustained and comparable reduction of HIV RNA in plasma, peripheral blood mononuclear cells (PBMCs) and RSC biopsies. HIV DNA decreased in PBMCs, but was only marginally reduced in RSC biopsies. Comparisons between reduction rates of HIV DNA in these two compartments confirmed that HIV DNA clearance was less efficient in RSC biopsies compared with PBMCs. Assessment of immunological profiles in PBMCs and RSC biopsies showed that the T-helper (Th)1-like/Th2-like ratio was sharply decreased in RSC biopsies and increased in PBMCs throughout the study period. A persistent Th2-like profile was detected in RSC biopsies. Efficient clearing of HIV DNA observed in PBMCs correlated with the establishment of a more favourable Th1-like profile. A less efficient clearance of intracellular HIV DNA following early introduction of HAART is associated with persistent immunological impairment in gut-associated lymphoid tissue (GALT), which is reflected by the skewed expression of cytokines in this reservoir. The present study shows that early initiation of HAART, in the short-term, is not effective in containing the establishment of HIV infection and in reversing associated immunological GALT abnormalities.

  7. Reversible flowchart languages and the structured reversible program theorem

    DEFF Research Database (Denmark)

    Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

    2008-01-01

    Many irreversible computation models have reversible counterparts, but these are poorly understood at present. We introduce reversible flowcharts with an assertion operator and show that any reversible flowchart can be simulated by a structured reversible flowchart using only three control flow...... operators. Reversible flowcharts are r- Turing-complete, meaning that they can simuluate reversible Turing machines without garbage data. We also demonstrate the injectivization of classical flowcharts into reversible flowcharts. The reversible flowchart computation model provides a theoretical...

  8. Reverse logistics: A review of case studies

    NARCIS (Netherlands)

    Brito, de M.P.; Dekker, Rommert; Flapper, S.D.P.; Fleischmann, B.; Klose, A.

    2004-01-01

    This paper gives an overview of scientific literature that describes and discusses cases of reverse logistics activities in practice. Over sixty case studies are considered. Based on these studies we are able to indicate critical factors for the practice of reverse logistics. In addition we compare

  9. Introduction to reversible computing

    CERN Document Server

    Perumalla, Kalyan S

    2013-01-01

    Few books comprehensively cover the software and programming aspects of reversible computing. Filling this gap, Introduction to Reversible Computing offers an expanded view of the field that includes the traditional energy-motivated hardware viewpoint as well as the emerging application-motivated software approach. Collecting scattered knowledge into one coherent account, the book provides a compendium of both classical and recently developed results on reversible computing. It explores up-and-coming theories, techniques, and tools for the application of rever

  10. Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation through activating the NR2B subunits of NMDA receptors

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Wen-Zhu [Anesthesia and Operation Center, Hainan Branch of Chinese PLA General Hospital, Hainan 572013 (China); Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853 (China); Miao, Yu-Liang [Department of Anesthesiology, PLA No. 306 Hospital, Beijing 100101 (China); Guo, Wen-Zhi [Department of Anesthesiology, Beijing Military General Hospital of Chinese People’s Liberation Army, Beijing 100700 (China); Wu, Wei, E-mail: wwzwgk@163.com [Department of Head and Neck Surgery of Otolaryngology, PLA No. 306 Hospital, Beijing 100101 (China); Li, Bao-Wei [Department of Head and Neck Surgery of Otolaryngology, PLA No. 306 Hospital, Beijing 100101 (China); An, Li-Na [Department of Anesthesiology, Armed Police General Hospital, Beijing 100039 (China); Fang, Wei-Wu [Department of Anesthesiology, PLA No. 306 Hospital, Beijing 100101 (China); Mi, Wei-Dong, E-mail: elite2005gg@163.com [Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853 (China)

    2014-04-25

    Highlights: • Leptin promotes the proliferation of neural stem cells isolated from embryonic mouse hippocampus. • Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation. • The effects of leptin are partially mediated by upregulating NR2B subunits. - Abstract: Corticosterone inhibits the proliferation of hippocampal neural stem cells (NSCs). The removal of corticosterone-induced inhibition of NSCs proliferation has been reported to contribute to neural regeneration. Leptin has been shown to regulate brain development, improve angiogenesis, and promote neural regeneration; however, its effects on corticosterone-induced inhibition of NSCs proliferation remain unclear. Here we reported that leptin significantly promoted the proliferation of hippocampal NSCs in a concentration-dependent pattern. Also, leptin efficiently reversed the inhibition of NSCs proliferation induced by corticosterone. Interestingly, pre-treatment with non-specific NMDA antagonist MK-801, specific NR2B antagonist Ro 25-6981, or small interfering RNA (siRNA) targeting NR2B, significantly blocked the effect of leptin on corticosterone-induced inhibition of NSCs proliferation. Furthermore, corticosterone significantly reduced the protein expression of NR2B, whereas pre-treatment with leptin greatly reversed the attenuation of NR2B expression caused by corticosterone in cultured hippocampal NSCs. Our findings demonstrate that leptin reverses the corticosterone-induced inhibition of NSCs proliferation. This process is, at least partially mediated by increased expression of NR2B subunits of NMDA receptors.

  11. Reversibility of female sterilization.

    Science.gov (United States)

    Siegler, A M; Hulka, J; Peretz, A

    1985-04-01

    The discussion considers the current status of reversibility of sterilization in the US and describes clinical and experimental efforts for developing techniques designed for reversibility. It focuses on regret following sterilization, reversal potential of current sterilization techniques, patient selection, current reversal techniques, results of sterilization procedures, experimental approaches to reversal of current techniques of sterilization, and sterilization procedures devised for reversibility, in humans and in animals. Request is the 1st stage of reversal, but a request for sterilization reversal (SR) does not always mean regret for a decision made at the time. Frequently it is a wish to restore fertility because life circumstances have changed after a sterilization that was ppropriate at the time it was performed. Schwyhart and Kutner reviewed 22 studies published between 1949-69 in which they found that the percentage of patients regretting the procedure ranged from 1.3-15%. Requests for reversal remain low in most countries, but if sterilization becomes a more popular method of contraception, requests will also increase. The ideal operation considered as a reversaible method of sterilization should include an easy, reliable outpatient method of tubal occlusion with miniml risk or patient discomfort that subsequently could be reversed without the need for a major surgical intervention. Endoscopic methods have progressed toward the 1st objective. A recent search of the literature uncovered few series of SR of more than 50 cases. The 767 operations found were analyzed with regard to pregnancy outcome. The precent of live births varied from 74-78.8%, and the occurance of tubal pregnancies ranged from 1.7-6.5%. All of the confounding variables in patient selection and small numbers of reported procedures preclude any conclusion about the different techniques or the number of operations that give a surgeon a level of expertise. Few authors classify their

  12. Building a Better Microreactor: Enzyme Catalysis in AOT/Bile Salt Reversed Micelles

    National Research Council Canada - National Science Library

    McGown, Linda

    2001-01-01

    .... We have shown that trihydroxy bile salts modify the interfacial properties of AOT reversed micelles, thereby affecting the reversed micellar structure, the biological activity of entrapped enzymes...

  13. Quantum reverse hypercontractivity

    Energy Technology Data Exchange (ETDEWEB)

    Cubitt, Toby [Department of Computer Science, University College London, London, United Kingdom and Centre for Quantum Information and Foundations, DAMTP, University of Cambridge, Cambridge (United Kingdom); Kastoryano, Michael [NBIA, Niels Bohr Institute, University of Copenhagen, 2100 Copenhagen (Denmark); Montanaro, Ashley [School of Mathematics, University of Bristol, Bristol (United Kingdom); Temme, Kristan [Institute for Quantum Information and Matter, California Institute of Technology, Pasadena, California 91125 (United States)

    2015-10-15

    We develop reverse versions of hypercontractive inequalities for quantum channels. By generalizing classical techniques, we prove a reverse hypercontractive inequality for tensor products of qubit depolarizing channels. We apply this to obtain a rapid mixing result for depolarizing noise applied to large subspaces and to prove bounds on a quantum generalization of non-interactive correlation distillation.

  14. Atrioventricular Pacemaker Lead Reversal

    Directory of Open Access Journals (Sweden)

    Mehmet K Aktas, MD

    2007-01-01

    Full Text Available During cardiac surgery temporary epicardial atrial and ventricular leads are placed in case cardiac pacing is required postoperatively. We present the first reported series of patients with reversal of atrioventricular electrodes in the temporary pacemaker without any consequent deleterious hemodynamic effect. We review the electrocardiographic findings and discuss the findings that lead to the discovery of atrioventricular lead reversal.

  15. An algebra of reversible computation.

    Science.gov (United States)

    Wang, Yong

    2016-01-01

    We design an axiomatization for reversible computation called reversible ACP (RACP). It has four extendible modules: basic reversible processes algebra, algebra of reversible communicating processes, recursion and abstraction. Just like process algebra ACP in classical computing, RACP can be treated as an axiomatization foundation for reversible computation.

  16. Sex reversal in vertebrates

    OpenAIRE

    2016-01-01

    This special topic issue of Sexual Development gives an overview of sex reversal in vertebrates, from fishes naturally changing their sex, to rodents escaping the mammalian SRY-determining system. It offers eight up-to-date reviews on specific subjects in sex reversal, considering fishes, amphibians, reptiles, birds, marsupials, and placental mammals, including humans. The broad scope of represented animals makes this ideal for students and researchers, especially those interested in the...

  17. Reverse chemomodulatory effects of the SIRT1 activators resveratrol and SRT1720 in Ewing's sarcoma cells: resveratrol suppresses and SRT1720 enhances etoposide- and vincristine-induced anticancer activity.

    Science.gov (United States)

    Sonnemann, Jürgen; Kahl, Melanie; Siranjeevi, Priyanka M; Blumrich, Annelie; Blümel, Lisa; Becker, Sabine; Wittig, Susan; Winkler, René; Krämer, Oliver H; Beck, James F

    2016-01-01

    SIRT1-activating compounds (STACs) may have potential in the management of cancer. However, the best-studied STAC, the naturally occurring compound resveratrol, is reported to have contradictory effects in combination chemotherapy regimens: It has been shown both to increase and to decrease the action of anticancer agents. To shed more light on this issue, we comparatively investigated the impact of resveratrol and the synthetic STAC SRT1720 on the responsiveness of Ewing's sarcoma (ES) cells to the chemotherapeutic drugs etoposide and vincristine. Because the effects of STACs can depend on the functionality of the tumor suppressor protein p53, we used three ES cell lines differing in their p53 status, i.e., wild-type p53 WE-68 cells, mutant p53 SK-ES-1 cells and p53 null SK-N-MC cells. Single agent and combination therapy effects were assessed by flow cytometric analyses of propidium iodide uptake and mitochondrial depolarization, by measuring caspase 3/7 activity and by gene expression profiling. When applied as single agents, both STACs were effective in ES cells irrespective of their p53 status. Strikingly, however, when applied in conjunction with cytostatic agents, the STACs displayed reverse effects: SRT1720 largely enhanced etoposide- and vincristine-induced cell death, while resveratrol inhibited it. Combination index analyses validated the antipodal impact of the STACs on the effectiveness of the chemotherapeutics. These findings suggest that the synthetic STAC SRT1720 may be useful to enhance the efficacy of anticancer therapy in ES. But they also suggest that the dietary intake of the natural STAC resveratrol may be detrimental during chemotherapy of ES.

  18. The Role of Reverse Logistics on the European Market

    OpenAIRE

    Irina Tobosaru; Irina Nicolau

    2009-01-01

    The Council of Logistics Management has published the first definition of reverse logistics in 1992: “The term reverse logistics refers to the role of logistics in recycling waste, in the distribution and the handling of dangerous materials. A broader definition includes in the reverse logistics, activities that have the purpose of reducing the resources, of recycling, replacing, reusing the materials and relocating them”. Reverse logistics can be also defined using as standard the definition...

  19. Structural optimization of N1-aryl-benzimidazoles for the discovery of new non-nucleoside reverse transcriptase inhibitors active against wild-type and mutant HIV-1 strains.

    Science.gov (United States)

    Monforte, Anna Maria; De Luca, Laura; Buemi, Maria Rosa; Agharbaoui, Fatima E; Pannecouque, Christophe; Ferro, Stefania

    2018-02-01

    Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are recommended components of preferred combination antiretroviral therapies used for the treatment of human immunodeficiency virus (HIV) infection. These regimens are extremely effective in suppressing virus replication. Recently, our research group identified some N 1 -aryl-2-arylthioacetamido-benzimidazoles as a novel class of NNRTIs. In this research work we report the design, the synthesis and the structure-activity relationship studies of new compounds (20-34) in which some structural modifications have been introduced in order to investigate their effects on reverse transcriptase (RT) inhibition and to better define the features needed to increase the antiviral activity. Most of the new compounds proved to be highly effective in inhibiting both RT enzyme at nanomolar concentrations and HIV-1 replication in MT4 cells with minimal cytotoxicity. Among them, the most promising N 1 -aryl-2-arylthioacetamido-benzimidazoles and N 1 -aryl-2-aryloxyacetamido-benzimidazoles were also tested toward a panel of single- and double-mutants strain responsible for resistance to NNRTIs, showing in vitro antiviral activity toward single mutants L100I, K103N, Y181C, Y188L and E138K. The best results were observed for derivatives 29 and 33 active also against the double mutants F227L and V106A. Computational approaches were applied in order to rationalize the potency of the new synthesized inhibitors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. On thermodynamic and microscopic reversibility

    International Nuclear Information System (INIS)

    Crooks, Gavin E

    2011-01-01

    The word 'reversible' has two (apparently) distinct applications in statistical thermodynamics. A thermodynamically reversible process indicates an experimental protocol for which the entropy change is zero, whereas the principle of microscopic reversibility asserts that the probability of any trajectory of a system through phase space equals that of the time reversed trajectory. However, these two terms are actually synonymous: a thermodynamically reversible process is microscopically reversible, and vice versa

  1. Reverse logistics in the Brazilian construction industry.

    Science.gov (United States)

    Nunes, K R A; Mahler, C F; Valle, R A

    2009-09-01

    In Brazil most Construction and Demolition Waste (C&D waste) is not recycled. This situation is expected to change significantly, since new federal regulations oblige municipalities to create and implement sustainable C&D waste management plans which assign an important role to recycling activities. The recycling organizational network and its flows and components are fundamental to C&D waste recycling feasibility. Organizational networks, flows and components involve reverse logistics. The aim of this work is to introduce the concepts of reverse logistics and reverse distribution channel networks and to study the Brazilian C&D waste case.

  2. Reversible Communicating Processes

    Directory of Open Access Journals (Sweden)

    Geoffrey Brown

    2016-02-01

    Full Text Available Reversible distributed programs have the ability to abort unproductive computation paths and backtrack, while unwinding communication that occurred in the aborted paths. While it is natural to assume that reversibility implies full state recovery (as with traditional roll-back recovery protocols, an interesting alternative is to separate backtracking from local state recovery. For example, such a model could be used to create complex transactions out of nested compensable transactions where a programmer-supplied compensation defines the work required to "unwind" a transaction. Reversible distributed computing has received considerable theoretical attention, but little reduction to practice; the few published implementations of languages supporting reversibility depend upon a high degree of central control. The objective of this paper is to demonstrate that a practical reversible distributed language can be efficiently implemented in a fully distributed manner. We discuss such a language, supporting CSP-style synchronous communication, embedded in Scala. While this language provided the motivation for the work described in this paper, our focus is upon the distributed implementation. In particular, we demonstrate that a "high-level" semantic model can be implemented using a simple point-to-point protocol.

  3. CONCEPTUAL ISSUES REGARDING REVERSE LOGISTICS

    Directory of Open Access Journals (Sweden)

    Ioana Olariu

    2013-12-01

    Full Text Available As the power of consumers is growing, the product return for customer service and customer retention has become a common practice in the competitive market, which propels the recent practice of reverse logistics in companies. Many firms attracted by the value available in the flow, have proactively participated in handling returned products at the end of their usefulness or from other parts of the product life cycle. Reverse logistics is the flow and management of products, packaging, components and information from the point of consumption to the point of origin. It is a collection of practices similar to those of supply chain management, but in the opposite direction, from downstream to upstream. It involves activities such as reuse, repair, remanufacture, refurbish, reclaim and recycle. For the conventional forward logistics systems, the flow starts upstream as raw materials, later as manufactured parts and components to be assembled and continues downstream to reach customers as final products to be disposed once they reach their economic or useful lives. In reverse logistics, the disposed products are pushed upstream to be repaired, remanufactured, refurbished, and disassembled into components to be reused or as raw material to be recycled for later use.

  4. Simultaneous measurement of cholesterol 7 alpha-hydroxylase activity by reverse-phase high-performance liquid chromatography using both endogenous and exogenous [4-14C]cholesterol as substrate

    International Nuclear Information System (INIS)

    Hylemon, P.B.; Studer, E.J.; Pandak, W.M.; Heuman, D.M.; Vlahcevic, Z.R.; Chiang, J.Y.

    1989-01-01

    The HPLC-spectrophotometric method for measuring cholesterol 7 alpha-hydroxylase activity was modified by using a C-18 reverse-phase column to separate 7 alpha-hydroxy-4-cholesten-3-one and 4-cholesten-3-one and by adding 7 beta-hydroxycholesterol to each reaction mixture as an internal recovery standard. With this method, we were able to simultaneously measure cholesterol 7 alpha-hydroxylase activity using endogenous cholesterol and exogenous [4- 14 C]cholesterol as substrate. Rat liver cytosol differentially stimulated (286%) the 7 alpha-hydroxylation of exogenous [4- 14 C]-cholesterol. In contrast, total cholesterol 7 alpha-hydroxylase activity was stimulated only 35% by cytosol. This method should prove useful for studying mechanisms of cholesterol delivery to cholesterol 7 alpha-hydroxylase

  5. Economic impact of reversion

    International Nuclear Information System (INIS)

    2005-01-01

    Estimations of the Norwegian hydropower production and various reversion models' market value have been made. The value of the Norwegian hydropower production until 01.01.2007 is estimated to about Nok 289 billion after taxes, or about 2,42 Nok/kWh medium production, given an expected future electricity price of around 0,25 Nok/kWh and a discount rate at 6,5 percent in nominal terms after taxes. The estimate is slightly above the level of prices for Norwegian hydropower plants in the last 8-10 years. The value of reversion in private plants which today have a limited licence time is estimated to Nok 5,5 billion. The value of reversion in public-owned Norwegian hydropower plants are about Nok 21 billion with a 60 year licence period from 01.01.2007, and about 12 billion for 75 years (ml)

  6. Reversible deep disposal

    International Nuclear Information System (INIS)

    2009-10-01

    This presentation, given by the national agency of radioactive waste management (ANDRA) at the meeting of October 8, 2009 of the high committee for the nuclear safety transparency and information (HCTISN), describes the concept of deep reversible disposal for high level/long living radioactive wastes, as considered by the ANDRA in the framework of the program law of June 28, 2006 about the sustainable management of radioactive materials and wastes. The document presents the social and political reasons of reversibility, the technical means considered (containers, disposal cavities, monitoring system, test facilities and industrial prototypes), the decisional process (progressive development and blocked off of the facility, public information and debate). (J.S.)

  7. Modulation of hepatic stellate cells and reversibility of hepatic fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Yu, E-mail: 1293363632@QQ.com [Faculty of Graduate Studies of Guangxi University of Chinese Medicine, Nanning 530001, Guangxi Zhuang Autonomous Region (China); Deng, Xin, E-mail: Hendly@163.com [Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, 10 East China Road, Nanning 530011, Guangxi Zhuang Autonomous Region (China); Liang, Jian, E-mail: lj99669@163.com [Guangxi University of Chinese Medicine, Nanning 530001, Guangxi Zhuang Autonomous Region (China)

    2017-03-15

    Hepatic fibrosis (HF) is the pathological component of a variety of chronic liver diseases. Hepatic stellate cells (HSC) are the main collagen-producing cells in the liver and their activation promotes HF. If HSC activation and proliferation can be inhibited, HF occurrence and development can theoretically be reduced and even reversed. Over the past ten years, a number of studies have addressed this process, and here we present a review of HSC modulation and HF reversal. - Highlights: • We present a review of the modulation of hepatic stellate cells (HSC) and reversibility of hepatic fibrosis (HF). • HSC are the foci of HF occurrence and development, HF could be prevented and treated by modulating HSC. • If HSC activation and proliferation can be inhibited, HF could theoretically be inhibited and even reversed. • Prevention or reversal of HSC activation, or promotion of HSC apoptosis, immune elimination, and senescence may prevent, inhibit or reverse HF.

  8. Reversal of target-specific oral anticoagulants

    Science.gov (United States)

    Siegal, D.M.; Cuker, Adam

    2014-01-01

    Target-specific oral anticoagulants (TSOACs) provide safe and effective anticoagulation for the prevention and treatment of thrombosis in a variety of clinical settings by interfering with the activity of thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban, edoxaban, betrixaban). Although TSOACs have practical advantages over vitamin K antagonists (VKAs), there are currently no antidotes to reverse their anticoagulant effect. Herein we summarize the available evidence for TSOAC reversal using nonspecific and specific reversal agents. We discuss important limitations of existing evidence, which is derived from studies in human volunteers, animal models and in vitro experiments. Studies evaluating the safety and efficacy of reversal agents on clinical outcomes such as bleeding and mortality in patients with TSOAC-associated bleeding are needed. PMID:24880102

  9. Synthesis of a mixed-model stationary phase derived from glutamine for HPLC separation of structurally different biologically active compounds: HILIC and reversed-phase applications.

    Science.gov (United States)

    Aral, Tarık; Aral, Hayriye; Ziyadanoğulları, Berrin; Ziyadanoğulları, Recep

    2015-01-01

    A novel mixed-mode stationary phase was synthesised starting from N-Boc-glutamine, aniline and spherical silica gel (4 µm, 60 Å). The prepared stationary phase was characterized by IR and elemental analysis. The new stationary phase bears an embedded amide group into phenyl ring, highly polar a terminal amide group and non-polar groups (phenyl and alkyl groups). At first, this new mixed-mode stationary phase was used for HILIC separation of four nucleotides and five nucleosides. The effects of different separation conditions, such as pH value, mobile phase and temperature, on the separation process were investigated. The optimum separation for nucleotides was achieved using HILIC isocratic elution with aqueous mobile phase and acetonitrile with 20°C column temperature. Under these conditions, the four nucleotides could be separated and detected at 265 nm within 14 min. Five nucleosides were separated under HILIC isocratic elution with aqueous mobile phase containing pH=3.25 phosphate buffer (10mM) and acetonitrile with 20°C column temperature and detected at 265 nm within 14 min. Chromatographic parameters as retention factor, selectivity, theoretical plate number and peak asymmetry factor were calculated for the effect of temperature and water content in mobile phase on the separation process. The new column was also tested for nucleotides and nucleosides mixture and six analytes were separated in 10min. The chromatographic behaviours of these polar analytes on the new mixed-model stationary phase were compared with those of HILIC columns under similar conditions. Further, phytohormones and phenolic compounds were separated in order to see influence of the new stationary phase in reverse phase conditions. Eleven plant phytohormones were separated within 13 min using RP-HPLC gradient elution with aqueous mobile phase containing pH=2.5 phosphate buffer (10mM) and acetonitrile with 20°C column temperature and detected at 230 or 278 nm. The best separation

  10. Thermosensory reversal effect quantified

    NARCIS (Netherlands)

    Bergmann Tiest, W.M.; Kappers, A.M.L.

    2008-01-01

    At room temperature, some materials feel colder than others due to differences in thermal conductivity, heat capacity and geometry. When the ambient temperature is well above skin temperature, the roles of 'cold' and 'warm' materials are reversed. In this paper, this effect is quantified by

  11. Thermosensory reversal effect quantified

    NARCIS (Netherlands)

    Bergmann Tiest, W.M.; Kappers, A.M.L.

    2008-01-01

    At room temperature, some materials feel colder than others due to differences in thermal conductivity, heat capacity and geometry. When the ambient temperature is well above skin temperature, the roles of ‘cold’ and ‘warm’ materials are reversed. In this paper, this effect is quantified by

  12. Time reversal communication system

    Science.gov (United States)

    Candy, James V.; Meyer, Alan W.

    2008-12-02

    A system of transmitting a signal through a channel medium comprises digitizing the signal, time-reversing the digitized signal, and transmitting the signal through the channel medium. The channel medium may be air, earth, water, tissue, metal, and/or non-metal.

  13. Engineering Encounters: Reverse Engineering

    Science.gov (United States)

    McGowan, Veronica Cassone; Ventura, Marcia; Bell, Philip

    2017-01-01

    This column presents ideas and techniques to enhance your science teaching. This month's issue shares information on how students' everyday experiences can support science learning through engineering design. In this article, the authors outline a reverse-engineering model of instruction and describe one example of how it looked in our fifth-grade…

  14. Sex Reversal in Birds.

    Science.gov (United States)

    Major, Andrew T; Smith, Craig A

    2016-01-01

    Sexual differentiation in birds is controlled genetically as in mammals, although the sex chromosomes are different. Males have a ZZ sex chromosome constitution, while females are ZW. Gene(s) on the sex chromosomes must initiate gonadal sex differentiation during embryonic life, inducing paired testes in ZZ individuals and unilateral ovaries in ZW individuals. The traditional view of avian sexual differentiation aligns with that expounded for other vertebrates; upon sexual differentiation, the gonads secrete sex steroid hormones that masculinise or feminise the rest of the body. However, recent studies on naturally occurring or experimentally induced avian sex reversal suggest a significant role for direct genetic factors, in addition to sex hormones, in regulating sexual differentiation of the soma in birds. This review will provide an overview of sex determination in birds and both naturally and experimentally induced sex reversal, with emphasis on the key role of oestrogen. We then consider how recent studies on sex reversal and gynandromorphic birds (half male:half female) are shaping our understanding of sexual differentiation in avians and in vertebrates more broadly. Current evidence shows that sexual differentiation in birds is a mix of direct genetic and hormonal mechanisms. Perturbation of either of these components may lead to sex reversal. © 2016 S. Karger AG, Basel.

  15. Elastomers with Reversible Nanoporosity

    DEFF Research Database (Denmark)

    Szewczykowski, Piotr Przemyslaw; Andersen, K.; Schulte, Lars

    2009-01-01

    nanostructure and displays liquid-filled cavities. Upon several cycles of swelling and drying the cavities open and close in a reversible fashion. When exposed to a nonsolvent, the material remains collapsed. This discriminating behavior of liquid-material interaction holds potential for the use...

  16. Understanding the Molecular Determinant of Reversible Human Monoamine Oxidase B Inhibitors Containing 2H-Chromen-2-One Core: Structure-Based and Ligand-Based Derived Three-Dimensional Quantitative Structure-Activity Relationships Predictive Models.

    Science.gov (United States)

    Mladenović, Milan; Patsilinakos, Alexandros; Pirolli, Adele; Sabatino, Manuela; Ragno, Rino

    2017-04-24

    Monoamine oxidase B (MAO B) catalyzes the oxidative deamination of aryalkylamines neurotransmitters with concomitant reduction of oxygen to hydrogen peroxide. Consequently, the enzyme's malfunction can induce oxidative damage to mitochondrial DNA and mediates development of Parkinson's disease. Thus, MAO B emerges as a promising target for developing pharmaceuticals potentially useful to treat this vicious neurodegenerative condition. Aiming to contribute to the development of drugs with the reversible mechanism of MAO B inhibition only, herein, an extended in silico-in vitro procedure for the selection of novel MAO B inhibitors is demonstrated, including the following: (1) definition of optimized and validated structure-based three-dimensional (3-D) quantitative structure-activity relationships (QSAR) models derived from available cocrystallized inhibitor-MAO B complexes; (2) elaboration of SAR features for either irreversible or reversible MAO B inhibitors to characterize and improve coumarin-based inhibitor activity (Protein Data Bank ID: 2V61 ) as the most potent reversible lead compound; (3) definition of structure-based (SB) and ligand-based (LB) alignment rule assessments by which virtually any untested potential MAO B inhibitor might be evaluated; (4) predictive ability validation of the best 3-D QSAR model through SB/LB modeling of four coumarin-based external test sets (267 compounds); (5) design and SB/LB alignment of novel coumarin-based scaffolds experimentally validated through synthesis and biological evaluation in vitro. Due to the wide range of molecular diversity within the 3-D QSAR training set and derived features, the selected N probe-derived 3-D QSAR model proves to be a valuable tool for virtual screening (VS) of novel MAO B inhibitors and a platform for design, synthesis and evaluation of novel active structures. Accordingly, six highly active and selective MAO B inhibitors (picomolar to low nanomolar range of activity) were disclosed as a

  17. Deep reversible storage. Safety options for the storage in deep geological formation - High-medium activity, long living wastes 2009 milestone

    International Nuclear Information System (INIS)

    2010-09-01

    This large document aims at presenting safety options which have been adopted for the current design status (notably for the installation architecture), elements of description of envisaged technical solutions and exploitation principles which are required for the control of risks (either internal or external) and uncertainties on a long term which could lead to radiological consequences for the project of storage of nuclear wastes in a deep geological formation. After a presentation of the context and of input data, this report discusses the principle of a modular construction and then discusses the safety approach. One part deals with risk analysis for surface installations and aims at showing how internal risks (handling, fire) and external risks (earthquake, plane crash) are taken into account in terms of design choices, processes and control measures. Another part deals with risk analysis for underground installations during the reversible exploitation phase (the considered risks are about the same as in the previous part). The next part addresses risk analysis after closing, and tries to describe how the location, storage construction elements and its architecture ensure a passive safety. Uncertainty management is presented in relationship with envisaged technical solutions and scientific knowledge advances. Additional elements (detailed study, researches and experimentations) for the establishment of the future creation authorization request are identified all along the report

  18. Purification and Characterization of a White Laccase with Pronounced Dye Decolorizing Ability and HIV-1 Reverse Transcriptase Inhibitory Activity from Lepista nuda

    Directory of Open Access Journals (Sweden)

    Mengjuan Zhu

    2016-03-01

    Full Text Available A strain LN07 with high laccase yield was identified as basidiomycete fungus Lepista nuda from which a white laccase without type I copper was purified and characterized. The laccase was a monomeric protein with a molecular mass of 56 kDa. Its N-terminal amino acid sequence was AIGPAADLHIVNKDISPDGF. Besides, eight inner peptide sequences were determined and lac4, lac5 and lac6 sequences were in the Cu2+ combination and conservation zones of laccases. HIV-1 reverse transcriptase was inhibited by the laccase with a half-inhibitory concentration of 0.65 μM. Cu2+ ions (1.5 mM enhanced the laccase production and the optimal pH and temperature of the laccase were pH 3.0 and 50 °C, respectively. The Km and Vmax of the laccase using ABTS as substrate were respectively 0.19 mM and 195 μM. Several dyes including laboratory dyes and textile dyes used in this study, such as Methyl red, Coomassie brilliant blue, Reactive brilliant blue and so on, were decolorized in different degrees by the purified laccase. By LC-MS analysis, Methyl red was structurally degraded by the laccase. Moreover, the laccase affected the absorbance at the maximum wavelength of many pesticides. Thus, the white laccase had potential commercial value for textile finishing and wastewater treatment.

  19. Study of Separation and Identification of the Active Ingredients in Gardenia jasminoides Ellis Based on a Two-Dimensional Liquid Chromatography by Coupling Reversed Phase Liquid Chromatography and Hydrophilic Interaction Liquid Chromatography.

    Science.gov (United States)

    Zhou, Xuan; Chen, Cen; Ye, Xiaolan; Song, Fenyun; Fan, Guorong; Wu, Fuhai

    2017-01-01

    In this paper, by coupling reversed phase liquid chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC), a two-dimensional liquid chromatography system was developed for separation and identification of the active ingredients in Gardenia jasminoides Ellis (GJE). By applying the semi-preparative C18 column as the first dimension and the core-shell column as the second dimension, a total of 896 peaks of GJE were separated. Among the 896 peaks, 16 active ingredients including geniposide, gardenoside, gardoside, etc. were identified by mass spectrometry analysis. The results indicated that the proposed two-dimensional RPLC/HILIC system was an effective method for the analysis of GJE and might hold a high potential to become a useful tool for analysis of other complex mixtures. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Reversible Activation of Halophilic β-lactamase from Methanol-Induced Inactive Form: Contrast to Irreversible Inactivation of Non-Halophilic Counterpart.

    Science.gov (United States)

    Tokunaga, Hiroko; Maeda, Junpei; Arakawa, Tsutomu; Tokunaga, Masao

    2017-06-01

    Effects of a water-miscible organic solvent, methanol, on the structure and activity of halophilic β-lactamase derived from Chromohalobacter sp.560 (HaBla), were investigated by means of circular dichroism (CD) measurement and enzymatic activity determination. Beta-lactamase activity was enhanced about 1.2-fold in the presence of 10-20% methanol. CD measurement of HaBla revealed different structures depending on the methanol concentration: native-like active form (Form I) in 10-20% methanol and methanol-induced inactive form at higher concentration (Form II in 40-60% and Form III in 75-80% methanol). Incubation of HaBla with 40% methanol led to the complete loss of activity within ~80 min accompanied by the formation of Form II, whose activity was recovered promptly up to ~80% of full activity upon dilution of the methanol concentration to 10%. In addition, when the protein concentration was sufficiently high (e.g., 0.7 mg/ml), HaBla activity of Form III in 75% methanol could be recovered in the same way (with slightly slower recovery rate), upon dilution of the methanol concentration. In contrast, non-halophilic β-lactamase from Escherichia coli K12 strain MG1655 (EcBla) was irreversibly denatured in the presence of 40% methanol. HaBla showed remarkable ability to renature from the methanol-induced inactive states.

  1. In Vitro Evaluation of Reversible and Time-Dependent Inhibitory Effects of Kalanchoe crenata on CYP2C19 and CYP3A4 Activities.

    Science.gov (United States)

    Awortwe, Charles; Manda, Vamshi K; Avonto, Cristina; Khan, Shabana I; Khan, Ikhlas A; Walker, Larry A; Bouic, Patrick J; Rosenkranz, Bernd

    2015-01-01

    Kalanchoe crenata popularly known as "dog's liver" is used in most African countries for the treatment of chronic diseases such as diabetes, asthma and HIV/AIDS related infections. The evaluation of K. crenata for herb-drug interactions has not been reported. This study therefore aims to evaluate the risk of K. crenata for herb-drug interaction in vitro. Crude methanol and fractions of K. crenata were incubated and preincubated with recombinant human CYP2C19 and CYP3A4. Comparative studies were conducted in both human liver microsomes and recombinant human CYP to ascertain the inhibition profile of the crude extract and the various fractions. The cocktail approach of recombinant human CYPs was conducted to confirm the inhibition potential of the fractions in the presence of other CYPs. The results showed significant time-dependent inhibition of tested samples on CYP3A4 with crude methanol (39KC), fractions 45A, 45B and 45D given IC50 fold decrease of 3.29, 2.26, 1.91 and 1.49, respective. Time dependent kinetic assessment of 39KC and 45D showed KI and kinact values for 39KC as 1.77 µg/mL and 0.091 min(-1) while that of 45D were 6.45 µg/mL and 0.024 min(-1), respectively. Determination of kinact based on IC50 calculations yielded 0.015 and 0.04 min(-1) for 39KC and 45D, respectively. Cocktail approach exhibited fold decreases in IC50 for all test fractions on CYP3A4 within the ranges of 2.10 - 4.10. At least one phytoconstituent in the crude methanol extract of Kalanchoe crenata is a reversible and time-dependent inhibitor of CYP3A4.

  2. Reversed field pinch diagnostics

    International Nuclear Information System (INIS)

    Weber, P.G.

    1986-01-01

    The Reversed Field Pinch (RFP) is a toroidal, axisymmetric magnetic confinement configuration characterized by a magnetic field configuration in which the toroidal magnetic field is of similar strength to the poloidal field, and is reversed at the edge compared to the center. The RFP routinely operates at high beta, and is a strong candidate for a compact fusion device. Relevant attributes of the configuration will be presented, together with an overview of present and planned experiments and their diagnostics. RFP diagnostics are in many ways similar to those of other magnetic confinement devices (such as tokamaks); these lectures will point out pertinent differences, and will present some diagnostics which provide special insights into unique attributes of the RFP

  3. Posterior Reversible Encephalopathy (PRES)

    International Nuclear Information System (INIS)

    Moron E, Fanny E; Diaz Marchan, Pedro

    2005-01-01

    The Posterior Reversible Encephalopathy Syndrome (PRES) is a clinical Syndrome composed of cephalea, alteration in vision and convulsions, usually observed in patients with sudden elevation of arterial pressure. The imagenologic evidence shows reversible vasogenic brain edema without stroke. Its location is predominantly posterior; it affects the cortex and the subcortical white matter of the occipital, parietal and temporal lobes. The treatment with antihypertensive drugs and the removing of immunosupressor medication are generally associated with complete neurological recovery; this is reflected also in the images which return to their basal condition. The untreated hypertension, on the other side, can result in a progressive defect of the autoregulation system of the central nervous system with cerebral hemorrhage, irreversible brain stroke, coma and death

  4. First indications of high slip rates on active reverse faults NW of Damascus, Syria, from observations of deformed Quaternary sediments: Implications for the partitioning of crustal deformation in the Middle Eastern region

    Science.gov (United States)

    Abou Romieh, Mohammad; Westaway, Rob; Daoud, Mohamad; Bridgland, David R.

    2012-05-01

    Recent research on rates of crustal shortening within the Palmyra Fold Belt (PFB) in Syria has drawn attention to the possibility that reverse faults near the city of Damascus, which adjoins the SW PFB, have significant slip rates. We infer that the Damascus Fault, directly adjacent to the city, has developed a throw of ~ 2500 m and report the discovery of the en echelon Bassimeh Fault, with a throw of ~ 1000 m, this fault being revealed by warping of the local bedrock and of a terrace, of inferred Late Pleistocene age, of the River Barada. We estimate that this set of faults became active circa 0.9 Ma, synchronous with changes to the pattern of faulting previously reported farther southwest in the northern Jordan Valley. Vertical slip rates on the Bassimeh and Damascus faults of ~ 1.1 and ~ 2.8 mm a- 1, respectively, are thus estimated. We also infer that large historical earthquakes, previously attributed to left-lateral faulting farther west on the Dead Sea Fault Zone (DSFZ), probably occurred on this set of reverse faults; these faults thus represent a significant hazard to the city of Damascus. Our observations indicate that as much as half of the northward motion of the Arabian plate, relative to the African plate, may be 'absorbed' by crustal shortening within the PFB, potentially explaining the low slip rate recently measured geodetically on the northern DSFZ in western Syria.

  5. Reversible infantile mitochondrial diseases.

    Science.gov (United States)

    Boczonadi, Veronika; Bansagi, Boglarka; Horvath, Rita

    2015-05-01

    Mitochondrial diseases are usually severe and progressive conditions; however, there are rare forms that show remarkable spontaneous recoveries. Two homoplasmic mitochondrial tRNA mutations (m.14674T>C/G in mt-tRNA(Glu)) have been reported to cause severe infantile mitochondrial myopathy in the first months of life. If these patients survive the first year of life by extensive life-sustaining measures they usually recover and develop normally. Another mitochondrial disease due to deficiency of the 5-methylaminomethyl-2-thiouridylate methyltransferase (TRMU) causes severe liver failure in infancy, but similar to the reversible mitochondrial myopathy, within the first year of life these infants may also recover completely. Partial recovery has been noted in some other rare forms of mitochondrial disease due to deficiency of mitochondrial tRNA synthetases and mitochondrial tRNA modifying enzymes. Here we summarize the clinical presentation of these unique reversible mitochondrial diseases and discuss potential molecular mechanisms behind the reversibility. Understanding these mechanisms may provide the key to treatments of potential broader relevance in mitochondrial disease, where for the majority of the patients no effective treatment is currently available.

  6. Positioning paper on reversibility

    International Nuclear Information System (INIS)

    2016-01-01

    After having recalled the legal framework adopted in 2006 for the deep geological storage of radioactive wastes, and briefly introduced the concept of reversibility, this publication presents the principle of geological storage, presents high and medium level and long life wastes, highlights the ethical necessity to deal with these radioactive wastes, outlines that geological storage is the generally admitted and adopted solution at the international level, and presents additional means implemented for radioactive waste management. It presents the Cigeo project as the technical answer to the issue of radioactive waste storage, describes the Cigeo development process, its current status and its development planning, and justifies the choice of this technical solution, notably from an ethical point of view. It addresses the issue of reversibility and proposes an overview of the various tools and means which aim at guaranteeing this reversibility. Appendices propose figures illustrating the Cigeo project and its development process, and a rather detailed Power Point presentation of the project by the ANDRA (history, object, planning, installations, and so on)

  7. Alpha-Adrenoceptor Antagonists Improve Memory by Activating -methyl-D-Aspartate-Induced Ion Currents in the Rat Hippocampus

    Directory of Open Access Journals (Sweden)

    Chang Hee Kim

    2015-12-01

    Full Text Available Purpose: Alpha1 (α1-adrenoceptor antagonists are widely used to treat lower urinary tract symptoms. These drugs not only act on peripheral tissues, but also cross the blood-brain barrier and affect the central nervous system. Therefore, α1-adrenoceptor antagonists may enhance brain functions. In the present study, we investigated the effects of tamsulosin, an α1-adrenoceptor antagonist, on short-term memory, as well as spatial learning and memory, in rats. Methods: The step-down avoidance test was used to evaluate short-term memory, and an eight-arm radial maze test was used to evaluate spatial learning and memory. TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining was performed in order to evaluate the effect of tamsulosin on apoptosis in the hippocampal dentate gyrus. Patch clamp recordings were used to evaluate the effect of tamsulosin on ionotropic glutamate receptors, such as N-methyl-D-aspartate (NMDA, amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA, and kainate receptors, in hippocampal CA1 neurons. Results: Tamsulosin treatment improved short-term memory, as well as spatial learning and memory, without altering apoptosis. The amplitudes of NMDA-induced ion currents were dose-dependently increased by tamsulosin. However, the amplitudes of AMPA- and kainate-induced ion currents were not affected by tamsulosin. Conclusions: Tamsulosin enhanced memory function by activating NMDA receptor-mediated ion currents in the hippocampus without initiating apoptosis. The present study suggests the possibility of using tamsulosin to enhance memory under normal conditions, in addition to its use in treating overactive bladder.

  8. Remote Whispering Applying Time Reversal

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Brian Eric [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-07-16

    The purpose of this project was to explore the use of time reversal technologies as a means for communication to a targeted individual or location. The idea is to have the privacy of whispering in one’s ear, but to do this remotely from loudspeakers not located near the target. Applications of this work include communicating with hostages and survivors in rescue operations, communicating imaging and operational conditions in deep drilling operations, monitoring storage of spent nuclear fuel in storage casks without wires, or clandestine activities requiring signaling between specific points. This technology provides a solution in any application where wires and radio communications are not possible or not desired. It also may be configured to self calibrate on a regular basis to adjust for changing conditions. These communications allow two people to converse with one another in real time, converse in an inaudible frequency range or medium (i.e. using ultrasonic frequencies and/or sending vibrations through a structure), or send information for a system to interpret (even allowing remote control of a system using sound). The time reversal process allows one to focus energy to a specific location in space and to send a clean transmission of a selected signal only to that location. In order for the time reversal process to work, a calibration signal must be obtained. This signal may be obtained experimentally using an impulsive sound, a known chirp signal, or other known signals. It may also be determined from a numerical model of a known environment in which the focusing is desired or from passive listening over time to ambient noise.

  9. A Novel Aspartic Protease with HIV-1 Reverse Transcriptase Inhibitory Activity from Fresh Fruiting Bodies of the Wild Mushroom Xylaria hypoxylon

    Directory of Open Access Journals (Sweden)

    Qing-Xiu Hu

    2012-01-01

    Full Text Available A novel aspartic protease with HIV-1 RT inhibitory activity was isolated and characterized from fruiting bodies of the wild mushroom Xylaria hypoxylon. The purification protocol comprised distilled water homogenization and extraction step, three ion exchange chromatographic steps (on DEAE-cellulose, Q-Sepharose, and CM-cellulose in succession, and final purification was by FPLC on Superdex 75. The protease was adsorbed on all the three ion exchangers. It was a monomeric protein with a molecular mass of 43 kDa as estimated by SDS-PAGE and FPLC. Its N-terminal amino acid sequence was HYTELLSQVV, which exhibited no sequence homology to other proteases reported. The activity of the protease was adversely affected by Pepstatin A, indicating that it is an aspartic protease. The protease activity was maximal or nearly so in the pH range 6–8 and in the temperature range 35–60°C. The purified enzyme exhibited HIV-1 RT inhibitory activity with an IC50 value of 8.3 μM, but was devoid of antifungal, ribonuclease, and hemagglutinating activities.

  10. Status of time reversal invariance

    International Nuclear Information System (INIS)

    Henley, E.M.

    1989-01-01

    Time Reversal Invariance is introduced, and theories for its violation are reviewed. The present experimental and theoretical status of Time Reversal Invariance and tests thereof will be presented. Possible future tests will be discussed. 30 refs., 2 figs., 1 tab

  11. Introduction to time reversal theory

    International Nuclear Information System (INIS)

    Henley, E.M.

    1987-01-01

    Theory and reaction mechanisms relevant to time reversal invariance are reviewed. Consequences of time reversal invariance are presented under the headings of CP tests, electromagnetic moments, weak emissions or absorptions, and scattering reactions. 8 refs., 4 figs

  12. Higher Doses of (+)MK-801 (Dizocilpine) Induced Mortality and Procedural but Not Cognitive Deficits in Delayed Testing in the Active Place Avoidance With Reversal on the Carousel

    Czech Academy of Sciences Publication Activity Database

    Lobellová, Veronika; Brichtová, Eva; Petrásek, Tomáš; Valeš, Karel; Stuchlík, Aleš

    2015-01-01

    Roč. 64, č. 2 (2015), s. 269-275 ISSN 0862-8408 R&D Projects: GA MZd(CZ) NT13386 Institutional support: RVO:67985823 Keywords : Dizocilpine * (+)MK-801 * active place avoidance * Carousel * Long-Evans rats Subject RIV: FH - Neurology Impact factor: 1.643, year: 2015

  13. Activity coefficients, interfacial tensions and retention in reversed-phase liquid chormatography on LiChrosorb RP-18 with methanol-water mixtures

    NARCIS (Netherlands)

    Hammers, W.E.; Meurs, G.J.; Ligny, C.L. de

    1982-01-01

    Literature data on activity coefficients of various solutes in water, of some tetraalkyl compounds in methanol-water mixture and of water in organic solvents have been correlated with the product of the molecular surface area of the solute and the solute-solvent interfacial tension at ambient

  14. AN OVERVIEW ON RETAIL REVERSE LOGISTICS

    Directory of Open Access Journals (Sweden)

    Ioana Olariu

    2014-07-01

    Full Text Available This article is a theoretical approach on retail reverse logistics. Environmental concern and the current marketing strategy have spurred retailers to implement strategies to facilitate product returns from end customers. Reverse logistics, indicating the process of this return flow, encompasses such activities as the movement of returned products, facilities to accommodate returned items, and overall remedy process for returned items. The retail industry, under great competitive pressure, has used return policies as a competitive weapon. Grocery retailers were the first to begin to focus serious attention on the problem of returns and to develop reverse logistics innovations. Grocery retailers first developed innovations such as reclamation centers. Reclamation centers, in turn, led to the establishment of centralized return centers. Centralizing returns has led to significant benefits for most firms that have implemented them. Over the last several years, retailers have consolidated. Now, more than ever, reverse logistics is seen as being important. This reverse distribution activity can be crucial to the survival of companies, because the permanent goodwill of the company is at stake. Businesses succeed because they respond to both external and internal changes and adjust in an effective manner to remain competitive.

  15. The Causes of Preference Reversal.

    OpenAIRE

    Tversky, Amos; Slovic, Paul; Kahneman, Daniel

    1990-01-01

    Observed preference reversal cannot be adequately explained by violations of independence, the reduction axiom, or transitivity. The primary cause of preference reversal is the failure of procedure invariance, especially the overpricing of low-probability, high-payoff bets. This result violates regret theory and generalized (nonindependent) utility models. Preference reversal and a new reversal involving time preferences are explained by scale compatibility, which implies that payoffs are wei...

  16. Geomagnetic Field During a Reversal

    Science.gov (United States)

    Heirtzler, J. R.

    2003-01-01

    It has frequently been suggested that only the geomagnetic dipole, rather than higher order poles, reverse during a geomagnetic field reversal. Under this assumption the geomagnetic field strength has been calculated for the surface of the Earth for various steps of the reversal process. Even without an eminent a reversal of the field, extrapolation of the present secular change (although problematic) shows that the field strength may become zero in some geographic areas within a few hundred years.

  17. A Study on Reverse Logistics

    OpenAIRE

    Reddy, Dhananjaya

    2011-01-01

    In the competitive world of manufacturing, companies are often searching for new ways to improve their process, customer satisfaction and stay ahead in the game with their competitors. Reverse logistics has been considered a strategy to bring these things to life for the past decade or so. This thesis work tries to shed some light on the basics of reverse logistics and how reverse logistics can be used as a management strategy. This paper points out the fundamentals of reverse logistics and l...

  18. mTOR inhibition in macrophages of asymptomatic HIV+ persons reverses the decrease in TLR4-mediated TNFα release through prolongation of MAPK pathway activation1

    Science.gov (United States)

    Li, Xin; Han, Xinbing; Llano, Juliana; Bole, Medhavi; Zhou, Xiuqin; Swan, Katharine; Anandaiah, Asha; Nelson, Benjamin; Patel, Naimish R.; Reinach, Peter S.; Koziel, Henry; Tachado, Souvenir D.

    2011-01-01

    Toll-like receptor 4 (TLR4) mediated signaling is significantly impaired in macrophages from HIV+ persons predominantly due to altered MyD88-dependent pathway signaling caused in part by constitutive activation of PI3K. Here we assessed in these macrophages if the blunted increase in TLR4-mediated TNFα release induced by lipid A are associated with PI3K-induced upregulation of mammalian target of rapamycin (mTOR) activity. mTOR inhibition with rapamycin enhanced TLR4-mediated TNFα release, but instead suppressed anti-inflammatory IL-10 release. Targeted gene silencing of mTOR in macrophages resulted in lipid A-induced TNFα and IL-10 release patterns similar to those induced by rapamycin. Rapamycin restored MyD88-IRAK interaction in a dose-dependent manner. Targeted gene silencing of MyD88 (shRNA) and mTOR (RNAi) inhibition resulted in TLR4-mediated p70s6K activation and enhanced TNFα release, whereas IL-10 release was inhibited in both silenced and non-silenced HIV+ macrophages. Furthermore, mTOR inhibition augmented lipid A-induced TNFα release through enhanced and prolonged phosphorylation of ERK1/2 and JNK1/2 MAP kinases, which was associated with time-dependent MKP-1 destabilization. Taken together, impaired TLR4-mediated TNFα release in HIV+ macrophages is attributable in part to mTOR activation by constitutive PI3K expression in a MyD88-dependent signaling pathway. These changes result in MKP-1 stabilization, which shortens and blunts MAP kinase activation. mTOR inhibition may serve as a potential therapeutic target to upregulate macrophage innate immune host defense responsiveness in HIV+ persons. PMID:22025552

  19. Exercise prescription to reverse frailty.

    Science.gov (United States)

    Bray, Nick W; Smart, Rowan R; Jakobi, Jennifer M; Jones, Gareth R

    2016-10-01

    Frailty is a clinical geriatric syndrome caused by physiological deficits across multiple systems. These deficits make it challenging to sustain homeostasis required for the demands of everyday life. Exercise is likely the best therapy to reverse frailty status. Literature to date suggests that pre-frail older adults, those with 1-2 deficits on the Cardiovascular Health Study-Frailty Phenotype (CHS-frailty phenotype), should exercise 2-3 times a week, for 45-60 min. Aerobic, resistance, flexibility, and balance training components should be incorporated but resistance and balance activities should be emphasized. On the other hand, frail (CHS-frailty phenotype ≥ 3 physical deficits) older adults should exercise 3 times per week, for 30-45 min for each session with an emphasis on aerobic training. During aerobic, balance, and flexibility training, both frail and pre-frail older adults should work at an intensity equivalent to a rating of perceived exertion of 3-4 ("somewhat hard") on the Borg CR10 scale. Resistance-training intensity should be based on a percentage of 1-repetition estimated maximum (1RM). Program onset should occur at 55% of 1RM (endurance) and progress to higher intensities of 80% of 1RM (strength) to maximize functional gains. Exercise is the medicine to reverse or mitigate frailty, preserve quality of life, and restore independent functioning in older adults at risk of frailty.

  20. Geomagnetic Reversals during the Phanerozoic.

    Science.gov (United States)

    McElhinny, M W

    1971-04-09

    An antalysis of worldwide paleomagnetic measurements suggests a periodicity of 350 x 10(6) years in the polarity of the geomagnetic field. During the Mesozoic it is predominantly normal, whereas during the Upper Paleozoic it is predominantly reversed. Although geomagnetic reversals occur at different rates throughout the Phanerozoic, there appeaars to be no clear correlation between biological evolutionary rates and reversal frequency.

  1. Reversible brazing process

    Science.gov (United States)

    Pierce, Jim D.; Stephens, John J.; Walker, Charles A.

    1999-01-01

    A method of reversibly brazing surfaces together. An interface is affixed to each surface. The interfaces can be affixed by processes such as mechanical joining, welding, or brazing. The two interfaces are then brazed together using a brazing process that does not defeat the surface to interface joint. Interfaces of materials such as Ni-200 can be affixed to metallic surfaces by welding or by brazing with a first braze alloy. The Ni-200 interfaces can then be brazed together using a second braze alloy. The second braze alloy can be chosen so that it minimally alters the properties of the interfaces to allow multiple braze, heat and disassemble, rebraze cycles.

  2. Dehydration induced loss of photosynthesis in Arabidopsis leaves during senescence is accompanied by the reversible enhancement in the activity of cell wall β-glucosidase.

    Science.gov (United States)

    Patro, Lichita; Mohapatra, Pranab Kishor; Biswal, Udaya Chand; Biswal, Basanti

    2014-08-01

    The physiology of loss of photosynthetic production of sugar and the consequent cellular sugar reprogramming during senescence of leaves experiencing environmental stress largely remains unclear. We have shown that leaf senescence in Arabidopsis thaliana causes a significant reduction in the rate of oxygen evolution and net photosynthetic rate (Pn). The decline in photosynthesis is further aggravated by dehydration. During dehydration, primary photochemical reaction of thylakoids and net photosynthesis decrease in parallel with the increase in water deficit. Senescence induced loss in photosynthesis is accompanied by a significant increase in the activity of cell wall hydrolyzing enzyme such as β-glucosidase associated with cell wall catabolism. The activity of this enzyme is further enhanced when the senescing leaves experience dehydration stress. It is possible that both senescence and stress separately or in combination result in the loss in photosynthesis which could be a signal for an enhancement in the activity of β-glucosidase that breaks down cell wall polysaccharides to sugar to sustain respiration for metabolic activities of plants experiencing stress. Thus dehydration response of cell wall hydrolases of senescing leaves is considered as plants' strategy to have cell wall polysaccharides as an alternative energy source for completion of energy requiring senescence process, stress survival and maintenance of recovery potential of energy deficit cells in the background of loss in photosynthesis. Withdrawal of stress (rehydration) distinctly exhibits recovery of photosynthesis and suppression of enzyme activity. Retention of the signaling for sugar reprogramming through breakdown of cell wall polysaccharides in the senescing leaves exposed to severe drought stress suggests that senescing leaves like mature ones possess potential for stress recovery. The precise mechanism of stress adaptation of senescing leaves is yet to be known. A significant

  3. Impaired insulin activation and dephosphorylation of glycogen synthase in skeletal muscle of women with polycystic ovary syndrome is reversed by pioglitazone treatment

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Højlund, Kurt; Andersen, Nicoline Resen

    2008-01-01

    CONTEXT: Insulin resistance is a major risk factor for type 2 diabetes in women with polycystic ovary syndrome (PCOS). The molecular mechanisms underlying reduced insulin-mediated glycogen synthesis in skeletal muscle of patients with PCOS have not been established. SUBJECTS AND METHODS: We...... metabolically characterized by euglycemic-hyperinsulinemic clamps and indirect calorimetry. RESULTS: Reduced insulin-mediated glucose disposal (P .... No significant abnormalities in GSK-3alpha or -3beta were found in PCOS subjects. Pioglitazone treatment improved insulin-stimulated glucose metabolism and GS activity in PCOS (all P

  4. Contextual influences on reverse knowledge transfer

    DEFF Research Database (Denmark)

    Søberg, Peder Veng

    2010-01-01

    Further development of theories about how contextual factors influence the beneficial reverse knowledge transfer from subsidiary to head quarters in disparate national country contexts, is the aim of our study. Earlier studies do not fully capture the different effects national country cultures can....... A proposition model is developed where the dependent variable is beneficial reverse knowledge transfer. The independent variables are: higher relative knowledge level in subsidiaty than in HQ, authority respect, activity fit with contextual learning preference. The conclusion suggest that different contexts...

  5. Reversibly Bistable Flexible Electronics

    KAUST Repository

    Alfaraj, Nasir

    2015-05-01

    Introducing the notion of transformational silicon electronics has paved the way for integrating various applications with silicon-based, modern, high-performance electronic circuits that are mechanically flexible and optically semitransparent. While maintaining large-scale production and prototyping rapidity, this flexible and translucent scheme demonstrates the potential to transform conventionally stiff electronic devices into thin and foldable ones without compromising long-term performance and reliability. In this work, we report on the fabrication and characterization of reversibly bistable flexible electronic switches that utilize flexible n-channel metal-oxide-semiconductor field-effect transistors. The transistors are fabricated initially on rigid (100) silicon substrates before they are peeled off. They can be used to control flexible batches of light-emitting diodes, demonstrating both the relative ease of scaling at minimum cost and maximum reliability and the feasibility of integration. The peeled-off silicon fabric is about 25 µm thick. The fabricated devices are transferred to a reversibly bistable flexible platform through which, for example, a flexible smartphone can be wrapped around a user’s wrist and can also be set back to its original mechanical position. Buckling and cyclic bending of such host platforms brings a completely new dimension to the development of flexible electronics, especially rollable displays.

  6. Compaction of LiBH4-LiAlH4 nanoconfined in activated carbon nanofibers: Dehydrogenation kinetics, reversibility, and mechanical stability during cycling

    DEFF Research Database (Denmark)

    Plerdsranoy, Praohatsorn; Javadian-Deylami, Seyd Payam; Jensen, Nicholai Daugaard

    2017-01-01

    To enhance volumetric hydrogen capacity for on-board fuel cells, compaction of LiAlH4-LiBH4 nanoconfined in activated carbon nanofibers (ACNF) is for the first time proposed. Loose powders of milled and nanoconfined LiAlH4-LiBH4 samples are compacted under 976 MPa to obtain the pellet samples...... with thickness and diameter of ∼1.20–1.30 and 8.0 mm, respectively. Dehydrogenation temperature of milled LiAlH4-LiBH4 increases from 415 to 434 °C due to compaction, while those of both compacted and loose powder samples of nanoconfined LiAlH4-LiBH4 are lower at comparable temperature of 330–335 °C. Hydrogen...

  7. Alterations on the morphology, nitric oxide synthesis and activity of platelets reproduced in rats as possible biomarkers for depression are reversed by fluoxetine.

    Science.gov (United States)

    González-Trujano, María Eva; Alvarado-Vásquez, Noé; Mendoza-Sotelo, José; López, Guadalupe; Estrada-Camarena, Erika; Martínez-Mota, Lucia; Moreno, Julia

    2012-08-01

    Biochemical markers associated with the prognosis of depression in humans are being described in the literature, whereas experimental studies in animal models in search for antidepressant strategies are lacking. The aim of this study was to evaluate platelet morphology, platelet activity and nitric oxide (NO) synthesis as possible biomarkers of depressive-like behavior by using FST alone and in the presence of fluoxetine. Naïve rats were compared to those receiving vehicle or fluoxetine at 10mg/kg i.p. in acute, subchronic and chronic administration in the FST. After behavioral assessment, platelets were isolated from blood samples and analyzed by flow cytometry to determine the platelet mitochondrial membrane potential and NO synthesis. In addition, HPLC and electron microscopy were used to examine 5-HT and tryptophan levels and morphology of platelets, respectively. Rats receiving vehicle and exposed to FST showed depressive-like behavior at all the times tested; after chronic FST rats showed a similar pattern of alteration in platelet morphology and in the studied as possible biochemical markers as those previously recognized in depressive humans. Depressive-like behavior in rats exposed to FST was prevented in the presence of fluoxetine administration at all the times tested and associated with the prevention of alterations in platelet morphology, platelet activity and NO synthesis, and/or in 5-HT concentrations. The results of the present study suggest that platelet function and morphology might be relevant markers for the prognosis of depression and the search for functional treatments. Besides, the relevance of FST as model to study this psychiatric illness is reinforced. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Piper sarmentosum Roxb. produces antidepressant-like effects in rodents, associated with activation of the CREB-BDNF-ERK signaling pathway and reversal of HPA axis hyperactivity.

    Science.gov (United States)

    Li, Qing; Qu, Fa-Lin; Gao, Yue; Jiang, Yi-Ping; Rahman, Khalid; Lee, Kuo-Hsiung; Han, Ting; Qin, Lu-Ping

    2017-03-06

    There are many plants of genus Piper which have been reported to induce antidepressant-like effects, Piper sarmentosum (PS) is one of them. PS is a Chinese herbal medicine and a traditional edible vegetable. In the present study, the antidepressant-like effects of PS extracts and the ethyl acetate fraction of PS extracts (PSY) were assessed using the open field test (OFT), forced swimming test (FST), and tail suspension test (TST) in mice. Furthermore, we applied a 4 consecutive weeks of chronic unpredictable mild stress (CUMS) as a model of depression in rats, followed by a sucrose preference test. Then we examined the possible mechanisms of this action. The activity of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated by detecting the serum corticosterone (CORT) concentrations, and the protein expression levels of brain-derived neurotrophic factor (BDNF), the phosphorylated form CREB and ERK1/2 were detected by qRT-PCR or Western blot. The results showed that PS extracts (100, 200mg/kg) and PSY (12.5, 25, 50mg/kg) treatment produced antidepressant-like effects in mice similar to fluoxetine (20mg/kg), indicated by the reduced immobility time in the FST and TST, while both had no influence on the locomotor activity in the OFT. PSY treatment significantly increased sucrose preference and reduced serum CORT levels in CUMS rats. Moreover, PSY up-regulated BDNF protein levels, and increased CREB and ERK phosphorylation levels in the hippocampus on CUMS rats. These findings suggest that the antidepressant-like effects of PS extracts and PSY are mediated, at least in part, by modulating HPA axis, BDNF, CREB and ERK phosphorylation and expression in the hippocampus. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  9. Pattern-reversal electroretinograms in unilateral glaucoma.

    Science.gov (United States)

    Wanger, P; Persson, H E

    1983-06-01

    Pattern-reversal and flash electroretinograms (ERG) and oscillatory potentials (OP) were recorded from 11 patients with unilateral glaucoma. All glaucomatous eyes had reduced amplitudes both compared to the opposite eye in the same patient and to reference values. In 10 of the 11 cases this reduction was below the level of normal variation. The difference in pattern-reversal ERG amplitude means from glaucomatous and opposite eyes was statistically significant. No differences were observed in flash ERGs or OPs. The histopathologic correlate to the visual field defects in glaucoma is retinal ganglion cell degeneration. The present electrophysiologic findings support the view, based on results from animal experiments, that the pattern-reversal ERG reflects ganglion cell activity.

  10. Reversible posterior leukoencephalopathy syndrome

    International Nuclear Information System (INIS)

    Lee, Eun Ja; Yu, Won Jong; Ahn, Kook Jin; Jung, So Lyung; Lee, Yeon Soo; Kim, Ji Chang; Kang, Si Won; Song, Chang Joon; Song, Soon-Young; Koo, Ja Hong; Kim, Man Deuk

    2001-01-01

    To review reversible posterior leukoencephalopathy syndrome. We reviewed 22 patients (M:F=3:19; age, 17-46 years) with the characteristic clinical and imaging features of reversible posterior leukoencephalopathy syndrome. All underwent brain MRI, and in three cases both CT and MRI were performed. In one, MRA was obtained, and in eleven, follow-up MR images were obtained. We evaluated the causes of this syndrome, its clinical manifestations, and MR findings including the locations of lesions, the presence or absence of contrast enhancement, and the changes seen at follow-up MRI. Of the 22 patients, 13 had eclampsia (six during pregnancy and seven during puerperium). Four were receiving immunosuppressive therapy (three, cyclosporine ; one, FK 506). Four suffered renal failure and one had complicated migraine. The clinical manifestations included headache (n=12), visual disturbance (n=13), seizure (n=15), focal neurologic sign (n=3), and altered mental status (n=2). Fifteen patients had hypertension and the others normotension. MRI revealed that lesions were bilateral (n=20) or unilateral (n=2). In all patients the lesion was found in the cortical and subcortical areas of the parieto-occipital lobes ; other locations were the basal ganglia (n=9), posterior temporal lobe (n=8), frontal lobe (n=5), cerebellum (n=5), pons (n=2), and thalamus (n=1). All lesions were of high signal intensity on T2-weighted images, and of iso to low intensity on T1-weighted images. One was combined with acute hematoma in the left basal ganglia. In eight of 11 patients who underwent postcontrast T1-weighted MRI, there was no definite enhancement ; in one, enhancement was mild, and in tow, patchy. CT studies showed low attenuation, and MRA revealed mild vasospasm. The symptoms of all patients improved. Follow-up MRI in nine of 11 patients depicted complete resolution of the lesions ; in two, small infarctions remained but the extent of the lesions had decreased. Reversible posterior

  11. Reversible posterior leukoencephalopathy syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Ja; Yu, Won Jong; Ahn, Kook Jin; Jung, So Lyung; Lee, Yeon Soo; Kim, Ji Chang; Kang, Si Won [The Catholic Univ. of Korea, Taejon (Korea, Republic of); Song, Chang Joon [Chungnam National Univ. School of Medicine, Cheonju (Korea, Republic of); Song, Soon-Young; Koo, Ja Hong [Kwandong Univ. College of Medicine, Myungji Hospital, Seoul (Korea, Republic of); Kim, Man Deuk [College of Medicine Pochon CHA Univ., Seoul (Korea, Republic of)

    2001-10-01

    To review reversible posterior leukoencephalopathy syndrome. We reviewed 22 patients (M:F=3:19; age, 17-46 years) with the characteristic clinical and imaging features of reversible posterior leukoencephalopathy syndrome. All underwent brain MRI, and in three cases both CT and MRI were performed. In one, MRA was obtained, and in eleven, follow-up MR images were obtained. We evaluated the causes of this syndrome, its clinical manifestations, and MR findings including the locations of lesions, the presence or absence of contrast enhancement, and the changes seen at follow-up MRI. Of the 22 patients, 13 had eclampsia (six during pregnancy and seven during puerperium). Four were receiving immunosuppressive therapy (three, cyclosporine ; one, FK 506). Four suffered renal failure and one had complicated migraine. The clinical manifestations included headache (n=12), visual disturbance (n=13), seizure (n=15), focal neurologic sign (n=3), and altered mental status (n=2). Fifteen patients had hypertension and the others normotension. MRI revealed that lesions were bilateral (n=20) or unilateral (n=2). In all patients the lesion was found in the cortical and subcortical areas of the parieto-occipital lobes ; other locations were the basal ganglia (n=9), posterior temporal lobe (n=8), frontal lobe (n=5), cerebellum (n=5), pons (n=2), and thalamus (n=1). All lesions were of high signal intensity on T2-weighted images, and of iso to low intensity on T1-weighted images. One was combined with acute hematoma in the left basal ganglia. In eight of 11 patients who underwent postcontrast T1-weighted MRI, there was no definite enhancement ; in one, enhancement was mild, and in tow, patchy. CT studies showed low attenuation, and MRA revealed mild vasospasm. The symptoms of all patients improved. Follow-up MRI in nine of 11 patients depicted complete resolution of the lesions ; in two, small infarctions remained but the extent of the lesions had decreased. Reversible posterior

  12. Combined Treatment of MCF-7 Cells with AICAR and Methotrexate, Arrests Cell Cycle and Reverses Warburg Metabolism through AMP-Activated Protein Kinase (AMPK and FOXO1.

    Directory of Open Access Journals (Sweden)

    Tamás Fodor

    Full Text Available Cancer cells are characterized by metabolic alterations, namely, depressed mitochondrial oxidation, enhanced glycolysis and pentose phosphate shunt flux to support rapid cell growth, which is called the Warburg effect. In our study we assessed the metabolic consequences of a joint treatment of MCF-7 breast cancer cells with AICAR, an inducer of AMP-activated kinase (AMPK jointly with methotrexate (MTX, a folate-analog antimetabolite that blunts de novo nucleotide synthesis. MCF7 cells, a model of breast cancer cells, were resistant to the individual application of AICAR or MTX, however combined treatment of AICAR and MTX reduced cell proliferation. Prolonged joint application of AICAR and MTX induced AMPK and consequently enhanced mitochondrial oxidation and reduced the rate of glycolysis. These metabolic changes suggest an anti-Warburg rearrangement of metabolism that led to the block of the G1/S and the G2/M transition slowing down cell cycle. The slowdown of cell proliferation was abolished when mitotropic transcription factors, PGC-1α, PGC-1β or FOXO1 were silenced. In human breast cancers higher expression of AMPKα and FOXO1 extended survival. AICAR and MTX exerts similar additive antiproliferative effect on other breast cancer cell lines, such as SKBR and 4T1 cells, too. Our data not only underline the importance of Warburg metabolism in breast cancer cells but nominate the AICAR+MTX combination as a potential cytostatic regime blunting Warburg metabolism. Furthermore, we suggest the targeting of AMPK and FOXO1 to combat breast cancer.

  13. Reversible Modification of Adenomatous Polyposis Coli (APC) with K63-linked Polyubiquitin Regulates the Assembly and Activity of the β-Catenin Destruction Complex

    Science.gov (United States)

    Tran, Hoanh; Polakis, Paul

    2012-01-01

    The adenomatous polyposis coli (APC) tumor suppressor forms a complex with Axin and GSK3β to promote the phosphorylation and degradation of β-catenin, a key co-activator of Wnt-induced transcription. Here, we establish that APC is modified predominantly with K63-linked ubiquitin chains when it is bound to Axin in unstimulated HEK293 cells. Wnt3a stimulation induced a time-dependent loss of K63-polyubiquitin adducts from APC, an effect synchronous with the dissociation of Axin from APC and the stabilization of cytosolic β-catenin. RNAi-mediated depletion of Axin or β-catenin, which negated the association between APC and Axin, resulted in the absence of K63-adducts on APC. Overexpression of wild-type and phosphodegron-mutant β-catenin, combined with analysis of thirteen human cancer cell lines that harbor oncogenic mutations in APC, Axin, or β-catenin, support the hypothesis that a fully assembled APC-Axin-GSK3β-phospho-β-catenin complex is necessary for the K63-polyubiquitylation of APC. Intriguingly, the degree of this modification on APC appears to correlate inversely with the levels of β-catenin in cells. Together, our results indicate that K63-linked polyubiquitin adducts on APC regulate the assembly and/or efficiency of the β-catenin destruction complex. PMID:22761442

  14. An Exploratory Analysis of Reverse Logistics in Flanders

    NARCIS (Netherlands)

    Verstrepen, Sven; Cruijssen, Frans; Brito, Marisa P De; Dullaert, Wout

    2007-01-01

    This paper reports on a reverse logistics survey of shippers and logistics service providers in Flanders, one of the leading logistics regions in Europe. We characterise the reverse logistics activities with respect to return reasons, recovery options, outsourcing, lifecycle length and value of

  15. Contribution of the reverse endoprosthesis to glenohumeral kinematics.

    NARCIS (Netherlands)

    Bergmann, J.H.M.; de Leeuw, M.; Janssen, T.W.J.; Veeger, H.E.J.; Willems, W.J.

    2008-01-01

    After placement of a reverse shoulder endoprosthesis, range of motion is usually still compromised. To what extent this occurs from limitation in motion of the reverse endoprosthesis is, however, unclear. We measured the motion pattern of 16 patients (18 shoulders) during three active and passive

  16. Reverse photoacoustic standoff spectroscopy

    Science.gov (United States)

    Van Neste, Charles W [Kingston, TN; Senesac, Lawrence R [Knoxville, TN; Thundat, Thomas G [Knoxville, TN

    2011-04-12

    A system and method are disclosed for generating a reversed photoacoustic spectrum at a greater distance. A source may emit a beam to a target and a detector measures signals generated as a result of the beam being emitted on the target. By emitting a chopped/pulsed light beam to the target, it may be possible to determine the target's optical absorbance by monitoring the intensity of light collected at the detector at different wavelengths. As the wavelength of light is changed, the target may absorb or reject each optical frequency. Rejection may increase the intensity at the sensing element and absorption may decrease the intensity. Accordingly, an identifying spectrum of the target may be made with the intensity variation of the detector as a function of illuminating wavelength.

  17. Reverse Osmosis Optimization

    Energy Technology Data Exchange (ETDEWEB)

    McMordie Stoughton, Kate; Duan, Xiaoli; Wendel, Emily M.

    2013-08-26

    This technology evaluation was prepared by Pacific Northwest National Laboratory on behalf of the U.S. Department of Energy’s Federal Energy Management Program (FEMP). ¬The technology evaluation assesses techniques for optimizing reverse osmosis (RO) systems to increase RO system performance and water efficiency. This evaluation provides a general description of RO systems, the influence of RO systems on water use, and key areas where RO systems can be optimized to reduce water and energy consumption. The evaluation is intended to help facility managers at Federal sites understand the basic concepts of the RO process and system optimization options, enabling them to make informed decisions during the system design process for either new projects or recommissioning of existing equipment. This evaluation is focused on commercial-sized RO systems generally treating more than 80 gallons per hour.¬

  18. Reverse Osmosis Optimization

    Energy Technology Data Exchange (ETDEWEB)

    None

    2013-08-01

    This technology evaluation was prepared by Pacific Northwest National Laboratory on behalf of the U.S. Department of Energy’s Federal Energy Management Program (FEMP). The technology evaluation assesses techniques for optimizing reverse osmosis (RO) systems to increase RO system performance and water efficiency. This evaluation provides a general description of RO systems, the influence of RO systems on water use, and key areas where RO systems can be optimized to reduce water and energy consumption. The evaluation is intended to help facility managers at Federal sites understand the basic concepts of the RO process and system optimization options, enabling them to make informed decisions during the system design process for either new projects or recommissioning of existing equipment. This evaluation is focused on commercial-sized RO systems generally treating more than 80 gallons per hour.

  19. Sex Reversal in Amphibians.

    Science.gov (United States)

    Flament, Stéphane

    2016-01-01

    Amphibians have been widely used to study developmental biology due to the fact that embryo development takes place independently of the maternal organism and that observations and experimental approaches are easy. Some amphibians like Xenopus became model organisms in this field. In the first part of this article, the differentiation of the gonads in amphibians and the mechanisms governing this process are reviewed. In the second part, the state of the art about sex reversal, which can be induced by steroid hormones in general and by temperature in some species, is presented. Also information about pollutants found in the environment that could interfere with the development of the amphibian reproductive apparatus or with their reproductive physiology is given. Such compounds could play a part in the amphibian decline, since in the wild, many amphibians are endangered species. © 2016 S. Karger AG, Basel.

  20. Reverse translation of phase I biomarker findings links the activity of angiotensin-(1–7) to repression of hypoxia inducible factor-1α in vascular sarcomas

    International Nuclear Information System (INIS)

    Petty, W Jeffrey; Aklilu, Mebea; Varela, Victor A; Lovato, James; Savage, Paul D; Miller, Antonius A

    2012-01-01

    In a phase I study of angiotensin-(1–7) [Ang-(1–7)], clinical benefit was associated with reduction in plasma placental growth factor (PlGF) concentrations. The current study examines Ang-(1–7) induced changes in biomarkers according to cancer type and investigates mechanisms of action engaged in vitro. Plasma biomarkers were measured prior to Ang-(1–7) administration as well as 1, 2, 3, 4, and 6 hours after treatment. Tests for interaction were performed to determine the impact of cancer type on angiogenic hormone levels. If a positive interaction was detected, treatment-induced biomarker changes for individual cancer types were assessed. To investigate mechanisms of action, in vitro growth assays were performed using a murine endothelioma cell line (EOMA). PCR arrays were performed to identify and statistically validate genes that were altered by Ang-(1–7) treatment in these cells. Tests for interaction controlled for dose cohort and clinical response indicated a significant impact of cancer type on post-treatment VEGF and PlGF levels. Following treatment, PlGF levels decreased over time in patients with sarcoma (P = .007). Treatment of EOMA cells with increasing doses of Ang-(1–7) led to significant growth suppression at doses as low as 100 nM. PCR arrays identified 18 genes that appeared to have altered expression after Ang-(1–7) treatment. Replicate analyses confirmed significant changes in 8 genes including reduction in PlGF (P = .04) and hypoxia inducible factor 1α (HIF-1α) expression (P < .001). Ang-(1–7) has clinical and pre-clinical activity for vascular sarcomas that is linked to reduced HIF-1α and PlGF expression

  1. THE CLUSTER AND FIELD GALAXY ACTIVE GALACTIC NUCLEUS FRACTION AT z = 1-1.5: EVIDENCE FOR A REVERSAL OF THE LOCAL ANTICORRELATION BETWEEN ENVIRONMENT AND AGN FRACTION

    International Nuclear Information System (INIS)

    Martini, Paul; Miller, E. D.; Bautz, M.; Brodwin, M.; Stanford, S. A.; Gonzalez, Anthony H.; Hickox, R. C.; Stern, D.; Eisenhardt, P. R.; Galametz, A.; Norman, D.; Dey, A.; Jannuzi, B. T.; Murray, S.; Jones, C.; Brown, M. J. I.

    2013-01-01

    The fraction of cluster galaxies that host luminous active galactic nuclei (AGNs) is an important probe of AGN fueling processes, the cold interstellar medium at the centers of galaxies, and how tightly black holes and galaxies co-evolve. We present a new measurement of the AGN fraction in a sample of 13 clusters of galaxies (M ≥ 10 14 M ☉ ) at 1 A = 3.0 +2.4 -1.4 % for AGNs with a rest-frame, hard X-ray luminosity greater than L X, H ≥ 10 44 erg s –1 . This fraction is measured relative to all cluster galaxies more luminous than M * 3.6 (z) + 1, where M * 3.6 (z) is the absolute magnitude of the break in the galaxy luminosity function at the cluster redshift in the IRAC 3.6 μm bandpass. The cluster AGN fraction is 30 times greater than the 3σ upper limit on the value for AGNs of similar luminosity at z ∼ 0.25, as well as more than an order of magnitude greater than the AGN fraction at z ∼ 0.75. AGNs with L X, H ≥ 10 43 erg s –1 exhibit similarly pronounced evolution with redshift. In contrast to the local universe, where the luminous AGN fraction is higher in the field than in clusters, the X-ray and MIR-selected AGN fractions in the field and clusters are consistent at 1 < z < 1.5. This is evidence that the cluster AGN population has evolved more rapidly than the field population from z ∼ 1.5 to the present. This environment-dependent AGN evolution mimics the more rapid evolution of star-forming galaxies in clusters relative to the field.

  2. THE CLUSTER AND FIELD GALAXY ACTIVE GALACTIC NUCLEUS FRACTION AT z = 1-1.5: EVIDENCE FOR A REVERSAL OF THE LOCAL ANTICORRELATION BETWEEN ENVIRONMENT AND AGN FRACTION

    Energy Technology Data Exchange (ETDEWEB)

    Martini, Paul [Department of Astronomy and Center for Cosmology and Astroparticle Physics, Ohio State University, 140 West 18th Avenue, Columbus, OH 43210 (United States); Miller, E. D.; Bautz, M. [Kavli Institute for Astrophysics and Space Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 (United States); Brodwin, M. [Department of Physics and Astronomy, University of Missouri, 5110 Rockhill Road, Kansas City, MO 64110 (United States); Stanford, S. A. [Department of Physics, University of California, One Shields Avenue, Davis, CA 95616 (United States); Gonzalez, Anthony H. [Department of Astronomy, University of Florida, Gainesville, FL 32611 (United States); Hickox, R. C. [Department of Physics and Astronomy, Dartmouth College, 6127 Wilder Laboratory, Hanover, NH 03755 (United States); Stern, D.; Eisenhardt, P. R. [Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109 (United States); Galametz, A. [INAF-Osservatorio di Roma, Via Frascati 33, I-00040 Monteporzio (Italy); Norman, D.; Dey, A. [NOAO, 950 North Cherry Avenue, Tucson, AZ 85719 (United States); Jannuzi, B. T. [Department of Astronomy and Steward Observatory, University of Arizona, 933 North Cherry Avenue, Tucson, AZ 85721 (United States); Murray, S.; Jones, C. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Brown, M. J. I., E-mail: martini@astronomy.ohio-state.edu [School of Physics, Monash University, Clayton, Victoria 3800 (Australia)

    2013-05-01

    The fraction of cluster galaxies that host luminous active galactic nuclei (AGNs) is an important probe of AGN fueling processes, the cold interstellar medium at the centers of galaxies, and how tightly black holes and galaxies co-evolve. We present a new measurement of the AGN fraction in a sample of 13 clusters of galaxies (M {>=} 10{sup 14} M{sub Sun }) at 1 < z < 1.5 selected from the Spitzer/IRAC Shallow Cluster Survey, as well as the field fraction in the immediate vicinity of these clusters, and combine these data with measurements from the literature to quantify the relative evolution of cluster and field AGN from the present to z {approx} 3. We estimate that the cluster AGN fraction at 1 < z < 1.5 is f{sub A} = 3.0{sup +2.4}{sub -1.4}% for AGNs with a rest-frame, hard X-ray luminosity greater than L{sub X,{sub H}} {>=} 10{sup 44} erg s{sup -1}. This fraction is measured relative to all cluster galaxies more luminous than M{sup *}{sub 3.6}(z) + 1, where M{sup *}{sub 3.6}(z) is the absolute magnitude of the break in the galaxy luminosity function at the cluster redshift in the IRAC 3.6 {mu}m bandpass. The cluster AGN fraction is 30 times greater than the 3{sigma} upper limit on the value for AGNs of similar luminosity at z {approx} 0.25, as well as more than an order of magnitude greater than the AGN fraction at z {approx} 0.75. AGNs with L{sub X,{sub H}} {>=} 10{sup 43} erg s{sup -1} exhibit similarly pronounced evolution with redshift. In contrast to the local universe, where the luminous AGN fraction is higher in the field than in clusters, the X-ray and MIR-selected AGN fractions in the field and clusters are consistent at 1 < z < 1.5. This is evidence that the cluster AGN population has evolved more rapidly than the field population from z {approx} 1.5 to the present. This environment-dependent AGN evolution mimics the more rapid evolution of star-forming galaxies in clusters relative to the field.

  3. Reversible deep storage: reversibility options for storage in deep geological formations

    International Nuclear Information System (INIS)

    2009-01-01

    This report describes the definition approach to reversibility conditions, presents the main characteristics of high-activity and intermediate-activity long-lived wastes, describes the storage in deep geological formations (safety functions, general description of the storage centre), discusses the design options for the different types of wastes (container, storage module, handling processes, phenomenological analysis, monitoring arrangements) and the decision process in support reversibility (steering of the storage process, progressive development and step-by-step closing), and reports and discusses the researches concerning the memory of the storage site

  4. Disruption of Zebrafish Follicle-Stimulating Hormone Receptor (fshr) But Not Luteinizing Hormone Receptor (lhcgr) Gene by TALEN Leads to Failed Follicle Activation in Females Followed by Sexual Reversal to Males.

    Science.gov (United States)

    Zhang, Zhiwei; Lau, Shuk-Wa; Zhang, Lingling; Ge, Wei

    2015-10-01

    Gonadotropins are primary hormones that control vertebrate reproduction. In a recent study, we analyzed the impacts of FSH and LH on zebrafish reproduction by disrupting FSH and LH-β genes (fshb and lhb) using transcription activator-like effector nuclease (TALEN) technology. Using the same approach, we successfully deleted FSH and LH receptor genes (fshr and lhcgr) in the present study. In contrast to the deficiency of its cognate ligand FSH, the fshr-deficient females showed a complete failure of follicle activation with all ovarian follicles arrested at the primary growth-previtellogenic transition, which is the marker for puberty onset in females. Interestingly, after blockade at the primary growth stage for varying times, all females reversed to males, and all these males were fertile. In fshr-deficient males, spermatogenesis was normal in adults, but the initiation of spermatogenesis in juveniles was retarded. In contrast to fshr, the deletion of the lhcgr gene alone caused no obvious phenotypes in both males and females; however, double mutation of fshr and lhcgr resulted in infertile males. In summary, our results in the present study showed that Fshr was indispensable to folliculogenesis and the disruption of the fshr gene resulted in a complete failure of follicle activation followed by masculinization into males. In contrast, lhcgr does not seem to be essential to zebrafish reproduction in both males and females. Neither Fshr nor Lhcgr deficiency could phenocopy the deficiency of their cognate ligands FSH and LH, which is likely due to the fact that Fshr can be activated by both FSH and LH in the zebrafish.

  5. Detecting A Botnet By Reverse Engineering

    Directory of Open Access Journals (Sweden)

    Oesman Hendra Kelana

    2013-06-01

    Full Text Available Abstract— Botnet malware is a malicious program. Botnet that infects computers, called bots, will be controlled by a botmaster to do various things such as: spamming, phishing, keylogging Distributed Denial of Service (DDoS and other activities that are generally profitable to the owner of the bot (botmaster or those who use botnet services. The problem is that many computers have been controlled by botnets without the knowledge of the computer owner.  There are many ways to examine botnets, for example by studying the traffic from the botnet network, studying how botnets communicate to each, studying how each robot receives orders to do something, and so forth. Of the many methods, the most frequently and commonly used is the reverse engineering, where researchers study how a botnet works by botnet debugging. In this study the author tries to understand or research botnets by taking a type of botnet, namely Agobot, using reverse engineering.  One of the result of the research is that malware program files in general and in particular botnet has a technique to obscure the way that research using reverse engineering. Another result also shows that the botnet Agobot runs on computers by using the Windows service, and by changing the Windows registry so that every time the computer starts, Agobot always actively works in the computer memory. Keywords— Malware, Bot, Botnet, Botmaster, Agobot, Spam, Distributed Denial of Services, Identity Theft, Computer Security, Reverse Engineering, Debug, Windows Service, the Registry.

  6. 49 CFR 230.89 - Reverse gear.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Reverse gear. 230.89 Section 230.89 Transportation... Reversing Gear § 230.89 Reverse gear. (a) General provisions. Reverse gear, reverse levers, and quadrants... quadrant. Proper counterbalance shall be provided for the valve gear. (b) Air-operated power reverse gear...

  7. Field reversal experiments (FRX)

    International Nuclear Information System (INIS)

    Linford, R.K.; Armstrong, W.T.; Platts, D.A.; Sherwood, E.G.

    1978-01-01

    The equilibrium, confinement, and stability properties of the reversed-field configuration (RFC) are being studied in two theta-pinch facilities. The RFC is an elongated toroidal plasma confined in a purely poloidal field geometry. The open field lines of the linear theta pinch support the closed-field RFC much like the vertical field centers the toroidal plasma in a tokamak. Depending on stability and confinement properties, the RFC might be used to greatly reduce the axial losses in linear fusion devices such as mirrors, theta pinches, and liners. The FRX systems produce RFC's with a major radius R = 2-6 cm, minor radius a approximately 2 cm, and a total length l approximately 35 cm. The observed temperatures are T/sub e/ approximately 100 eV and T/sub i/ = 150-350 eV with a peak density n approximately 2 x 10 15 cm -3 . After the plasma reaches equilibrium, the RFC remains stable for up to 30 μs followed by the rapid growth of the rotational m = 2 instability, which terminates the confinement. During the stable equilibrium, the particle and energy confinement times are more than 10 times longer than in an open-field system. The behavior of the m = 2 mode qualitatively agrees with the theoretically predicted instability for rotational velocities exceeding some critical value

  8. Field reversal experiments (FRX)

    International Nuclear Information System (INIS)

    Linford, R.K.; Armstrong, W.T.; Platts, D.A.; Sherwood, E.G.

    1979-01-01

    The equilibrium, confinement, and stability properties of the reversed-field configuration (RFC) are being studied in two theta-pinch facilities. The RFC is an elongated toroidal plasma confined in a purely poloidal field geometry. The open field lines of the linear theta pinch support the closed-field RFC much like the vertical field centres the toroidal plasma in a tokamak. Depending on stability and confinement properties, the RFC might be used to greatly reduce the axial losses in linear fusion devices such as mirrors, theta pinches, and liners. The FRX systems produce RFCs with a major radius R=2-6cm, a minor radius a approximately 2cm, and a total length l approximately 35cm. The observed temperatures are Tsub(e) approximately 100eV and Tsub(i)=150-350eV with a peak density n approximately 2x10 15 cm -3 . After the plasma has reached equilibrium, the RFC remains stable for up to 30μs, followed by the rapid growth of the rotational m=2 instability, which terminates the confinement. During the stable equilibrium, the particle and energy confinement times are more than 10 times longer than in an open-field system. The behaviour of the m=2 mode agrees qualitatively with the theoretically predicted instability for rotational velocities exceeding some critical value. (author)

  9. Plasticity of hippocampal stem/progenitor cells to enhance neurogenesis in response to kainate-induced injury is lost by middle age

    OpenAIRE

    Hattiangady, Bharathi; Rao, Muddanna S.; Shetty, Ashok K.

    2008-01-01

    A remarkable up-regulation of neurogenesis through increased proliferation of neural stem/progenitor cells (NSCs) is a well-known plasticity displayed by the young dentate gyrus (DG) following brain injury. To ascertain whether this plasticity is preserved during aging, we quantified DG neurogenesis in the young adult, middle-aged and aged F344 rats after kainic acid induced hippocampal injury. Measurement of new cells that are added to the dentate granule cell layer (GCL) between post-injury...

  10. Acute alterations of somatodendritic action potential dynamics in hippocampal CA1 pyramidal cells after kainate-induced status epilepticus in mice.

    Directory of Open Access Journals (Sweden)

    Daniel Minge

    Full Text Available Pathophysiological remodeling processes at an early stage of an acquired epilepsy are critical but not well understood. Therefore, we examined acute changes in action potential (AP dynamics immediately following status epilepticus (SE in mice. SE was induced by intraperitoneal (i.p. injection of kainate, and behavioral manifestation of SE was monitored for 3-4 h. After this time interval CA1 pyramidal cells were studied ex vivo with whole-cell current-clamp and Ca(2+ imaging techniques in a hippocampal slice preparation. Following acute SE both resting potential and firing threshold were modestly depolarized (2-5 mV. No changes were seen in input resistance or membrane time constant, but AP latency was prolonged and AP upstroke velocity reduced following acute SE. All cells showed an increase in AP halfwidth and regular (rather than burst firing, and in a fraction of cells the notch, typically preceding spike afterdepolarization (ADP, was absent following acute SE. Notably, the typical attenuation of backpropagating action potential (b-AP-induced Ca(2+ signals along the apical dendrite was strengthened following acute SE. The effects of acute SE on the retrograde spread of excitation were mimicked by applying the Kv4 current potentiating drug NS5806. Our data unveil a reduced somatodendritic excitability in hippocampal CA1 pyramidal cells immediately after acute SE with a possible involvement of both Na(+ and K(+ current components.

  11. Towards a reversible functional language

    DEFF Research Database (Denmark)

    Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

    2012-01-01

    /equality operator also simplifies inverse computation and program inversion. We discuss the advantages of a reversible functional language using example programs, including run-length encoding. Program inversion is seen to be as lightweight as for imperative reversible languages and realized by recursive descent...

  12. Reverse engineering of RFID devices

    NARCIS (Netherlands)

    Bokslag, W.

    2015-01-01

    This paper discusses the relevance and potential impact of both RFID and reverse engineering of RFID technology, followed by a discussion of common protocols and internals of RFID technology. The focus of the paper is on providing an overview of the different approaches to reverse engineering RFID

  13. How decision reversibility affects motivation

    NARCIS (Netherlands)

    Bullens, L.; van Harreveld, F.; Förster, J.; Higgins, T.E.

    2014-01-01

    The present research examined how decision reversibility can affect motivation. On the basis of extant findings, it was suggested that 1 way it could affect motivation would be to strengthen different regulatory foci, with reversible decision making, compared to irreversible decision making,

  14. Enzymatic reactions in reversed micelles

    NARCIS (Netherlands)

    Hilhorst, M.H.

    1984-01-01

    It has been recognised that enzymes in reversed micelles have potential for application in chemical synthesis. Before these expectations will be realised many problems must be overcome. This thesis deals with some of them.
    In Chapter 1 the present knowledge about reversed micelles and

  15. Reversible networks in supramolecular polymers

    NARCIS (Netherlands)

    Havermans - van Beek, D.J.M.

    2007-01-01

    Non–covalent interactions between low molecular weight polymers form the basis of supramolecular polymers. The material properties of such polymers are determined by the strength and lifetime of the non–covalent reversible interactions. Due to the reversibility of the interactions between the low

  16. Reverse genetics of avian metapneumoviruses

    Science.gov (United States)

    An overview of avian metapneumovirus (aMPV) infection in turkeys and development of a reverse genetics system for aMPV subgroup C (aMPV-C) virus will be presented. By using reverse genetics technology, we generated recombinant aMPV-C viruses containing a different length of glycoprotein (G) gene or...

  17. MODELS OF PROJECT REVERSE ENGINEERING

    Directory of Open Access Journals (Sweden)

    Віктор Володимирович ІВАНОВ

    2017-03-01

    Full Text Available Reverse engineering decided important scientific and technical problems of increasing the cost of the existing technical product by transforming it into a product with other features or design. Search ideas of the new application of existing products on the base of heuristic analysis were created. The concept of reverse engineering and its division into three types: conceptual, aggregate and complete was expanded. The use of heuristic methods for reverse engineering concept was showed. The modification model of Reverse engineering based on the model of РМВОК was developed. Our model includes two new phases: identification and transformation. At the identification phase, technical control is made. At the transformation phase, search heuristic idea of the new applied existing technical product was made. The model of execution phase that included heuristic methods, metrological equipment, and CAD/CAM/CAE program complex was created. The model that connected economic indicators of reverse engineering project was developed.

  18. What do reversible programs compute?

    DEFF Research Database (Denmark)

    Axelsen, Holger Bock; Glück, Robert

    2011-01-01

    Reversible computing is the study of computation models that exhibit both forward and backward determinism. Understanding the fundamental properties of such models is not only relevant for reversible programming, but has also been found important in other fields, e.g., bidirectional model...... transformation, program transformations such as inversion, and general static prediction of program properties. Historically, work on reversible computing has focussed on reversible simulations of irreversible computations. Here, we take the viewpoint that the property of reversibility itself should...... are not strictly classically universal, but that they support another notion of universality; we call this RTM-universality. Thus, even though the RTMs are sub-universal in the classical sense, they are powerful enough as to include a self-interpreter. Lifting this to other computation models, we propose r...

  19. Fundamentals of reversible flowchart languages

    DEFF Research Database (Denmark)

    Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

    2016-01-01

    Abstract This paper presents the fundamentals of reversible flowcharts. They are intended to naturally represent the structure and control flow of reversible (imperative) programming languages in a simple computation model, in the same way classical flowcharts do for conventional languages......, structured reversible flowcharts are as expressive as unstructured ones, as shown by a reversible version of the classic Structured Program Theorem. We illustrate how reversible flowcharts can be concretized with two example programming languages, complete with syntax and semantics: a low-level unstructured...... language and a high-level structured language. We introduce concrete tools such as program inverters and translators for both languages, which follow the structure suggested by the flowchart model. To further illustrate the different concepts and tools brought together in this paper, we present two major...

  20. Time reversal technique for gas leakage detection.

    Science.gov (United States)

    Maksimov, A O; Polovinka, Yu A

    2015-04-01

    The acoustic remote sensing of subsea gas leakage traditionally uses sonars as active acoustic sensors and hydrophones picking up the sound generated by a leak as passive sensors. When gas leaks occur underwater, bubbles are produced and emit sound at frequencies intimately related to their sizes. The experimental implementation of an acoustic time-reversal mirror (TRM) is now well established in underwater acoustics. In the basic TRM experiment, a probe source emits a pulse that is received on an array of sensors, time reversed, and re-emitted. After time reversal, the resulting field focuses back at the probe position. In this study, a method for enhancing operation of the passive receiving system has been proposed by using it in the regime of TRM. Two factors, the local character of the acoustic emission signal caused by the leakage and a resonant nature of the bubble radiation at their birth, make particularly effective scattering with the conjugate wave (CW). Analytical calculations are performed for the scattering of CW wave on a single bubble when CW is formed by bubble birthing wail received on an array, time reversed, and re-emitted. The quality of leakage detection depends on the spatio-temporal distribution of ambient noise.

  1. The Geomagnetic Field During a Reversal

    Science.gov (United States)

    Heirtzler, James R.

    2003-01-01

    By modifying the IGRF it is possible to learn what may happen to the geomagnetic field during a geomagnetic reversal. If the entire IGRF reverses then the declination and inclination only reverse when the field strength is zero. If only the dipole component of the IGRF reverses a large geomagnetic field remains when the dipole component is zero and he direction of the field at the end of the reversal is not exactly reversed from the directions at the beginning of the reversal.

  2. Speciation of As(III) and As(V) in water and sediment using reverse-phase ion-pair high-performance liquid chromatography-neutron activation analysis (HPLC-NAA).

    Science.gov (United States)

    Tulasi, Delali; Adotey, Dennis; Affum, Andrews; Carboo, Derick; Serfor-Armah, Yaw

    2013-10-01

    Total As content and the As species distribution in water and sediments from the Kwabrafo stream, a major water body draining the Obuasi gold mining community in southwestern Ghana, have been investigated. Total As content was determined by instrumental neutron activation analysis (INAA). Ion-pair reverse phase high-performance liquid chromatography-neutron activation analysis (HPLC-NAA) was used for speciation of As species. Solid phase extraction with phosphate buffer was used to extract soluble As species from lyophilized sediment. The mass balance after phosphate extraction of soluble As species in sediment varied from 89 to 96 %. Compositionally appropriate reference material International Atomic Energy Agency (IAEA)-Lake Sediment (SL)-1 was used to check the validity of INAA method for total As determination. The measured values are in good agreement with the IAEA recommended value and also within the 95 % confidence interval. The accuracy of the measurement in terms of relative deviation from the IAEA recommended value was ±0.83 %. "In-house" prepared As(III) and As(V) standards were used to validate the HPLC-INAA method used for the As species determination. Total As concentration in the water samples ranged from 1.15 to 9.20 mg/L. As(III) species in water varied from 0.13 to 0.7 mg/L, while As(V) species varied from 0.79 to 3.85 mg/L. Total As content in sediment ranged from 2,134 to 3,596 mg/kg dry mass. The levels of As(III) and As(V) species in the sediment ranges from 138 to 506 mg/kg dry mass and 156 to 385 mg/kg dry mass, respectively.

  3. How decision reversibility affects motivation.

    Science.gov (United States)

    Bullens, Lottie; van Harreveld, Frenk; Förster, Jens; Higgins, Tory E

    2014-04-01

    The present research examined how decision reversibility can affect motivation. On the basis of extant findings, it was suggested that 1 way it could affect motivation would be to strengthen different regulatory foci, with reversible decision making, compared to irreversible decision making, strengthening prevention-related motivation relatively more than promotion-related motivation. If so, then decision reversibility should have effects associated with the relative differences between prevention and promotion motivation. In 5 studies, we manipulated the reversibility of a decision and used different indicators of regulatory focus motivation to test these predictions. Specifically, Study 1 tested for differences in participants' preference for approach versus avoidance strategies toward a desired end state. In Study 2, we used speed and accuracy performance as indicators of participants' regulatory motivation, and in Study 3, we measured global versus local reaction time performance. In Study 4, we approached the research question in a different way, making use of the value-from-fit hypothesis (Higgins, 2000, 2002). We tested whether a fit between chronic regulatory focus and focus induced by the reversibility of the decision increased participants' subjective positive feelings about the decision outcome. Finally, in Study 5, we tested whether regulatory motivation, induced by decision reversibility, also influenced participants' preference in specific product features. The results generally support our hypothesis showing that, compared to irreversible decisions, reversible decisions strengthen a prevention focus more than a promotion focus. Implications for research on decision making are discussed.

  4. Supercritical fluid reverse micelle separation

    Science.gov (United States)

    Fulton, J.L.; Smith, R.D.

    1993-11-30

    A method of separating solute material from a polar fluid in a first polar fluid phase is provided. The method comprises combining a polar fluid, a second fluid that is a gas at standard temperature and pressure and has a critical density, and a surfactant. The solute material is dissolved in the polar fluid to define the first polar fluid phase. The combined polar and second fluids, surfactant, and solute material dissolved in the polar fluid is maintained under near critical or supercritical temperature and pressure conditions such that the density of the second fluid exceeds the critical density thereof. In this way, a reverse micelle system defining a reverse micelle solvent is formed which comprises a continuous phase in the second fluid and a plurality of reverse micelles dispersed in the continuous phase. The solute material is dissolved in the polar fluid and is in chemical equilibrium with the reverse micelles. The first polar fluid phase and the continuous phase are immiscible. The reverse micelles each comprise a dynamic aggregate of surfactant molecules surrounding a core of the polar fluid. The reverse micelle solvent has a polar fluid-to-surfactant molar ratio W, which can vary over a range having a maximum ratio W[sub o] that determines the maximum size of the reverse micelles. The maximum ratio W[sub o] of the reverse micelle solvent is then varied, and the solute material from the first polar fluid phase is transported into the reverse micelles in the continuous phase at an extraction efficiency determined by the critical or supercritical conditions. 27 figures.

  5. Reverse engineering for quality systems

    International Nuclear Information System (INIS)

    Nolan, A.J.

    1995-01-01

    When the age of software engineering began, many companies were faced with a problem of how to support the older, pre-software-engineering, programs. The techniques of reverse engineering and re-engineering were developed to bridge the gap between the past and the present. Although reverse engineering can be used for generating missing documentation, it can also be used as a means to demonstrate quality in these older programs. This paper presents, in the form of a case study, how Rolls-Royce and Associates Limited addressed the quality issues of reverse engineering and re-engineering. (author)

  6. Field reversal in mirror machines

    International Nuclear Information System (INIS)

    Pearlstein, L.D.; Anderson, D.V.; Boozer, A.H.

    1978-01-01

    This report discusses some of the physics issues anticipated in field-reversed mirrors. The effect of current cancellation due to electrons is described. An estimate is made of the required impurity level to maintain a field-reversed configuration. The SUPERLAYER code is used to simulate the high-β 2XIIB results, and favorable comparisons require inclusion of quasilinear RF turbulence. Impact of a quadrupole field on field-line closure and resonant transport is discussed. A simple self-consistent model of ion currents is presented. Conditions for stability of field-reversed configurations to E x B driven rotations are determined

  7. Dynamical similarity of geomagnetic field reversals.

    Science.gov (United States)

    Valet, Jean-Pierre; Fournier, Alexandre; Courtillot, Vincent; Herrero-Bervera, Emilio

    2012-10-04

    No consensus has been reached so far on the properties of the geomagnetic field during reversals or on the main features that might reveal its dynamics. A main characteristic of the reversing field is a large decrease in the axial dipole and the dominant role of non-dipole components. Other features strongly depend on whether they are derived from sedimentary or volcanic records. Only thermal remanent magnetization of lava flows can capture faithful records of a rapidly varying non-dipole field, but, because of episodic volcanic activity, sequences of overlying flows yield incomplete records. Here we show that the ten most detailed volcanic records of reversals can be matched in a very satisfactory way, under the assumption of a common duration, revealing common dynamical characteristics. We infer that the reversal process has remained unchanged, with the same time constants and durations, at least since 180 million years ago. We propose that the reversing field is characterized by three successive phases: a precursory event, a 180° polarity switch and a rebound. The first and third phases reflect the emergence of the non-dipole field with large-amplitude secular variation. They are rarely both recorded at the same site owing to the rapidly changing field geometry and last for less than 2,500 years. The actual transit between the two polarities does not last longer than 1,000 years and might therefore result from mechanisms other than those governing normal secular variation. Such changes are too brief to be accurately recorded by most sediments.

  8. Zero field reversal probability in thermally assisted magnetization reversal

    Science.gov (United States)

    Prasetya, E. B.; Utari; Purnama, B.

    2017-11-01

    This paper discussed about zero field reversal probability in thermally assisted magnetization reversal (TAMR). Appearance of reversal probability in zero field investigated through micromagnetic simulation by solving stochastic Landau-Lifshitz-Gibert (LLG). The perpendicularly anisotropy magnetic dot of 50×50×20 nm3 is considered as single cell magnetic storage of magnetic random acces memory (MRAM). Thermally assisted magnetization reversal was performed by cooling writing process from near/almost Curie point to room temperature on 20 times runs for different randomly magnetized state. The results show that the probability reversal under zero magnetic field decreased with the increase of the energy barrier. The zero-field probability switching of 55% attained for energy barrier of 60 k B T and the reversal probability become zero noted at energy barrier of 2348 k B T. The higest zero-field switching probability of 55% attained for energy barrier of 60 k B T which corespond to magnetif field of 150 Oe for switching.

  9. A Typology of Reverse Innovation

    DEFF Research Database (Denmark)

    von Zedtwitz, Max; Corsi, Simone; Søberg, Peder Veng

    2015-01-01

    secondary market introduction, this study expands the espoused definition of reverse innovation beyond its market-introduction focus with reversals in the flow of innovation in the ideation and product development phases. Recognizing that each phase can take place in different geographical locations...... taking place in an emerging country. This analytical framework allows recasting of current research at the intersection between innovation and international business. Of the 10 reverse innovation flows, six are new and have not been covered in the literature to date. The study addresses questions......’s portfolio of global innovation competence and capability. The implications for management are concerned with internal and external resistance to reverse innovation. Most significantly, while greater recognition and power of innovation in formerly subordinate organizational units is inconvenient to some...

  10. Reversal of multidrug resistance by surfactants.

    Science.gov (United States)

    Woodcock, D. M.; Linsenmeyer, M. E.; Chojnowski, G.; Kriegler, A. B.; Nink, V.; Webster, L. K.; Sawyer, W. H.

    1992-01-01

    Cremophor EL, a pharmacologically inactive solubilising agent, has been shown to reverse multidrug resistance (MDR). Using flow cytometric evaluation of equilibrium intracellular levels of daunorubicin (DNR), we found that eight other surface active agents will also reverse MDR. All the active detergents contain polyethoxylated moieties but have no similarities in their hydrophobic components. The properties of three polyethoxylated surfactants that showed the lowest toxicities, Cremophor, Tween 80 and Solutol HS15, were examined in more detail. The concentrations of Tween 80 and Solutol required to reverse DNR exclusion were 10-fold lower than for Cremophor. However while concentrations greater than or equal to 1:10(2) of the former two surfactants resulted in breakdown of cells, even 1:10 of Cremophor did not lyse cells. Studies of the effects of Cremophor on the uptake and efflux of DNR in normal and MDR cell types showed that Cremophor increases intracellular DNR primarily by locking the rapid efflux from the cells. This blockage of drug efflux may be mediated by a substantial alteration in the fluidity of cell membranes induced by Cremophor, as shown by decreased fluorescence anisotropy of a membrane probe. Consistent with these data, coinjection of adriamycin plus Cremophor into mice carrying a multidrug resistant P388 transplantable tumour significantly increased the survival time of the mice compared with adriamycin treatment alone. PMID:1637678

  11. Comparing Effectiveness of Active and Passive Client Follow-Up Approaches in Sustaining the Continued Use of Long Acting Reversible Contraceptives (LARC) in Rural Punjab: A Multicentre, Non-Inferiority Trial

    Science.gov (United States)

    Hameed, Waqas; Azmat, Syed Khurram; Ali, Moazzam; Ishaque, Muhammad; Abbas, Ghazunfer; Munroe, Erik; Harrison, Rebecca; Shamsi, Wajahat Hussain; Mustafa, Ghulam; Khan, Omar Farooq; Ali, Safdar; Ahmed, Aftab

    2016-01-01

    Background The use of long-acting reversible contraceptive (LARC) methods is very low in Pakistan with high discontinuation rates mainly attributed to method-related side effects. Mixed evidence is available on the effectiveness of different client follow-up approaches used to ensure method continuation. We compared the effectiveness of active and passive follow-up approaches in sustaining the use of LARC—and within ‘active’ follow-up, we further compared a telephone versus home-based approach in rural Punjab, Pakistan. Methods This was a 12-month multicentre non-inferiority trial conducted in twenty-two (16 rural- and 6 urban-based) franchised reproductive healthcare facilities in district Chakwal of Punjab province, between November 2013 and December 2014. The study comprised of three groups of LARC clients: a) home-based follow-up, b) telephone-based follow-up, and c) passive or needs-based follow-up. Participants in the first two study groups received counselling on scheduled follow-up from the field workers at 1, 3, 6, 9, and 12 month post-insertion whereas participants in the third group were asked to contact the health facility if in need of medical assistance relating to LARC method use. Study participants were recruited with equal allocation to each study group, but participants were not randomized. The analyses are based on 1,246 LARC (intra-uterine contraceptive device and implant) users that completed approximately 12-months of follow-up. The non-inferiority margin was kept at five percentage points for the comparison of active and passive follow-up and six percentage points for telephone and home-based approach. The primary outcome was cumulative probability of method continuation at 12-month among LARC users. Results Women recruited in home-based, telephone-based, and passive groups were 400, 419 and 427, respectively. The cumulative probability of LARC continuation at 12 month was 87.6% (95% CI 83.8 to 90.6) among women who received home

  12. Silencing of reversion-inducing cysteine-rich protein with Kazal motifs stimulates hyperplastic phenotypes through activation of epidermal growth factor receptor and hypoxia-inducible factor-2α.

    Directory of Open Access Journals (Sweden)

    You Mie Lee

    Full Text Available Reversion-inducing cysteine-rich protein with Kazal motifs (RECK, a tumor suppressor is down-regulated by the oncogenic signals and hypoxia, but the biological function of RECK in early tumorigenic hyperplastic phenotypes is largely unknown. Knockdown of RECK by small interfering RNA (siRECK or hypoxia significantly promoted cell proliferation in various normal epithelial cells. Hypoxia as well as knockdown of RECK by siRNA increased the cell cycle progression, the levels of cyclin D1 and c-Myc, and the phosphorylation of Rb protein (p-pRb, but decreased the expression of p21(cip1, p27(kip1, and p16(ink4A. HIF-2α was upregulated by knockdown of RECK, indicating HIF-2α is a downstream target of RECK. As knockdown of RECK induced the activation of epidermal growth factor receptor (EGFR and treatment of an EGFR kinase inhibitor, gefitinib, suppressed HIF-2α expression induced by the silencing of RECK, we can suggest that the RECK silenicng-EGFR-HIF-2α axis might be a key molecular mechanism to induce hyperplastic phenotype of epithelial cells. It was also found that shRNA of RECK induced larger and more numerous colonies than control cells in an anchorage-independent colony formation assay. Using a xenograft assay, epithelial cells with stably transfected with shRNA of RECK formed a solid mass earlier and larger than those with control cells in nude mice. In conclusion, the suppression of RECK may promote the development of early tumorigenic hyperplastic characteristics in hypoxic stress.

  13. Activities of the human immunodeficiency virus type 1 (HIV-1) protease inhibitor nelfinavir mesylate in combination with reverse transcriptase and protease inhibitors against acute HIV-1 infection in vitro.

    Science.gov (United States)

    Patick, A K; Boritzki, T J; Bloom, L A

    1997-10-01

    Nelfinavir mesylate (formerly AG1343) is a potent and selective, nonpeptidic inhibitor of human immunodeficiency virus type 1 (HIV-1) protease that was discovered by protein structure-based design methodologies. We evaluated the antiviral and cytotoxic effects of two-drug combinations of nelfinavir with the clinically approved antiretroviral therapeutics zidovudine (ZDV), lamivudine (3TC), dideoxycytidine (ddC; zalcitabine), stavudine (d4T), didanosine (ddI), indinavir, saquinavir, and ritonavir and a three-drug combination of nelfinavir with ZDV and 3TC against an acute HIV-1 strain RF infection of CEM-SS cells in vitro. Quantitative assessment of drug interaction was evaluated by a universal response surface approach (W. R. Greco, G. Bravo, and J. C. Parsons, Pharm. Rev. 47:331-385, 1995) and by the method of M. N. Prichard and C. Shipman (Antiviral Res. 14:181-206, 1990). Both analytical methods yielded similar results and showed that the two-drug combinations of nelfinavir with the reverse transcriptase inhibitors ZDV, 3TC, ddI, d4T, and ddC and the three-drug combination with ZDV and 3TC resulted in additive to statistically significant synergistic interactions. In a similar manner, the combination of nelfinavir with the three protease inhibitors resulted in additive (ritonavir and saquinavir) to slightly antagonistic (indinavir) interactions. In all combinations, minimal cellular cytotoxicity was observed with any drug alone and in combination. These results suggest that administration of combinations of the appropriate doses of nelfinavir with other currently approved antiretroviral therapeutic agents in vivo may result in enhanced antiviral activity with no associated increase in cellular cytotoxicity.

  14. Spontaneous direct and reverse osmosis

    International Nuclear Information System (INIS)

    Valitov, N.Kh.

    1996-01-01

    It has been ascertained experimentally that in the course of separation of CsCl, KCl, NaCl aqueous solutions by semi-permeable membrane from distilled water the direct and then reverse osmosis are observed. The same sequence is observed in case of separation of CsCl aqueous solutions from NaCl of different concentrations. The reason for the direct and reverse osmosis has been explained. 5 refs.; 3 figs. 1 tab

  15. Garbage collection for reversible functional languages

    DEFF Research Database (Denmark)

    Mogensen, Torben Ægidius

    2015-01-01

    Reversible languages are programming languages where all programs can run both forwards and backwards. Reversible functional languages have been proposed that use symmetric pattern matching and data construction. To be reversible, these languages require linearity: Every variable must be used...

  16. Removal of radionuclides in drinking water by membrane treatment using ultrafiltration, reverse osmosis and electrodialysis reversal

    International Nuclear Information System (INIS)

    Montaña, M.; Camacho, A.; Serrano, I.; Devesa, R.; Matia, L.; Vallés, I.

    2013-01-01

    A pilot plant had been built to test the behaviour of ultrafiltration (UF), reverse osmosis (RO), and electrodialysis reversal (EDR) in order to improve the quality of the water supplied to Barcelona metropolitan area from the Llobregat River. This paper presents results from two studies to reduce natural radioactivity. The results from the pilot plant with four different scenarios were used to design the full-scale treatment plant built (SJD WTP). The samples taken at different steps of the treatment were analysed to determine gross alpha, gross beta and uranium activity. The results obtained revealed a significant improvement in the radiological water quality provided by both membrane techniques (RO and EDR showed removal rates higher than 60%). However, UF did not show any significant removal capacity for gross alpha, gross beta or uranium activities. RO was better at reducing the radiological parameters studied and this treatment was selected and applied at the full scale treatment plant. The RO treatment used at the SJD WTP reduced the concentration of both gross alpha and gross beta activities and also produced water of high quality with an average removal of 95% for gross alpha activity and almost 93% for gross beta activity at the treatment plant. -- Highlights: ► A study with a pilot plant using different membranes technologies was made. ► Big reduction on natural uranium and 40 K by reverse osmosis was found. ► Pilot plant and full-scale treatment plant behave similarly

  17. The treatment of radioactive aqueous wastes by reverse osmosis

    International Nuclear Information System (INIS)

    Hodgson, T.D.

    Experiments were carried out to determine the rejection factors for the more important radionuclides found in aqueous wastes, to study activity deposition within reverse osmosis modules, and to obtain experience in active operation of a reverse osmosis facility. It was found that reverse osmosis is likely to be useful in aqueous radioactive waste treatment when a wide range of contaminants rather than a specific radioactive species must be removed. There appeared to be no barrier to active operation, although greater confidence in the reliability of pumps and membranes is needed. The rejection of trace quantities of radioisotopes such as Cs + or Sr ++ could be predicted from the behaviour of similar inactive ions. Activity present as polyvalent ions or colloidal aggregates is highly rejected by the membrane. Activity may be deposited onto the membrane with insoluble or scaling compounds, and is greatest on areas of the membrane shielded from the sweeping action of the liquor flow

  18. Contribution of the reverse endoprosthesis to glenohumeral kinematics.

    OpenAIRE

    Bergmann, J.H.M.; de Leeuw, M.; Janssen, T.W.J.; Veeger, H.E.J.; Willems, W.J.

    2008-01-01

    After placement of a reverse shoulder endoprosthesis, range of motion is usually still compromised. To what extent this occurs from limitation in motion of the reverse endoprosthesis is, however, unclear. We measured the motion pattern of 16 patients (18 shoulders) during three active and passive range of motion tasks using a six degree-of-freedom electromagnetic tracking device. Despite rotator cuff deficiencies, glenohumeral elevation contributed roughly two-thirds of the total thoracohumer...

  19. Vasectomy reversal: a clinical update

    Directory of Open Access Journals (Sweden)

    Abhishek P Patel

    2016-01-01

    Full Text Available Vasectomy is a safe and effective method of contraception used by 42-60 million men worldwide. Approximately 3%-6% of men opt for a vasectomy reversal due to the death of a child or divorce and remarriage, change in financial situation, desire for more children within the same marriage, or to alleviate the dreaded postvasectomy pain syndrome. Unlike vasectomy, vasectomy reversal is a much more technically challenging procedure that is performed only by a minority of urologists and places a larger financial strain on the patient since it is usually not covered by insurance. Interest in this procedure has increased since the operating microscope became available in the 1970s, which consequently led to improved patency and pregnancy rates following the procedure. In this clinical update, we discuss patient evaluation, variables that may influence reversal success rates, factors to consider in choosing to perform vasovasostomy versus vasoepididymostomy, and the usefulness of vasectomy reversal to alleviate postvasectomy pain syndrome. We also review the use of robotics for vasectomy reversal and other novel techniques and instrumentation that have emerged in recent years to aid in the success of this surgery.

  20. Magnetization reversal in single molecule magnets

    Science.gov (United States)

    Bokacheva, Louisa

    2002-09-01

    I have studied the magnetization reversal in single molecule magnets (SMMs). SMMs are Van der Waals crystals, consisting of identical molecules containing transition metal ions, with high spin and large uniaxial magnetic anisotropy. They can be considered as ensembles of identical, iso-oriented nanomagnets. At high temperature, these materials behave as superparamagnets and their magnetization reversal occurs by thermal activation. At low temperature they become blocked, and their magnetic relaxation occurs via thermally assisted tunneling or pure quantum tunneling through the anisotropy barrier. We have conducted detailed experimental studies of the magnetization reversal in SMM material Mn12-acetate (Mn12) with S = 10. Low temperature measurements were conducted using micro-Hall effect magnetometry. We performed hysteresis and relaxation studies as a function of temperature, transverse field, and magnetization state of the sample. We identified magnetic sublevels that dominate the tunneling at a given field, temperature and magnetization. We observed a crossover between thermally assisted and pure quantum tunneling. The form of this crossover depends on the magnitude and direction of the applied field. This crossover is abrupt (first-order) and occurs in a narrow temperature interval (tunneling mechanisms in Mn12.

  1. Reverse Knowledge Transfer in MNEs

    DEFF Research Database (Denmark)

    Mudambi, Ram; Piscitello, Lucia; Rabbiosi, Larissa

    2014-01-01

    a positive correlation with the extent of reverse knowledge transfers to the parent MNE. Relying on the headquarters-subsidiary view of the MNE, we argue that, beyond a point, increasing subsidiary innovativeness will be associated with lower reverse knowledge transfers. Further, we argue......It is now well recognized that multinational enterprises (MNEs) are differentiated networks wherein subsidiaries vary in terms of their ability to create new knowledge and competencies for their parent groups. In much of this theory, it is taken for granted that subsidiary innovativeness has...... that this relationship is sensitive to the subsidiary entry mode. Using data from a sample of 293 Italian subsidiaries, we find strong support for our hypotheses. In particular, our results confirm that the effect of subsidiary innovativeness on reverse knowledge transfers displays an inverted-U shape...

  2. Ice ages and geomagnetic reversals

    Science.gov (United States)

    Wu, Patrick

    1992-01-01

    There have been speculations on the relationship between climatic cooling and polarity reversals of the earth's magnetic field during the Pleistocene. Two of the common criticisms on this relationship have been the reality of these short duration geomagnetic events and the accuracy of their dates. Champion et al. (1988) have reviewed recent progress in this area. They identified a total of 10 short-duration polarity events in the last 1 Ma and 6 of these events have been found in volcanic rocks, which also have K-Ar dates. Supposing that the speculated relationship between climatic cooling and geomagnetic reversals actually exist, two mechanisms that assume climatic cooling causes short period magnetic reversals will be investigated. These two methods are core-mantle boundary topography and transfer of the rotational energy to the core.

  3. Reverse innovation in maternal health.

    Science.gov (United States)

    Firoz, Tabassum; Makanga, Prestige Tatenda; Nathan, Hannah L; Payne, Beth; Magee, Laura A

    2017-09-01

    Reverse innovation, defined as the flow of ideas from low- to high-income settings, is gaining traction in healthcare. With an increasing focus on value, investing in low-cost but effective and innovative solutions can be of mutual benefit to both high- and low-income countries. Reverse innovation has a role in addressing maternal health challenges in high-income countries by harnessing these innovative solutions for vulnerable populations especially in rural and remote regions. In this paper, we present three examples of 'reverse innovation' for maternal health: a low-cost, easy-to-use blood pressure device (CRADLE), a diagnostic algorithm (mini PIERS) and accompanying mobile app (PIERS on the Move), and a novel method for mapping maternal outcomes (MOM).

  4. Reverse Transfection Using Gold Nanoparticles

    Science.gov (United States)

    Yamada, Shigeru; Fujita, Satoshi; Uchimura, Eiichiro; Miyake, Masato; Miyake, Jun

    Reverse transfection from a solid surface has the potential to deliver genes into various types of cell and tissue more effectively than conventional methods of transfection. We present a method for reverse transfection using a gold colloid (GC) as a nanoscaffold by generating nanoclusters of the DNA/reagentcomplex on a glass surface, which could then be used for the regulation of the particle size of the complex and delivery of DNA into nuclei. With this method, we have found that the conjugation of gold nanoparticles (20 nm in particle size) to the pEGFP-N1/Jet-PEI complex resulted in an increase in the intensity of fluorescence of enhanced green fluorescent protein (EGFP) (based on the efficiency of transfection) from human mesenchymal stem cells (hMSCs), as compared with the control without GC. In this manner, we constructed a method for reverse transfection using GC to deliver genes into the cells effectively.

  5. Designing the Reverse Supply Chain

    DEFF Research Database (Denmark)

    Gobbi, Chiara

    2011-01-01

    Purpose – The purpose of this paper is to explore the impact of the product residual value (PRV) and the loss of value over time of returned products in the reverse supply chain configuration. It also examines whether or not the distinction of Fisher's functional and innovative products holds...... that allows for recapturing most of the PRV. These notions have then been tested by analyzing two reverse supply chains with a case study research methodology. Findings – The findings show that low PRV is associated with second-class recovery options (recycling and energy recovery) and that high PRV...... is associated with first-class recovery options (reconditioning and remarketing). When the recovery option is recycling, time is not relevant, the primary objective is cost reduction (efficiency), the chain is centralized, and actors and phases of the reverse chain are determined by the specificity...

  6. A model for 'reverse innovation' in health care.

    Science.gov (United States)

    Depasse, Jacqueline W; Lee, Patrick T

    2013-08-30

    'Reverse innovation,' a principle well established in the business world, describes the flow of ideas from emerging to more developed economies. There is strong and growing interest in applying this concept to health care, yet there is currently no framework for describing the stages of reverse innovation or identifying opportunities to accelerate the development process. This paper combines the business concept of reverse innovation with diffusion of innovation theory to propose a model for reverse innovation as a way to innovate in health care. Our model includes the following steps: (1) identifying a problem common to lower- and higher-income countries; (2) innovation and spread in the low-income country (LIC); (3) crossover to the higher-income country (HIC); and (4) innovation and spread in the HIC. The crucial populations in this pathway, drawing from diffusion of innovation theory, are LIC innovators, LIC early adopters, and HIC innovators. We illustrate the model with three examples of current reverse innovations. We then propose four sets of specific actions that forward-looking policymakers, entrepreneurs, health system leaders, and researchers may take to accelerate the movement of promising solutions through the reverse innovation pipeline: (1) identify high-priority problems shared by HICs and LICs; (2) create slack for change, especially for LIC innovators, LIC early adopters, and HIC innovators; (3) create spannable social distances between LIC early adopters and HIC innovators; and (4) measure reverse innovation activity globally.

  7. Computational reverse shoulder prosthesis model: Experimental data and verification.

    Science.gov (United States)

    Martins, A; Quental, C; Folgado, J; Ambrósio, J; Monteiro, J; Sarmento, M

    2015-09-18

    The reverse shoulder prosthesis aims to restore the stability and function of pathological shoulders, but the biomechanical aspects of the geometrical changes induced by the implant are yet to be fully understood. Considering a large-scale musculoskeletal model of the upper limb, the aim of this study is to evaluate how the Delta reverse shoulder prosthesis influences the biomechanical behavior of the shoulder joint. In this study, the kinematic data of an unloaded abduction in the frontal plane and an unloaded forward flexion in the sagittal plane were experimentally acquired through video-imaging for a control group, composed of 10 healthy shoulders, and a reverse shoulder group, composed of 3 reverse shoulders. Synchronously, the EMG data of 7 superficial muscles were also collected. The muscle force sharing problem was solved through the minimization of the metabolic energy consumption. The evaluation of the shoulder kinematics shows an increase in the lateral rotation of the scapula in the reverse shoulder group, and an increase in the contribution of the scapulothoracic joint to the shoulder joint. Regarding the muscle force sharing problem, the musculoskeletal model estimates an increased activity of the deltoid, teres minor, clavicular fibers of the pectoralis major, and coracobrachialis muscles in the reverse shoulder group. The comparison between the muscle forces predicted and the EMG data acquired revealed a good correlation, which provides further confidence in the model. Overall, the shoulder joint reaction force was lower in the reverse shoulder group than in the control group. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Reverse genetics with animal viruses. NSV reverse genetics

    International Nuclear Information System (INIS)

    Mebatsion, T.

    2005-01-01

    New strategies to genetically manipulate the genomes of several important animal pathogens have been established in recent years. This article focuses on the reverse genetics techniques, which enables genetic manipulation of the genomes of non-segmented negative-sense RNA viruses. Recovery of a negative-sense RNA virus entirely from cDNA was first achieved for rabies virus in 1994. Since then, reverse genetic systems have been established for several pathogens of medical and veterinary importance. Based on the reverse genetics technique, it is now possible to design safe and more effective live attenuated vaccines against important viral agents. In addition, genetically tagged recombinant viruses can be designed to facilitate serological differentiation of vaccinated animals from infected animals. The approach of delivering protective immunogens of different pathogens using a single vector was made possible with the introduction of the reverse genetics system, and these novel broad-spectrum vaccine vectors have potential applications in improving animal health in developing countries. (author)

  9. Marburg Virus Reverse Genetics Systems

    Directory of Open Access Journals (Sweden)

    Kristina Maria Schmidt

    2016-06-01

    Full Text Available The highly pathogenic Marburg virus (MARV is a member of the Filoviridae family and belongs to the group of nonsegmented negative-strand RNA viruses. Reverse genetics systems established for MARV have been used to study various aspects of the viral replication cycle, analyze host responses, image viral infection, and screen for antivirals. This article provides an overview of the currently established MARV reverse genetic systems based on minigenomes, infectious virus-like particles and full-length clones, and the research that has been conducted using these systems.

  10. Reverse hybrid total hip arthroplasty

    DEFF Research Database (Denmark)

    Wangen, Helge; Havelin, Leif I.; Fenstad, Anne M

    2017-01-01

    Background and purpose - The use of a cemented cup together with an uncemented stem in total hip arthroplasty (THA) has become popular in Norway and Sweden during the last decade. The results of this prosthetic concept, reverse hybrid THA, have been sparsely described. The Nordic Arthroplasty....... Patients and methods - From the NARA, we extracted data on reverse hybrid THAs from January 1, 2000 until December 31, 2013. 38,415 such hips were studied and compared with cemented THAs. The Kaplan-Meier method and Cox regression analyses were used to estimate the prosthesis survival and the relative risk...

  11. Reference counting for reversible languages

    DEFF Research Database (Denmark)

    Mogensen, Torben Ægidius

    2014-01-01

    inverses: Freeing a block of memory is done by running the allocation procedure backwards. Axelsen and Glück use this heap manager to sketch implementation of a simple reversible functional language where pattern matching a constructor is the inverse of construction, so pattern-matching implies......Modern programming languages and operating systems use heap memory that allows allocation and deallocation of memory to be decoupled, so they don't follow a stack discipline. Axelsen and Glück have presented a reversible heap manager where allocation and deallocation are each other's logical...

  12. Understanding Virtual Objects through Reverse Engineering

    Directory of Open Access Journals (Sweden)

    Vera Moitinho

    2012-11-01

    Full Text Available The main objective of our research is to develop a new methodology, based on Reverse Engineering processes – 3D scan, quantitative data analysis and Artificial Intelligence techniques, in particular simulation – to study the relationship between form and function of artefacts. Furthermore, we aim to provide new data, as well as possible explanations of the archaeological record according to what it expects about social activity, including working processes, by simulating the potentialities of such actions in terms of input-output relationships.

  13. Reverse triiodothyronine in protein energy malnutrition

    Energy Technology Data Exchange (ETDEWEB)

    Hafiez, A A; Abdel-Salam, E; Abbas, E Z; Halawa, F A; El-Hefnawy, N [Cairo Univ. (Egypt)

    1984-08-01

    Serum levels of thyroxine (T/sub 4/), triiodothyronine (T/sub 3/), reverse triiodothyronine (rT/sub 3/) and thyrotropin (TSH) were determined in cases of kwashiorkor and marasmus. Decreased levels of T/sub 4/ and T/sub 3/, and increased levels of rT/sub 3/ with no change in TSH were obtained. Thus in infants suffering from protein energy malnutrition there is a state of thyroid dysfunction as well as a shift in the peripheral T/sub 4/ metabolism being converted to the inert rT/sub 3/ rather than to the physiologically active T/sub 3/.

  14. Reverse triiodothyronine in protein energy malnutrition

    International Nuclear Information System (INIS)

    Hafiez, A.A.; Abdel-Salam, E.; Abbas, E.Z.; Halawa, F.A.; El-Hefnawy, N.

    1984-01-01

    Serum levels of thyroxine (T 4 ), triiodothyronine (T 3 ), reverse triiodothyronine (rT 3 ) and thyrotropin (TSH) were determined in cases of kwashiorkor and marasmus. Decreased levels of T 4 and T 3 , and increased levels of rT 3 with no change in TSH were obtained. Thus in infants suffering from protein energy malnutrition there is a state of thyroid dysfunction as well as a shift in the peripheral T 4 metabolism being converted to the inert rT 3 rather than to the physiologically active T 3 . (author)

  15. Dopamine D4 receptor activation increases hippocampal gamma oscillations by enhancing synchronization of fast-spiking interneurons.

    Directory of Open Access Journals (Sweden)

    Richard Andersson

    Full Text Available BACKGROUND: Gamma oscillations are electric activity patterns of the mammalian brain hypothesized to serve attention, sensory perception, working memory and memory encoding. They are disrupted or altered in schizophrenic patients with associated cognitive deficits, which persist in spite of treatment with antipsychotics. Because cognitive symptoms are a core feature of schizophrenia it is relevant to explore signaling pathways that potentially regulate gamma oscillations. Dopamine has been reported to decrease gamma oscillation power via D1-like receptors. Based on the expression pattern of D4 receptors (D4R in hippocampus, and pharmacological effects of D4R ligands in animals, we hypothesize that they are in a position to regulate gamma oscillations as well. METHODOLOGY/PRINCIPAL FINDINGS: To address this hypothesis we use rat hippocampal slices and kainate-induced gamma oscillations. Local field potential recordings as well as intracellular recordings of pyramidal cells, fast-spiking and non-fast-spiking interneurons were carried out. We show that D4R activation with the selective ligand PD168077 increases gamma oscillation power, which can be blocked by the D4R-specific antagonist L745,870 as well as by the antipsychotic drug Clozapine. Pyramidal cells did not exhibit changes in excitatory or inhibitory synaptic current amplitudes, but inhibitory currents became more coherent with the oscillations after application of PD168077. Fast-spiking, but not non-fast spiking, interneurons, increase their action potential phase-coupling and coherence with regard to ongoing gamma oscillations in response to D4R activation. Among several possible mechanisms we found that the NMDA receptor antagonist AP5 also blocks the D4R mediated increase in gamma oscillation power. CONCLUSIONS/SIGNIFICANCE: We conclude that D4R activation affects fast-spiking interneuron synchronization and thereby increases gamma power by an NMDA receptor-dependent mechanism. This

  16. A functional language for describing reversible logic

    DEFF Research Database (Denmark)

    Thomsen, Michael Kirkedal

    2012-01-01

    Reversible logic is a computational model where all gates are logically reversible and combined in circuits such that no values are lost or duplicated. This paper presents a novel functional language that is designed to describe only reversible logic circuits. The language includes high....... Reversibility of descriptions is guaranteed with a type system based on linear types. The language is applied to three examples of reversible computations (ALU, linear cosine transformation, and binary adder). The paper also outlines a design flow that ensures garbage- free translation to reversible logic...... circuits. The flow relies on a reversible combinator language as an intermediate language....

  17. Teach CAD and Measuring Skills through Reverse Engineering

    Science.gov (United States)

    Board, Keith

    2012-01-01

    This article describes a reverse engineering activity that gives students hands-on, minds-on experience with measuring tools, machine parts, and CAD. The author developed this activity to give students an abundance of practical experience with measuring tools. Equally important, it provides a good interface between the virtual world of CAD 3D…

  18. Reverse transcriptase-quantitative polymerase chain reaction (RT ...

    African Journals Online (AJOL)

    The reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) is a highly specific polymerase chain reaction (PCR) method that allows one to detect very low transcription levels of functional gene(s) in soil. RT-qPCR helps us to know the active members of the microbial community, and their activities can be ...

  19. Fiscal 1999 achievement report on regional consortium research and development project. Regional consortium activity in its 3rd year (Research and development of reverse engineering system for local craftwork articles); 1999 nendo chiiki kogeihin muke reverse engineering system no kenkyu kaihatsu seika hokokusho. 3

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-03-01

    The effort concerns Ryukyu craftwork articles. Reverse engineering used to be regarded as a technique of imitation or duplication but today it is drawing attention as a concept of positively utilizing the directionality of information flow in the integrated environment. In the development of a reverse information system, novel designs are created by utilizing a 3-dimensional data base, a high-efficiency fabrication technology for metal patterns for the press-molding of glass is established incorporating some fabrication diagnosing techniques, and a system is constructed under which fabrication accuracy is evaluated and difference data are fed back. In the development of technologies for metal pattern cutting and surface reforming, a metal pattern fabrication technology for molding glass, low in cost and high in performance, is systematized, which enables short delivery. In the diversification of glass products, Ryukyu patterns are collected and Ryukyu glass products are tentatively manufactured by press-molding, and a good result is achieved. In the field of total system technology, basic technologies for an advanced and integrated common production base are established. A virtual reality assisted designing system is developed, under which the designer feels force on the finger tips when preparing a shape for a 3-dimensional structure. (NEDO)

  20. Liquid-liquid extraction by reversed micelles in biotechnological processes

    Directory of Open Access Journals (Sweden)

    Kilikian B. V.

    2000-01-01

    Full Text Available In biotechnology there is a need for new purification and concentration processes for biologically active compounds such as proteins, enzymes, nucleic acids, or cells that combine a high selectivity and biocompatibility with an easy scale-up. A liquid-liquid extraction with a reversed micellar phase might serve these purposes owing to its capacity to solubilize specific biomolecules from dilute aqueous solutions such as fermentation and cell culture media. Reversed micelles are aggregates of surfactant molecules containing an inner core of water molecules, dispersed in a continuous organic solvent medium. These reversed micelles are capable of selectively solubilizing polar compounds in an apolar solvent. This review gives an overview of liquid-liquid extraction by reversed micelles for a better understanding of this process.

  1. CAPSULE REPORT: REVERSE OSMOSIS PROCESS

    Science.gov (United States)

    A failure analysis has been completed for the reverse osmosis (RO) process. The focus was on process failures that result in releases of liquids and vapors to the environment. The report includes the following: 1) A description of RO and coverage of the principles behind the proc...

  2. Time reversal and parity tests

    International Nuclear Information System (INIS)

    Terwilliger, K.

    1975-01-01

    A recent review by Henley discusses the present status of Time Reversal and Parity symmetry violations, and comments on the implications for high energy hadron scattering. This note will briefly summarize the situation with particular attention to the sizes of possible effects, relating them to experimental accuracy available or reasonably possible at the ZGS

  3. Reverse ventilation--perfusion mismatch

    International Nuclear Information System (INIS)

    Palmaz, J.C.; Barnett, C.A.; Reich, S.B.; Krumpe, P.E.; Farrer, P.A.

    1984-01-01

    Patients having lobar airway obstruction or consolidation usually have decreases of both ventilation and perfusion on lung scans. We report three patients in whom hypoxic vasoconstriction was apparently incomplete, resulting in a ''reversed'' ventilation-perfusion mismatch. Perfusion of the hypoxic lobe on the radionuclide scan was associated with metabolic alkalosis, pulmonary venous and pulmonary arterial hypertension in these patients

  4. Reverse amblyopia with atropine treatment.

    Science.gov (United States)

    Hainline, Bryan C; Sprunger, Derek C; Plager, David A; Neely, Daniel E; Guess, Matthew G

    2009-01-01

    Occlusion, pharmacologic pernalization and combined therapy have been documented in controlled studies to effectively treat amblyopia with few complications. However, there remain concerns about the effectiveness and complications when, as in this case, there are not standardized treatment protocols. A retrospective chart review of 133 consecutive patients in one community based ophthalmology practice treated for amblyopia was performed. Treatments evaluated were occlusion only, atropine penalization, and combination of occlusion and atropine. Reverse amblyopia was defined as having occured when the visual acuity of the sound eye was 3 LogMar units worse than visual acuity of the amblyopia eye after treatment. Improvement in vision after 6 months and 1 year of amblyopia therapy was similar among all three groups: 0.26 LogMar lines and 0.30 in the atropine group, 0.32 and 0.34 in the occlusion group, and 0.24 and 0.32 in the combined group. Eight (6%) patients demonstrated reverse amblyopia. The mean age of those who developed reverse amblyopia was 3.5 years, 1.5 years younger than the mean age of the study population, 7/8 had strabismic amblyopia, 6/8 were on daily atropine and had a mean refractive error of +4.77 diopters in the amblyopic eye and +5.06 diopters in the sound eye. Reverse amblyopia did not occur with occlusion only therapy. In this community based ophthalmology practice, atropine, patching, and combination therapy appear to be equally effective modalities to treat ambyopia. Highly hyperopic patients under 4 years of age with dense, strabismic amblyopia and on daily atropine appeared to be most at risk for development of reverse amblyopia.

  5. Reversible conversion of valence-tautomeric copper metal-organic frameworks dependent single-crystal-to-single-crystal oxidation/reduction: a redox-switchable catalyst for C-H bonds activation reaction.

    Science.gov (United States)

    Huang, Chao; Wu, Jie; Song, Chuanjun; Ding, Ran; Qiao, Yan; Hou, Hongwei; Chang, Junbiao; Fan, Yaoting

    2015-06-28

    Upon single-crystal-to-single-crystal (SCSC) oxidation/reduction, reversible structural transformations take place between the anionic porous zeolite-like Cu(I) framework and a topologically equivalent neutral Cu(I)Cu(II) mixed-valent framework. The unique conversion behavior of the Cu(I) framework endowed it as a redox-switchable catalyst for the direct arylation of heterocycle C-H bonds.

  6. Research on the influencing factors of reverse logistics carbon footprint under sustainable development.

    Science.gov (United States)

    Sun, Qiang

    2017-10-01

    With the concerns of ecological and circular economy along with sustainable development, reverse logistics has attracted the attention of enterprise. How to achieve sustainable development of reverse logistics has important practical significance of enhancing low carbon competitiveness. In this paper, the system boundary of reverse logistics carbon footprint is presented. Following the measurement of reverse logistics carbon footprint and reverse logistics carbon capacity is provided. The influencing factors of reverse logistics carbon footprint are classified into five parts such as intensity of reverse logistics, energy structure, energy efficiency, reverse logistics output, and product remanufacturing rate. The quantitative research methodology using ADF test, Johansen co-integration test, and impulse response is utilized to interpret the relationship between reverse logistics carbon footprint and the influencing factors more accurately. This research finds that energy efficiency, energy structure, and product remanufacturing rate are more capable of inhibiting reverse logistics carbon footprint. The statistical approaches will help practitioners in this field to structure their reverse logistics activities and also help academics in developing better decision models to reduce reverse logistics carbon footprint.

  7. Reversible Unfolding of Rhomboid Intramembrane Proteases.

    Science.gov (United States)

    Panigrahi, Rashmi; Arutyunova, Elena; Panwar, Pankaj; Gimpl, Katharina; Keller, Sandro; Lemieux, M Joanne

    2016-03-29

    Denaturant-induced unfolding of helical membrane proteins provides insights into their mechanism of folding and domain organization, which take place in the chemically heterogeneous, anisotropic environment of a lipid membrane. Rhomboid proteases are intramembrane proteases that play key roles in various diseases. Crystal structures have revealed a compact helical bundle with a buried active site, which requires conformational changes for the cleavage of transmembrane substrates. A dimeric form of the rhomboid protease has been shown to be important for activity. In this study, we examine the mechanism of refolding for two distinct rhomboids to gain insight into their secondary structure-activity relationships. Although helicity is largely abolished in the unfolded states of both proteins, unfolding is completely reversible for HiGlpG but only partially reversible for PsAarA. Refolding of both proteins results in reassociation of the dimer, with a 90% regain of catalytic activity for HiGlpG but only a 70% regain for PsAarA. For both proteins, a broad, gradual transition from the native, folded state to the denatured, partly unfolded state was revealed with the aid of circular dichroism spectroscopy as a function of denaturant concentration, thus arguing against a classical two-state model as found for many globular soluble proteins. Thermal denaturation has irreversible destabilizing effects on both proteins, yet reveals important functional details regarding substrate accessibility to the buried active site. This concerted biophysical and functional analysis demonstrates that HiGlpG, with a simple six-transmembrane-segment organization, is more robust than PsAarA, which has seven predicted transmembrane segments, thus rendering HiGlpG amenable to in vitro studies of membrane-protein folding. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  8. Rocuronium blockade reversal with sugammadex vs. neostigmine

    DEFF Research Database (Denmark)

    Wu, Xinmin; Oerding, Helle; Liu, Jin

    2014-01-01

    BACKGROUND: This study compared efficacy and safety of the selective relaxant binding agent sugammadex (2 mg/kg) with neostigmine (50 μg/kg) for neuromuscular blockade (NMB) reversal in Chinese and Caucasian subjects. METHODS: This was a randomized, active-controlled, multicenter, safety-assessor......BACKGROUND: This study compared efficacy and safety of the selective relaxant binding agent sugammadex (2 mg/kg) with neostigmine (50 μg/kg) for neuromuscular blockade (NMB) reversal in Chinese and Caucasian subjects. METHODS: This was a randomized, active-controlled, multicenter, safety...... twitch reappearance, after last rocuronium dose, subjects received sugammadex 2 mg/kg or neostigmine 50 μg/kg plus atropine 10-20 μg/kg, according to randomization. Primary efficacy variable was time from sugammadex/neostigmine to recovery of the train-of-four (TOF) ratio to 0.9. RESULTS: Overall, 230...... Chinese subjects (sugammadex, n = 119, neostigmine, n = 111); and 59 Caucasian subjects (sugammadex, n = 29, neostigmine, n = 30) had evaluable data. Geometric mean (95% CI) time to recovery to TOF ratio 0.9 was 1.6 (1.5-1.7) min with sugammadex vs 9.1 (8.0-10.3) min with neostigmine in Chinese subjects...

  9. Reversal agents in anaesthesia and critical care

    Directory of Open Access Journals (Sweden)

    Nibedita Pani

    2015-01-01

    Full Text Available Despite the advent of short and ultra-short acting drugs, an in-depth knowledge of the reversal agents used is a necessity for any anaesthesiologist. Reversal agents are defined as any drug used to reverse the effects of anaesthetics, narcotics or potentially toxic agents. The controversy on the routine reversal of neuromuscular blockade still exists. The advent of newer reversal agents like sugammadex have made the use of steroidal neuromuscular blockers like rocuronium feasible in rapid sequence induction situations. We made a review of the older reversal agents and those still under investigation for drugs that are regularly used in our anaesthesia practice.

  10. Reverse osmosis water purification system

    Science.gov (United States)

    Ahlstrom, H. G.; Hames, P. S.; Menninger, F. J.

    1986-01-01

    A reverse osmosis water purification system, which uses a programmable controller (PC) as the control system, was designed and built to maintain the cleanliness and level of water for various systems of a 64-m antenna. The installation operates with other equipment of the antenna at the Goldstone Deep Space Communication Complex. The reverse osmosis system was designed to be fully automatic; with the PC, many complex sequential and timed logic networks were easily implemented and are modified. The PC monitors water levels, pressures, flows, control panel requests, and set points on analog meters; with this information various processes are initiated, monitored, modified, halted, or eliminated as required by the equipment being supplied pure water.

  11. Trend towards reverse leach process

    International Nuclear Information System (INIS)

    Anon.

    1975-01-01

    The South African gold mining industry is making notable strides in improving recovery methods for both gold and uranium with significant additions to profits because of higher efficiencies and reductions in costs in the recovery processes. The most notable step on the gold side recently is the adoption of the reverse leach process at Buffelsfontein and Western Deep Levels. This process was pioneered at Hartebeesfontein as far back as 1975 and when introduced there resulted in a two and a half per cent improvement in recovery efficiencies. The essence of reverse leaching under which the uranium is recovered before the gold is the fact that the gold partly coated with iron oxide or locked in uranite, is exposed to be recovered later by cyanidation

  12. Reversible evolution of charged ergoregions

    Energy Technology Data Exchange (ETDEWEB)

    Kokkotas, K.; Spyrou, N.

    1987-07-01

    The reversible evolution of a charged rotating ergoregion, due to the injection into it of particles with mass-energy and angular momentum, is studied systematically. As in the uncharged case, a bulge always forms on the outer boundary of the ergoregion due to the latter's angular momentum. The behavior of the bulge's position, relative to the black hole's rotation axis and equatorial plane, is studied, on the basis of the cosmic censorship hypothesis, during the ergoregion's reversible evolution. The range of the permitted values of the ergoregion's linear dimensions along the rotation axis and perpendicular to it is specified. Finally the differences with the evolution of an uncharged ergoregion are pointed out and discussed.

  13. Malware analysis and reverse engineering

    OpenAIRE

    Šváb, Martin

    2014-01-01

    Focus of this thesis is reverse engineering in information technology closely linked with the malware analysis. It explains fundamentals of IA-32 processors architecture and basics of operating system Microsoft Windows. Main part of this thesis is dedicated to the malware analysis, including description of creating a tool for simplification of static part of the analysis. In Conclusion various approaches to the malware analysis, which were described in previous part of the thesis, are practic...

  14. How to play Reverse Hex

    DEFF Research Database (Denmark)

    Toft, Bjarne; Hayward, Ryan B.; Henderson, Philip

    2012-01-01

    We present new results on how to play Reverse Hex, also known as Rex, or Misère Hex, on n × n boards. We give new proofs – and strengthened versions – of Lagarias and Sleator’s theorem (for n × n boards, each player can prolong the game until the board is full, so the first/second player can alwa...

  15. Theory of field reversed configurations

    International Nuclear Information System (INIS)

    Steinhauer, L.C.

    1990-01-01

    This final report surveys the results of work conducted on the theory of field reversed configurations. This project has spanned ten years, beginning in early 1980. During this period, Spectra Technology was one of the leading contributors to the advances in understanding FRC. The report is organized into technical topic areas, FRC formation, equilibrium, stability, and transport. Included as an appendix are papers published in archival journals that were generated in the course of this report. 33 refs

  16. Reverse engineering of integrated circuits

    Science.gov (United States)

    Chisholm, Gregory H.; Eckmann, Steven T.; Lain, Christopher M.; Veroff, Robert L.

    2003-01-01

    Software and a method therein to analyze circuits. The software comprises several tools, each of which perform particular functions in the Reverse Engineering process. The analyst, through a standard interface, directs each tool to the portion of the task to which it is most well suited, rendering previously intractable problems solvable. The tools are generally used iteratively to produce a successively more abstract picture of a circuit, about which incomplete a priori knowledge exists.

  17. Risperidone-induced reversible neutropenia.

    Science.gov (United States)

    Kattalai Kailasam, Vasanth; Chima, Victoria; Nnamdi, Uchechukwu; Sharma, Kavita; Shah, Kairav

    2017-01-01

    This case report presents a 44-year-old man with a history of schizophrenia who developed neutropenia on risperidone therapy. The patient's laboratory reports showed a gradual decline of leukocytes and neutrophils after resolution and rechallenging. This was reversed with the discontinuation of risperidone and by switching to olanzapine. In this case report, we also discuss the updated evidence base for management of risperidone-induced neutropenia.

  18. Removal of radionuclides in drinking water by membrane treatment using ultrafiltration, reverse osmosis and electrodialysis reversal.

    Science.gov (United States)

    Montaña, M; Camacho, A; Serrano, I; Devesa, R; Matia, L; Vallés, I

    2013-11-01

    A pilot plant had been built to test the behaviour of ultrafiltration (UF), reverse osmosis (RO), and electrodialysis reversal (EDR) in order to improve the quality of the water supplied to Barcelona metropolitan area from the Llobregat River. This paper presents results from two studies to reduce natural radioactivity. The results from the pilot plant with four different scenarios were used to design the full-scale treatment plant built (SJD WTP). The samples taken at different steps of the treatment were analysed to determine gross alpha, gross beta and uranium activity. The results obtained revealed a significant improvement in the radiological water quality provided by both membrane techniques (RO and EDR showed removal rates higher than 60%). However, UF did not show any significant removal capacity for gross alpha, gross beta or uranium activities. RO was better at reducing the radiological parameters studied and this treatment was selected and applied at the full scale treatment plant. The RO treatment used at the SJD WTP reduced the concentration of both gross alpha and gross beta activities and also produced water of high quality with an average removal of 95% for gross alpha activity and almost 93% for gross beta activity at the treatment plant. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Domain reversal dynamics in ferromagnetic thin films of Co/Pd nanomultilayers

    International Nuclear Information System (INIS)

    Choe, Sug Bong; Kim, Dong Hyun; Shin, Sung Chul

    2002-01-01

    Domain reversal dynamics in ferromagnetic thin films has been quantitatively investigated by means of a magneto-optical microscope magnetometer (MOMM), capable of grabbing domain reversal patterns in real time under an applied magnetic field and of measuring local magnetic properties with 400-nm spatial resolution. The domain reversal behavior sensitively changed between wall-motion and nucleation-dominant behavior with changing multilayer structure of the Co-Pd multilayers. Quantitative analysis revealed that the contrasting reversal behavior was mainly caused by a sensitive change in wall-motion speed and that the reversal ratio of wall-motion speed over nucleation rate was a governing parameter for the contrasting domain reversal dynamics. The activation volumes of the wall-motion and nucleation processes were generally unequal, and the inequality was closely related with the domain dynamics. Based on a Monte-Carlo simulation, both the macroscopic magnetic properties and the local magnetic variation were responsible for the contrasting domain reversal behavior

  20. Artificial Self-Sufficient P450 in Reversed Micelles

    Directory of Open Access Journals (Sweden)

    Teruyuki Nagamune

    2010-04-01

    Full Text Available Cytochrome P450s are heme-containing monooxygenases that require electron transfer proteins for their catalytic activities. They prefer hydrophobic compounds as substrates and it is, therefore, desirable to perform their reactions in non-aqueous media. Reversed micelles can stably encapsulate proteins in nano-scaled water pools in organic solvents. However, in the reversed micellar system, when multiple proteins are involved in a reaction they can be separated into different micelles and it is then difficult to transfer electrons between proteins. We show here that an artificial self-sufficient cytochrome P450, which is an enzymatically crosslinked fusion protein composed of P450 and electron transfer proteins, showed micelle-size dependent catalytic activity in a reversed micellar system. Furthermore, the presence of thermostable alcohol dehydrogenase promoted the P450-catalyzed reaction due to cofactor regeneration.

  1. Reversal of liver fibrosis: From fiction to reality.

    Science.gov (United States)

    Zoubek, Miguel Eugenio; Trautwein, Christian; Strnad, Pavel

    2017-04-01

    In chronic liver diseases, an ongoing hepatocellular injury together with inflammatory reaction results in activation of hepatic stellate cells (HSCs) and increased deposition of extracellular matrix (ECM) termed as liver fibrosis. It can progress to cirrhosis that is characterized by parenchymal and vascular architectural changes together with the presence of regenerative nodules. Even at late stage, liver fibrosis is reversible and the underlying mechanisms include a switch in the inflammatory environment, elimination or regression of activated HSCs and degradation of ECM. While animal models have been indispensable for our understanding of liver fibrosis, they possess several important limitations and need to be further refined. A better insight into the liver fibrogenesis resulted in a large number of clinical trials aiming at reversing liver fibrosis, particularly in patients with non-alcoholic steatohepatitis. Collectively, the current developments demonstrate that reversal of liver fibrosis is turning from fiction to reality. Copyright © 2017. Published by Elsevier Ltd.

  2. SELECTED PROBLEMS OF REVERSE LOGISTICS IN POLAND

    OpenAIRE

    Agata Mesjasz-Lech

    2009-01-01

    This paper presents the essence of reverse logistics and directions of physical and information flows between logistic network partners. It also analyses effects of implementation of the principles of reverse logistics in Poland in the years 2004-2007

  3. Strand transfer and elongation of HIV-1 reverse transcription is facilitated by cell factors in vitro.

    Directory of Open Access Journals (Sweden)

    David Warrilow

    Full Text Available Recent work suggests a role for multiple host factors in facilitating HIV-1 reverse transcription. Previously, we identified a cellular activity which increases the efficiency of HIV-1 reverse transcription in vitro. Here, we describe aspects of the activity which shed light on its function. The cellular factor did not affect synthesis of strong-stop DNA but did improve downstream DNA synthesis. The stimulatory activity was isolated by gel filtration in a single fraction of the exclusion volume. Velocity-gradient purified HIV-1, which was free of detectable RNase activity, showed poor reverse transcription efficiency but was strongly stimulated by partially purified cell proteins. Hence, the cell factor(s did not inactivate an RNase activity that might degrade the viral genomic RNA and block completion of reverse transcription. Instead, the cell factor(s enhanced first strand transfer and synthesis of late reverse transcription suggesting it stabilized the reverse transcription complex. The factor did not affect lysis of HIV-1 by Triton X-100 in the endogenous reverse transcription (ERT system, and ERT reactions with HIV-1 containing capsid mutations, which varied the biochemical stability of viral core structures and impeded reverse transcription in cells, showed no difference in the ability to be stimulated by the cell factor(s suggesting a lack of involvement of the capsid in the in vitro assay. In addition, reverse transcription products were found to be resistant to exogenous DNase I activity when the active fraction was present in the ERT assay. These results indicate that the cell factor(s may improve reverse transcription by facilitating DNA strand transfer and DNA synthesis. It also had a protective function for the reverse transcription products, but it is unclear if this is related to improved DNA synthesis.

  4. Periodicity and Immortality in Reversible Computing

    OpenAIRE

    Kari , Jarkko; Ollinger , Nicolas

    2008-01-01

    Additional material available on the web at http://www.lif.univ-mrs.fr/~nollinge/rec/gnirut/; We investigate the decidability of the periodicity and the immortality problems in three models of reversible computation: reversible counter machines, reversible Turing machines and reversible one-dimensional cellular automata. Immortality and periodicity are properties that describe the behavior of the model starting from arbitrary initial configurations: immortality is the property of having at le...

  5. Midday reversal of equatorial ionospheric electric field

    Directory of Open Access Journals (Sweden)

    R. G. Rastogi

    1997-10-01

    Full Text Available A comparative study of the geomagnetic and ionospheric data at equatorial and low-latitude stations in India over the 20 year period 1956–1975 is described. The reversal of the electric field in the ionosphere over the magnetic equator during the midday hours indicated by the disappearance of the equatorial sporadic E region echoes on the ionograms is a rare phenomenon occurring on about 1% of time. Most of these events are associated with geomagnetically active periods. By comparing the simultaneous geomagnetic H field at Kodaikanal and at Alibag during the geomagnetic storms it is shown that ring current decreases are observed at both stations. However, an additional westward electric field is superimposed in the ionosphere during the main phase of the storm which can be strong enough to temporarily reverse the normally eastward electric field in the dayside ionosphere. It is suggested that these electric fields associated with the V×Bz electric fields originate at the magnetopause due to the interaction of the solar wind and the interplanetary magnetic field.

  6. Midday reversal of equatorial ionospheric electric field

    Directory of Open Access Journals (Sweden)

    R. G. Rastogi

    Full Text Available A comparative study of the geomagnetic and ionospheric data at equatorial and low-latitude stations in India over the 20 year period 1956–1975 is described. The reversal of the electric field in the ionosphere over the magnetic equator during the midday hours indicated by the disappearance of the equatorial sporadic E region echoes on the ionograms is a rare phenomenon occurring on about 1% of time. Most of these events are associated with geomagnetically active periods. By comparing the simultaneous geomagnetic H field at Kodaikanal and at Alibag during the geomagnetic storms it is shown that ring current decreases are observed at both stations. However, an additional westward electric field is superimposed in the ionosphere during the main phase of the storm which can be strong enough to temporarily reverse the normally eastward electric field in the dayside ionosphere. It is suggested that these electric fields associated with the V×Bz electric fields originate at the magnetopause due to the interaction of the solar wind and the interplanetary magnetic field.

  7. r-Universal reversible logic gates

    International Nuclear Information System (INIS)

    Vos, A de; Storme, L

    2004-01-01

    Reversible logic plays a fundamental role both in ultra-low power electronics and in quantum computing. It is therefore important to know which reversible logic gates can be used as building block for the reversible implementation of an arbitrary boolean function and which cannot

  8. THEORETICAL FRAMES FOR DESIGNING REVERSE LOGISTICS PROCESSES

    OpenAIRE

    Janusz K. Grabara; Sebastian Kot

    2009-01-01

    Logistics processes of return flow became more and more important in present business practice. Because of better customer satisfaction, environmental and financial aspects many enterprises deal with reverse logistics performance. The paper is a literature review focused on the design principles of reverse logistics processes Keywords: reverse logistics, designing.

  9. Prefix reversals on binary and ternary strings

    NARCIS (Netherlands)

    Hurkens, C.A.J.; van Iersel, L.J.J.; Keijsper, J.C.M.; Kelk, S.M.; Stougie, L.; Tromp, J.T.

    2007-01-01

    Given a permutation $\\pi$, the application of prefix reversal $f^{(i)}$ to $\\pi$ reverses the order of the first $i$ elements of $\\pi$. The problem of sorting by prefix reversals (also known as pancake flipping), made famous by Gates and Papadimitriou (Discrete Math., 27 (1979), pp. 47–57), asks

  10. Prefix reversals on binary and ternary strings

    NARCIS (Netherlands)

    Hurkens, C.A.J.; Iersel, van L.J.J.; Keijsper, J.C.M.; Kelk, S.M.; Stougie, L.; Tromp, J.T.

    2007-01-01

    Given a permutation $\\pi$, the application of prefix reversal $f^{(i)}$ to $\\pi$ reverses the order of the first $i$ elements of $\\pi$. The problem of sorting by prefix reversals (also known as pancake flipping), made famous by Gates and Papadimitriou (Discrete Math., 27 (1979), pp. 47–57), asks for

  11. The role of educational strategies to reverse the inverse ...

    African Journals Online (AJOL)

    We also present a conceptual framework for developing best practice educational strategies to reverse the inverse performance spiral in academically isolated rural hospitals. Doctors felt that participation in relevant learning activities improved their competence, increased the levels of job satisfaction they experienced ...

  12. Some functional inequalities on non-reversible Finsler manifolds

    Indian Academy of Sciences (India)

    SHIN-ICHI OHTA

    2017-11-13

    Nov 13, 2017 ... In the reversible case, these inequalities were obtained by. Cavalletti and ... active area. The classical Riemannian theory has been generalized to weighted Rieman- .... Define the dual Minkowski norm F. ∗: T. ∗ .... We also define Ric∞(v) and Ricn(v) as the limits and set RicN (cv) := c2RicN (v) for c ≥ 0.

  13. Simulated Analysis of Linear Reversible Enzyme Inhibition with SCILAB

    Science.gov (United States)

    Antuch, Manuel; Ramos, Yaquelin; Álvarez, Rubén

    2014-01-01

    SCILAB is a lesser-known program (than MATLAB) for numeric simulations and has the advantage of being free software. A challenging software-based activity to analyze the most common linear reversible inhibition types with SCILAB is described. Students establish typical values for the concentration of enzyme, substrate, and inhibitor to simulate…

  14. Closing the Loop : Reverse supply chain management andproduct return processes in electronics retailing

    OpenAIRE

    Gorskova, Julija; Ortega, Edrion

    2012-01-01

    Abstract Problem There is a gap in the knowledge concerning reverse product flows due to a lack of research and empirical data in the field of reverse supply chain management in general. Furthermore, more research is needed to investigate the factors influencing the decision making process regarding the right reverse supply chain recovery option choice for companies in order to close the supply chain loop. Processing product returns has become a critical activity for organisations as the volu...

  15. Repeatable Reverse Engineering with PANDA

    Science.gov (United States)

    2015-12-08

    necessary layout information for the Android 2.3 and 4.2 SDK kernels. See Section IV-C for an example of the kind of deep reverse engineering of Android apps ...code re-use and simplifying complex analysis development. We demonstrate PANDA’s effectiveness via a number of use cases, including enabling an old but...continue to function. 2) Identify critical vulnerabilities . 3) Understand the true purpose and actions of code. It is common for legacy code to stop

  16. Corrosion protected reversing heat exchanger

    International Nuclear Information System (INIS)

    Zawierucha, R.

    1984-01-01

    A reversing heat exchanger of the plate and fin type having multiple aluminum parting sheets in a stacked arrangement with corrugated fins separating the sheets to form multiple flow paths, means for closing the ends of the sheets, an input manifold arrangement of headers for the warm end of of the exchanger and an output manifold arrangement for the cold end of the exchanger with the input air feed stream header and the waste gas exhaust header having an alloy of zinc and aluminum coated on the inside surface for providing corrosion protection to the stack

  17. Presbycusis: reversible with anesthesia drugs?

    Science.gov (United States)

    Kocher, Carl A

    2009-02-01

    Age-related hearing impairment, or presbycusis, is a degenerative condition not currently treatable by medication. It is therefore significant that the author, as a patient, experienced a reversal of high-frequency hearing loss during a 2-day period following abdominal surgery with general anesthesia. This report documents the surgery and the subsequent restoration of hearing, which was bilateral and is estimated to have exceeded 50dB at 4kHz. A possible role is noted for anesthetic agents such as lidocaine, propofol, or fentanyl. This experience may hold a clue for research toward the development of medical treatments for presbycusis.

  18. Field-reversed mirror reactor

    International Nuclear Information System (INIS)

    Carlson, G.A.

    1978-01-01

    The reactor design is a multicell arrangement wherein a series of field-reversed plasma layers are arranged along the axis of a long superconducting solenoid which provides the background magnetic field. Normal copper mirror coils and Ioffe bars placed at the first wall radius provide shallow axial and radial magnetic wells for each plasma layer. Each of 11 plasma layers requires the injection of 3.6 MW of 200 keV deuterium and tritium and produces 20 MW of fusion power. The reactor has a net electric output of 74 MWe and an estimated direct capital cost of $1200/kWe

  19. Kinematic reversal schemes for the geomagnetic dipole.

    Science.gov (United States)

    Levy, E. H.

    1972-01-01

    Fluctuations in the distribution of cyclonic convective cells, in the earth's core, can reverse the sign of the geomagnetic field. Two kinematic reversal schemes are discussed. In the first scheme, a field maintained by cyclones concentrated at low latitude is reversed by a burst of cyclones at high latitude. Conversely, in the second scheme, a field maintained predominantly by cyclones in high latitudes is reversed by a fluctuation consisting of a burst of cyclonic convection at low latitude. The precise fluid motions which produce the geomagnetic field are not known. However, it appears that, whatever the details are, a fluctuation in the distribution of cyclonic cells over latitude can cause a geomagnetic reversal.

  20. A comparison of ROChem reverse osmosis and spiral wound reverse osmosis membrane modules

    International Nuclear Information System (INIS)

    Siler, J.L.

    1992-01-01

    Testing of the ROChem Disc Tube reg-sign reverse osmosis (RO) module's performance on biologically active feed waters has been completed. Both the ROChem module (using Filmtec standard-rejection seawater membranes) and the Filmtec spiral-wound membrane module (using Filmtec high-rejection seawater membranes) were tested with stimulant solutions containing typical bacteria and metal hydroxide levels found in the F/H Effluent Treatment Facility (ETF) influent. Results indicate that the ROChem module gave superior performance over the spiral-wound module. Water flux losses were reduced by over 30% for water recoveries above 40%

  1. Reverse case study: to think like a nurse.

    Science.gov (United States)

    Beyer, Deborah A

    2011-01-01

    Reverse case study is a collaborative, innovative, active learning strategy that nurse educators can use in the classroom. Groups of students develop a case study and a care plan from a list of medications and a short two- to three-sentence scenario. The students apply the nursing process to thoroughly develop a complete case study written as a concept map. The strategy builds on previous learned information and applies the information to new content, thus promoting critical thinking and problem solving. Reverse case study has been used in both associate and baccalaureate nursing degree theory courses to generate discussion and assist students in thinking like a nurse. 2011, SLACK Incorporated.

  2. Logistics Management: New trends in the Reverse Logistics

    Science.gov (United States)

    Antonyová, A.; Antony, P.; Soewito, B.

    2016-04-01

    Present level and quality of the environment are directly dependent on our access to natural resources, as well as their sustainability. In particular production activities and phenomena associated with it have a direct impact on the future of our planet. Recycling process, which in large enterprises often becomes an important and integral part of the production program, is usually in small and medium-sized enterprises problematic. We can specify a few factors, which have direct impact on the development and successful application of the effective reverse logistics system. Find the ways to economically acceptable model of reverse logistics, focusing on converting waste materials for renewable energy, is the task in progress.

  3. Theory of field-reversed configurations

    International Nuclear Information System (INIS)

    Steinhauer, L.C.

    1993-01-01

    This report summarizes results from the theoretical program on field reversed configurations (FRC) at STI Optronics. The program, which has spanned the last 13 years, has included analytical as well as computational components. It has led to published papers on every major topic of FRC theory. The report is outlined to summarize results from each of these topic areas: formation, equilibrium, stability, and confinement. Also briefly described are Steinhauer's activities as Compact Toroid Theory Listening Post. Appendix A is a brief listing of the major advances achieved in this program. Attached at the back of this report is a collection of technical papers in archival journals that resulted from work in this program. The discussion within each subsection is given chronologically in order to give a historical sense of the evolution of understanding of FRC physics

  4. Bio-inspired reversible underwater adhesive.

    Science.gov (United States)

    Zhao, Yanhua; Wu, Yang; Wang, Liang; Zhang, Manman; Chen, Xuan; Liu, Minjie; Fan, Jun; Liu, Junqiu; Zhou, Feng; Wang, Zuankai

    2017-12-20

    The design of smart surfaces with switchable adhesive properties in a wet environment has remained a challenge in adhesion science and materials engineering. Despite intense demands in various industrial applications and exciting progress in mimicking the remarkable wet adhesion through the delicate control of catechol chemistry, polyelectrolyte complex, and supramolecular architectures, the full recapitulation of nature's dynamic function is limited. Here, we show a facile approach to synthesize bioinspired adhesive, which entails the reversible, tunable, and fast regulation of the wet adhesion on diverse surfaces. The smart wet adhesive takes advantage of the host-guest molecular interaction and the adhesive nature of catechol chemistry, as well as the responsive polymer, allowing for screening and activation of the interfacial interaction simply by a local temperature trigger in an on-demand manner. Our work opens up an avenue for the rational design of bioinspired adhesives with performances even beyond nature.

  5. Theta, time reversal and temperature

    Energy Technology Data Exchange (ETDEWEB)

    Gaiotto, Davide [Perimeter Institute for Theoretical Physics,Waterloo, Ontario, N2L 2Y5 (Canada); Kapustin, Anton [Walter Burke Institute for Theoretical Physics, California Institute of Technology,Pasadena, CA 91125 (United States); Komargodski, Zohar [Department of Particle Physics and Astrophysics, Weizmann Institute of Science,Rehovot 76100 (Israel); Seiberg, Nathan [School of Natural Sciences, Institute for Advanced Study,Princeton, NJ 08540 (United States)

    2017-05-17

    SU(N) gauge theory is time reversal invariant at θ=0 and θ=π. We show that at θ=π there is a discrete ’t Hooft anomaly involving time reversal and the center symmetry. This anomaly leads to constraints on the vacua of the theory. It follows that at θ=π the vacuum cannot be a trivial non-degenerate gapped state. (By contrast, the vacuum at θ=0 is gapped, non-degenerate, and trivial.) Due to the anomaly, the theory admits nontrivial domain walls supporting lower-dimensional theories. Depending on the nature of the vacuum at θ=π, several phase diagrams are possible. Assuming area law for space-like loops, one arrives at an inequality involving the temperatures at which CP and the center symmetry are restored. We also analyze alternative scenarios for SU(2) gauge theory. The underlying symmetry at θ=π is the dihedral group of 8 elements. If deconfined loops are allowed, one can have two O(2)-symmetric fixed points. It may also be that the four-dimensional theory around θ=π is gapless, e.g. a Coulomb phase could match the underlying anomalies.

  6. Theta, time reversal and temperature

    International Nuclear Information System (INIS)

    Gaiotto, Davide; Kapustin, Anton; Komargodski, Zohar; Seiberg, Nathan

    2017-01-01

    SU(N) gauge theory is time reversal invariant at θ=0 and θ=π. We show that at θ=π there is a discrete ’t Hooft anomaly involving time reversal and the center symmetry. This anomaly leads to constraints on the vacua of the theory. It follows that at θ=π the vacuum cannot be a trivial non-degenerate gapped state. (By contrast, the vacuum at θ=0 is gapped, non-degenerate, and trivial.) Due to the anomaly, the theory admits nontrivial domain walls supporting lower-dimensional theories. Depending on the nature of the vacuum at θ=π, several phase diagrams are possible. Assuming area law for space-like loops, one arrives at an inequality involving the temperatures at which CP and the center symmetry are restored. We also analyze alternative scenarios for SU(2) gauge theory. The underlying symmetry at θ=π is the dihedral group of 8 elements. If deconfined loops are allowed, one can have two O(2)-symmetric fixed points. It may also be that the four-dimensional theory around θ=π is gapless, e.g. a Coulomb phase could match the underlying anomalies.

  7. Optimized reversible binary-coded decimal adders

    DEFF Research Database (Denmark)

    Thomsen, Michael Kirkedal; Glück, Robert

    2008-01-01

    Abstract Babu and Chowdhury [H.M.H. Babu, A.R. Chowdhury, Design of a compact reversible binary coded decimal adder circuit, Journal of Systems Architecture 52 (5) (2006) 272-282] recently proposed, in this journal, a reversible adder for binary-coded decimals. This paper corrects and optimizes...... their design. The optimized 1-decimal BCD full-adder, a 13 × 13 reversible logic circuit, is faster, and has lower circuit cost and less garbage bits. It can be used to build a fast reversible m-decimal BCD full-adder that has a delay of only m + 17 low-power reversible CMOS gates. For a 32-decimal (128-bit....... Keywords: Reversible logic circuit; Full-adder; Half-adder; Parallel adder; Binary-coded decimal; Application of reversible logic synthesis...

  8. Kinetic Line Voronoi Operations and Their Reversibility

    DEFF Research Database (Denmark)

    Mioc, Darka; Anton, François; Gold, Christopher

    2010-01-01

    In Geographic Information Systems the reversibility of map update operations has not been explored yet. In this paper we are using the Voronoi based Quad-edge data structure to define reversible map update operations. The reversibility of the map operations has been formalised at the lowest level...... mechanisms and dynamic map visualisations. In order to use the reversibility within the kinetic Voronoi diagram of points and open oriented line segments, we need to assure that reversing the map commands will produce exactly the changes in the map equivalent to the previous map states. To prove...... that reversing the map update operations produces the exact reverse changes, we show an isomorphism between the set of complex operations on the kinetic Voronoi diagram of points and open oriented line segments and the sets of numbers of new / deleted Voronoi regions induced by these operations, and its...

  9. Charge-reversal nanoparticles: novel targeted drug delivery carriers.

    Science.gov (United States)

    Chen, Xinli; Liu, Lisha; Jiang, Chen

    2016-07-01

    Spurred by significant progress in materials chemistry and drug delivery, charge-reversal nanocarriers are being developed to deliver anticancer formulations in spatial-, temporal- and dosage-controlled approaches. Charge-reversal nanoparticles can release their drug payload in response to specific stimuli that alter the charge on their surface. They can elude clearance from the circulation and be activated by protonation, enzymatic cleavage, or a molecular conformational change. In this review, we discuss the physiological basis for, and recent advances in the design of charge-reversal nanoparticles that are able to control drug biodistribution in response to specific stimuli, endogenous factors (changes in pH, redox gradients, or enzyme concentration) or exogenous factors (light or thermos-stimulation).

  10. Early reversal cells in adult human bone remodeling

    DEFF Research Database (Denmark)

    Abdelgawad, Mohamed Essameldin; Delaissé, Jean-Marie; Hinge, Maja

    2016-01-01

    The mechanism coupling bone resorption and formation is a burning question that remains incompletely answered through the current investigations on osteoclasts and osteoblasts. An attractive hypothesis is that the reversal cells are likely mediators of this coupling. Their nature is a big matter...... of debate. The present study performed on human cancellous bone is the first one combining in situ hybridization and immunohistochemistry to demonstrate their osteoblastic nature. It shows that the Runx2 and CD56 immunoreactive reversal cells appear to take up TRAcP released by neighboring osteoclasts....... Earlier preclinical studies indicate that reversal cells degrade the organic matrix left behind by the osteoclasts and that this degradation is crucial for the initiation of the subsequent bone formation. To our knowledge, this study is the first addressing these catabolic activities in adult human bone...

  11. Performance evaluation of reverse logistics: A case of LPG agency

    Directory of Open Access Journals (Sweden)

    Kottala Sri Yogi

    2015-12-01

    Full Text Available Majority of the manufacturing companies are incorporating the practice of reverse logistics in their value chain. In manufacturing processes, the concept of reverse logistics plays a vital role in enhancing the company’s profit margin for sustainable business growth. For every company, there is a need of performance measurement system to be established as successful business tool. However to predict better results, how smartly the inputs for the transformation or business process are being effectively and efficiently used has to be analyzed. Drawing attention to the growing popularity in adapting the best practices of reverse logistics among different manufacturing industries, this paper aims to build a methodology in order to measure the performance of liquefied petroleum gas (LPG agencies. To do so, it has undertaken the Asian emerging market-India as a case study and improved the understanding of performance measurement in reverse logistics to refilling LPG cylinders. Further, it has suggested a framework affecting the implementation of reverse logistics activities and its network.

  12. The behavioural consequences of sex reversal in dragons

    Science.gov (United States)

    Li, Hong; Holleley, Clare E.; Elphick, Melanie; Georges, Arthur

    2016-01-01

    Sex differences in morphology, physiology, and behaviour are caused by sex-linked genes, as well as by circulating sex-steroid levels. Thus, a shift from genotypic to environmental sex determination may create an organism that exhibits a mixture of male-like and female-like traits. We studied a lizard species (Central Bearded Dragon, Pogona vitticeps), in which the high-temperature incubation of eggs transforms genetically male individuals into functional females. Although they are reproductively female, sex-reversed dragons (individuals with ZZ genotype reversed to female phenotype) resemble genetic males rather than females in morphology (relative tail length), general behaviour (boldness and activity level), and thermoregulatory tactics. Indeed, sex-reversed ‘females’ are more male-like in some behavioural traits than are genetic males. This novel phenotype may impose strong selection on the frequency of sex reversal within natural populations, facilitating rapid shifts in sex-determining systems. A single period of high incubation temperatures (generating thermally induced sex reversal) can produce functionally female individuals with male-like (or novel) traits that enhance individual fitness, allowing the new temperature-dependent sex-determining system to rapidly replace the previous genetically based one.

  13. An analytic network process-based multicriteria decision making model for a reverse supply chain

    DEFF Research Database (Denmark)

    Govindan, Kannan; Sarkis, J.; Palaniappan, M.

    2013-01-01

    Reverse logistics has emerged as an important dimension for organizations to build their strategic advantage. Part of this effort relies on potentially outsourcing these activities. With this competitive issue in mind, this paper presents a multistep process to select a third-party reverse logistic...

  14. Reversal of diaschisis by zolpidem

    International Nuclear Information System (INIS)

    Claus, R.P.; Nel, H.W.; Sathekge, M.

    2004-01-01

    Full text: Introduction: Recent literature has reported on clinical improvement after zolpidem, a GABAergic anti insomnia drug, in brain injury and stroke patients. In this study, the effect of zolpidem on crossed cerebellar diaschisis was investigated in such patients. Method: Four patients with crossed cerebellar diaschisis after brain injury or stroke were investigated before and after application of 10 mg zolpidem by 99mTc HMPAO brain SPECT. Result: Apart from clinical improvements, 99mTc HMPAO brain SPECT studies showed reversal of the crossed cerebellar diaschisis and improvement of perfusion defects after zolpidem. Conclusion: 99mTc HMPAO brain SPECT may have a role to pre-select brain injury and stroke patients who will benefit clinically from zolpidem therapy. (author)

  15. Model of reverse steam generator

    International Nuclear Information System (INIS)

    Malasek, V.; Manek, O.; Masek, V.; Riman, J.

    1987-01-01

    The claim of Czechoslovak discovery no. 239272 is a model designed for the verification of the properties of a reverse steam generator during the penetration of water, steam-water mixture or steam into liquid metal flowing inside the heat exchange tubes. The design may primarily be used for steam generators with a built-in inter-tube structure. The model is provided with several injection devices configured in different heat exchange tubes, spaced at different distances along the model axis. The design consists in that between the pressure and the circumferential casings there are transverse partitions and that in one chamber consisting of the circumferential casings, pressure casing and two adjoining partitions there is only one passage of the injection device through the inter-tube space. (Z.M.). 1 fig

  16. Systemic Thrombolysis in Acute Ischemic Stroke after Dabigatran Etexilate Reversal with Idarucizumab—A Case Report

    DEFF Research Database (Denmark)

    Tireli, Derya; He, Jun; Nordling, Mette Maria

    2017-01-01

    Introduction Idarucizumab is a reversal agent for dabigatran etexilate. By reversing the anticoagulating effect of dabigatran etexilate with idarucizumab (Praxbind), patients presenting with an acute ischemic stroke can now be eligible for thrombolysis. Patient We describe our experience with ida......Introduction Idarucizumab is a reversal agent for dabigatran etexilate. By reversing the anticoagulating effect of dabigatran etexilate with idarucizumab (Praxbind), patients presenting with an acute ischemic stroke can now be eligible for thrombolysis. Patient We describe our experience...... of embolic stroke in patients with atrial fibrillation. Dabigatran etexilate is an oral thrombin inhibitor that can be reversed by idarucizumab. Idarucizumab, a monoclonal antibody fragment, directly binds dabigatran etexilate and neutralizes its activity. Conclusion Reversal of dabigatran etexilate using...

  17. Analysis on reverse fault activation and water inrush possibility for coal mining above confined aquifer in a mining area%某矿区带压开采逆断层活化及突水性分析

    Institute of Scientific and Technical Information of China (English)

    卜万奎; 徐慧

    2011-01-01

    According to the geological characteristics of 732 working face in a mining area,a mechanical model was built,and the expression for normal stress and shear stress on the fault was given respectively.By calculating the normal stress and shear stress on F16 reverse fault in excavation process,it is obtained that additional normal stress and additional shear stress is produced.Additional normal stress makes the tensional fracture emergence and development within F16 fault,while additional shear stress makes the shear fracture opening within F16 fault and makes shear joint opening on both parts of F16 fault.These results lead to water permeability improved within F16 fault.On this basis,failure distribution of coal roof and seepage feature of coal floor was simulated by using RFPA2D-Flow software.The results show that there is no connected fracture channel between aquifer on other part and working face in excavation process,because the shallow depths of F16 reverse fault is compactly closed and shale on coal floor isn't destroyed.Ordovician limestone water can't burst into working face and the seepage flow on coal floor is not enough to lead to water inrush accident.%根据某矿区732工作面的实际地质特征,建立了力学模型,给出了断层位置法向应力和剪应力的计算公式,计算了该矿区在开采过程中F16逆断层面上的法向应力和剪应力,得出:随着732工作面的开挖,F16逆断层面产生附加法向应力和附加剪应力,附加的法向应力使得断层带内张性裂隙产生与发展,附加的剪应力使得断层带内剪切裂隙和断层两侧的剪节理张开,透水性增强。在此基础上,利用RFPA2D-Flow有限元软件模拟了732工作面开采过程中顶板破坏情况及底板渗流特征,结果表明:732工作面开挖过程中,由于F16逆断层浅部紧闭不导

  18. Reversible arithmetic logic unit for quantum arithmetic

    DEFF Research Database (Denmark)

    Thomsen, Michael Kirkedal; Glück, Robert; Axelsen, Holger Bock

    2010-01-01

    This communication presents the complete design of a reversible arithmetic logic unit (ALU) that can be part of a programmable reversible computing device such as a quantum computer. The presented ALU is garbage free and uses reversible updates to combine the standard reversible arithmetic...... and logical operations in one unit. Combined with a suitable control unit, the ALU permits the construction of an r-Turing complete computing device. The garbage-free ALU developed in this communication requires only 6n elementary reversible gates for five basic arithmetic-logical operations on two n......-bit operands and does not use ancillae. This remarkable low resource consumption was achieved by generalizing the V-shape design first introduced for quantum ripple-carry adders and nesting multiple V-shapes in a novel integrated design. This communication shows that the realization of an efficient reversible...

  19. Principles of a reversible programming language

    DEFF Research Database (Denmark)

    Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

    2008-01-01

    The principles of reversible programming languages are explicated and illustrated with reference to the design of a high-level imperative language, Janus. The fundamental properties for such languages include backward as well as forward determinism and reversible updates of data. The unique design...... languages, and demonstrate this for Janus. We show the practicality of the language by implementation of a reversible fast Fourier transform. Our results indicate that the reversible programming paradigm has fundamental properties that are relevant to many different areas of computer science....... features of the language include explicit post-condition assertions, direct access to an inverse semantics and the possibility of clean (i.e., garbage-free) computation of injective functions. We suggest the clean simulation of reversible Turing machines as a criterion for computing strength of reversible...

  20. Securing Biometric Images using Reversible Watermarking

    OpenAIRE

    Thampi, Sabu M.; Jacob, Ann Jisma

    2011-01-01

    Biometric security is a fast growing area. Protecting biometric data is very important since it can be misused by attackers. In order to increase security of biometric data there are different methods in which watermarking is widely accepted. A more acceptable, new important development in this area is reversible watermarking in which the original image can be completely restored and the watermark can be retrieved. But reversible watermarking in biometrics is an understudied area. Reversible ...

  1. Removal of radionuclides from liquid streams by reverse osmosis

    International Nuclear Information System (INIS)

    Deshmukh, U.A.; Ramachandhran, V.; Misra, B.M.

    1987-01-01

    Separation of radionuclides in trace concentrations by cellulose acetate membranes has been under investigation in this laboratory, and the behaviour of some important radionuclides such as 137 Cs and 90 Sr under reverse osmosis has been reported earlier. The present work deals with a few other typical radionuclides such as 60 Co, 103 Ru and 131 I which are not fully amenable to conventional methods for their removal. Separation of these radionuclides from liquid streams by the reverse osmosis process was studied using a small reverse osmosis test cell. Various parameters like membrane porosity, applied pressure and feed activity levels were investigated. Cellulose acetate membranes offer reasonable separation of 60 Co, 103 Ru and 131 I radionuclides, indicating the potential of reverse osmosis for treatment of effluents containing these radioisotopes. The percent separation is found to be in the order of Co > Ru > I. The percent radioactive separation improves with increases in feed activity. The performance data are explained in terms of solution-diffusion mechanism. It appears that the separation of radionuclides is not governed by diffusion alone, but by the interaction of solutes with the membranes. (author)

  2. Magnetization reversal processes of single nanomagnets and their energy barrier

    International Nuclear Information System (INIS)

    Krone, P.; Makarov, D.; Albrecht, M.; Schrefl, T.; Suess, D.

    2010-01-01

    Micromagnetic simulations were performed to investigate the influence of geometry and magnetic anisotropy constant on energy barrier and magnetization reversal mechanism of individual bits important for the bit patterned media concept in magnetic data storage. It is shown that dependency of the energy barrier on magnetic and geometric properties of bits can be described by an analytical approach in the case of quasi-coherent magnetization rotation process. However, when the bit size exceeds a critical size, for which an incoherent magnetization reversal is preferred, the analytical approach becomes invalid and no self-consistent theory is available. By systematically investigating the influence of bit size on the magnetization reversal mode, it was found that the transition from quasi-coherent to incoherent magnetization reversal mode can still be described analytically if an activation volume is considered instead of the bit volume. In this case, the nucleation volume is an important parameter determining thermal stability of the bit. If the volume of the bit is larger than twice the activation volume, the energy barrier stays nearly constant; with further increase in bit size, no gain in thermal stability can be achieved.

  3. Stabilization of Reversed Replication Forks by Telomerase Drives Telomere Catastrophe.

    Science.gov (United States)

    Margalef, Pol; Kotsantis, Panagiotis; Borel, Valerie; Bellelli, Roberto; Panier, Stephanie; Boulton, Simon J

    2018-01-25

    Telomere maintenance critically depends on the distinct activities of telomerase, which adds telomeric repeats to solve the end replication problem, and RTEL1, which dismantles DNA secondary structures at telomeres to facilitate replisome progression. Here, we establish that reversed replication forks are a pathological substrate for telomerase and the source of telomere catastrophe in Rtel1 -/- cells. Inhibiting telomerase recruitment to telomeres, but not its activity, or blocking replication fork reversal through PARP1 inhibition or depleting UBC13 or ZRANB3 prevents the rapid accumulation of dysfunctional telomeres in RTEL1-deficient cells. In this context, we establish that telomerase binding to reversed replication forks inhibits telomere replication, which can be mimicked by preventing replication fork restart through depletion of RECQ1 or PARG. Our results lead us to propose that telomerase inappropriately binds to and inhibits restart of reversed replication forks within telomeres, which compromises replication and leads to critically short telomeres. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Combining or Separating Forward and Reverse Logistics

    DEFF Research Database (Denmark)

    Herbert-Hansen, Zaza Nadja Lee; Larsen, Samuel; Nielsen, Anders

    2018-01-01

    Purpose – While forward logistics handles and manages the flow of goods downstream in the supply chain from suppliers to customers, reverse logistics (RL) manages the flow of returned goods upstream. A firm can combine reverse logistics with forward logistics, keep the flows separated, or choose......-research addresses intra-RL issues while the relationship between forward and reverse logistics is under-researched. This paper contributes to RL-theory by identifying the contextual factors that determine the most advantageous relationship between forward and reverse logistics, and proposes a novel decision making...

  5. Interaction of HIV-1 reverse transcriptase ribonuclease H with an acylhydrazone inhibitor.

    Science.gov (United States)

    Gong, Qingguo; Menon, Lakshmi; Ilina, Tatiana; Miller, Lena G; Ahn, Jinwoo; Parniak, Michael A; Ishima, Rieko

    2011-01-01

    HIV-1 reverse transcriptase is a bifunctional enzyme, having both DNA polymerase (RNA- and DNA-dependent) and ribonuclease H activities. HIV-1 reverse transcriptase has been an exceptionally important target for antiretroviral therapeutic development, and nearly half of the current clinically used antiretrovirals target reverse transcriptase DNA polymerase. However, no inhibitors of reverse transcriptase ribonuclease H are on the market or in preclinical development. Several drug-like small molecule inhibitors of reverse transcriptase ribonuclease H have been described, but little structural information is available about the interactions between reverse transcriptase ribonuclease H and inhibitors that exhibit antiviral activity. In this report, we describe NMR studies of the interaction of a new ribonuclease H inhibitor, BHMP07, with a catalytically active HIV-1 reverse transcriptase ribonuclease H domain fragment. We carried out solution NMR experiments to identify the interaction interface of BHMP07 with the ribonuclease H domain fragment. Chemical shift changes of backbone amide signals at different BHMP07 concentrations clearly demonstrate that BHMP07 mainly recognizes the substrate handle region in the ribonuclease H fragment. Using ribonuclease H inhibition assays and reverse transcriptase mutants, the binding specificity of BHMP07 was compared with another inhibitor, dihydroxy benzoyl naphthyl hydrazone. Our results provide a structural characterization of the ribonuclease H inhibitor interaction and are likely to be useful for further improvements of the inhibitors. © 2010 John Wiley & Sons A/S.

  6. Arctigenin reduces neuronal responses in the somatosensory cortex via the inhibition of non-NMDA glutamate receptors

    OpenAIRE

    Borbély, S; Jocsak, Gergely; Moldovan, Kinga; Sedlak, Lucie; Preininger, Eva; Boldizsar, Imre; Toth, Attila; Atlason, Palmi T; Molnar, Elek; Vilagi, Ildiko

    2016-01-01

    Lignans are biologically active phenolic compounds related to lignin, produced in different plants. Arctigenin, a dibenzylbutyrolactone-type lignan, has been used as a neuroprotective agent for the treatment of encephalitis. Previous studies of cultured rat cerebral cortical neurones raised the possibility that arctigenin inhibits kainate-induced excitotoxicity. The aims of the present study were: 1) to analyse the effect of arctigenin on normal synaptic activity in ex vivo brain slices, 2) t...

  7. Reversible pumped hydro - benefits and challenges

    Energy Technology Data Exchange (ETDEWEB)

    Nielsen, Torbjoern K.; Walseth, Eve C.

    2010-07-01

    Full text: The Norwegian hydro power system is dominated with high head turbines, Pelton and Francis with high capacity in the reservoirs. Originally they were built for secure energy supply. In the system there are also reversible pump turbine (RPT) plants where in times with spare energy, made it possible to pump water from the lower reservoir to the higher. Again the idea was to secure energy supply, which meant pumping in early autumn to fill the reservoirs for winter. In the recent years, a more active use of the RPT plants has been actualized. The free market made price difference between night and day interesting, hence a more frequent pumping was desirable. In the coming years, new-renewable energy sources will utterly enhance a more active use of the RPT plants. More active use of the RPT plants means more frequent starts and stops, both in pumping and in turbine mode. There are a lot of challenges in adopting a new strategy for operating the machinery. More effective start equipment is required. The machinery will be exposed to more frequent dynamic loads; the turbines will be run at part- and full load. The existing RPT plants are connected to huge reservoirs. That means the RPTs are not only for short sighted power regulations, as many RPT-plants in Europe, but are also capable for a substantial energy production. In Norway, the nature is very suitable for RPT plants, both in connection with existing power plants, were reservoirs and conduits are already established, and standing alone with a minimum of energy production. RPTs are, as a design, a compromise between effective generating and stable as well as effective pumping. Stable pumping often results in very steep flow-speed characteristics when operating as a turbine. When dealing with hydraulic transients these characteristics cause a higher change in flow and torque leading to instability during start-up and possible off-design operation point. The instability slows down the synchronization

  8. Determination of a selection of anti-epileptic drugs and two active metabolites in whole blood by reversed phase UPLC-MS/MS and some examples of application of the method in forensic toxicology cases.

    Science.gov (United States)

    Karinen, Ritva; Vindenes, Vigdis; Hasvold, Inger; Olsen, Kirsten Midtbøen; Christophersen, Asbjørg S; Øiestad, Elisabeth

    2015-07-01

    Quantitative determination of anti-epileptic drug concentrations is of great importance in forensic toxicology cases. Although the drugs are not usually abused, they are important post-mortem cases where the question of both lack of compliance and accidental or deliberate poisoning might be raised. In addition these drugs can be relevant for driving under the influence cases. A reversed phase ultra-performance liquid chromatography-tandem mass spectrometry method has been developed for the quantitative analysis of the anti-epileptic compounds carbamazepine, carbamazepine-10,11-epoxide, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, 10-OH-carbazepine, phenobarbital, phenytoin, pregabalin, and topiramate in whole blood, using 0.1 mL sample volume with methaqualone as internal standard. Sample preparation was a simple protein precipitation with acetonitrile and methanol. The diluted supernatant was directly injected into the chromatographic system. Separation was performed on an Acquity UPLC® BEH Phenyl column with gradient elution and a mildly alkaline mobile phase. The mass spectrometric detection was performed in positive ion mode, except for phenobarbital, and multiple reaction monitoring was used for drug quantification. The limits of quantification for the different anti-epileptic drugs varied from 0.064 to 1.26 mg/L in blood, within-day and day-to-day relative standard deviations from 2.2 to 14.7% except for phenobarbital. Between-day variation for phenobarbital was 20.4% at the concentration level of 3.5 mg/L. The biases for all compounds were within ±17.5%. The recoveries ranged between 85 and 120%. The corrected matrix effects were 88-106% and 84-110% in ante-mortem and post-mortem whole blood samples, respectively. Copyright © 2014 John Wiley & Sons, Ltd.

  9. Time reversal and the neutron

    International Nuclear Information System (INIS)

    Chupp, T. E.; Cooper, R. L.; Coulter, K. P.; Freedman, S. J.; Fujikawa, B. K.; Jones, G. L.; Garcia, A.; Mumm, H. P.; Nico, J. S.; Thompson, A. K.; Trull, C.; Wietfeldt, F. E.; Wilkerson, J. F.

    2013-01-01

    We have measured the triple correlation D n >/J n ·(β e x p-hat ν ) with a polarized cold-neutron beam (Mumm et al., Phys Rev Lett 107:102301, 2011; Chupp et al., Phys Rev C 86:035505, 2012). A non-zero value of D can arise due to parity-even-time-reversal-odd interactions that imply CP violation. Final-state effects also contribute to D at the level of 10  − 5 and can be calculated with precision of 1 % or better. The D coefficient is uniquely sensitive to the imaginary part of the ratio of axial-vector and vector beta-decay amplitudes as well as to scalar and tensor interactions that could arise due to beyond-Standard-Model physics. Over 300 million proton-electron coincidence events were used in a blind analysis with the result D = [ − 0.94±1.89 (stat)±0.97(sys)]×10  − 4 . Assuming only vector and axial vector interactions in beta decay, our result can be interpreted as a measure of the phase of the axial-vector coupling relative to the vector coupling, φ AV = 180.012 ° ± 0.028 °. This result also improves constrains on certain non-VA interactions.

  10. Reverse transcriptase inhibitors as microbicides.

    Science.gov (United States)

    Lewi, Paul; Heeres, Jan; Ariën, Kevin; Venkatraj, Muthusamy; Joossens, Jurgen; Van der Veken, Pieter; Augustyns, Koen; Vanham, Guido

    2012-01-01

    The CAPRISA 004 study in South Africa has accelerated the development of vaginal and rectal microbicides containing antiretrovirals that target specific enzymes in the reproduction cycle of HIV, especially reverse transcriptase inhibitors (RTI). In this review we discuss the potential relevance of HIV-1 RTIs as microbicides, focusing in the nucleotide RTI tenofovir and six classes of nonnucleoside RTIs (including dapivirine, UC781, urea and thiourea PETTs, DABOs and a pyrimidinedione). Although tenofovir and dapivirine appear to be most advanced in clinical trials as potential microbicides, several issues remain unresolved, e.g., the importance of nonhuman primates as a "gatekeeper" for clinical trials, the emergence and spread of drug-resistant mutants, the combination of microbicides that target different phases of viral reproduction and the accessibility to microbicides in low-income countries. Thus, here we discuss the latest research on RTI as microbicides in the light of the continuing spread of the HIV pandemic from the point of view of medicinal chemistry, virological, and pharmaceutical studies.

  11. Reversible hypothyroidism and Whipple's disease

    Directory of Open Access Journals (Sweden)

    Tran Huy A

    2006-05-01

    Full Text Available Abstract Background The major cause of primary hypothyroidism is autoimmune mediated with progressive and permanent destruction of the thyroid gland resulting in life-long replacement therapy. Treatable and reversible hypothyroidism is unusual and here forth is such a case due to infection of the thyroid gland with Tropheryma whippleii, Whipple disease. Case presentation A 45 year-old female presented with symptoms and signs consistent with primary hypothyroidism, which was also confirmed biochemically. Her response to thyroxine replacement therapy was poor however, requiring a significantly elevated amount. Further investigation revealed the presence of Whipple's disease involving the gastrointestinal trace and possibly the thyroid gland. Her thyroxine requirement decreased drastically following appropriate antimicrobial therapy for Whipple's disease to the extent that it was ceased. Thyrotropin releasing hormone testing in the steady state suggested there was diminished thyroid reserve due to Whipple's disease. Conclusion This is the first ante-mortem case report studying the possible involvement of the thyroid gland by Whipple's disease. Despite the normalization of her thyroid function test biochemically after antibiotic therapy, there is diminished thyroid reserve thus requiring close and regular monitoring.

  12. Time reversal and the neutron

    Energy Technology Data Exchange (ETDEWEB)

    Chupp, T. E., E-mail: chupp@umich.edu; Cooper, R. L.; Coulter, K. P. [Univeristy of Michigan (United States); Freedman, S. J.; Fujikawa, B. K. [University of California and Lawrence Berkeley Laboratory (United States); Jones, G. L. [Hamilton College (United States); Garcia, A. [University of Washington (United States); Mumm, H. P.; Nico, J. S.; Thompson, A. K. [National Institute of Standards and Technology (United States); Trull, C.; Wietfeldt, F. E. [Tulane University (United States); Wilkerson, J. F. [University of North Carolina (United States); Collaboration: emiT II Collaboration

    2013-03-15

    We have measured the triple correlation D/J{sub n}{center_dot}({beta}{sub e} x p-hat{sub {nu}}) with a polarized cold-neutron beam (Mumm et al., Phys Rev Lett 107:102301, 2011; Chupp et al., Phys Rev C 86:035505, 2012). A non-zero value of D can arise due to parity-even-time-reversal-odd interactions that imply CP violation. Final-state effects also contribute to D at the level of 10{sup - 5} and can be calculated with precision of 1 % or better. The D coefficient is uniquely sensitive to the imaginary part of the ratio of axial-vector and vector beta-decay amplitudes as well as to scalar and tensor interactions that could arise due to beyond-Standard-Model physics. Over 300 million proton-electron coincidence events were used in a blind analysis with the result D = [ - 0.94{+-}1.89 (stat){+-}0.97(sys)] Multiplication-Sign 10{sup - 4}. Assuming only vector and axial vector interactions in beta decay, our result can be interpreted as a measure of the phase of the axial-vector coupling relative to the vector coupling, {phi}{sub AV} = 180.012 Degree-Sign {+-} 0.028 Degree-Sign . This result also improves constrains on certain non-VA interactions.

  13. Why has reversal of the actin-myosin cross-bridge cycle not been observed experimentally?

    KAUST Repository

    Loiselle, D. S.; Tran, K.; Crampin, E. J.; Curtin, N. A.

    2010-01-01

    We trace the history of attempts to determine whether the experimentally observed diminution of metabolic energy expenditure when muscles lengthen during active contraction is consistent with reversibility of biochemical reactions and, in particular

  14. Multiple reversal olfactory learning in honeybees

    Directory of Open Access Journals (Sweden)

    Theo Mota

    2010-07-01

    Full Text Available In multiple reversal learning, animals trained to discriminate a reinforced from a non-reinforced stimulus are subjected to various, successive reversals of stimulus contingencies (e.g. A+ vs. B-, A- vs. B+, A+ vs. B-. This protocol is useful to determine whether or not animals learn to learn and solve successive discriminations faster (or with fewer errors with increasing reversal experience. Here we used the olfactory conditioning of proboscis extension reflex to study how honeybees Apis mellifera perform in a multiple reversal task. Our experiment contemplated four consecutive differential conditioning phases involving the same odors (A+ vs. B- to A- vs. B+ to A+ vs. B- to A- vs. B+. We show that bees in which the weight of reinforced or non-reinforced stimuli was similar mastered the multiple olfactory reversals. Bees which failed the task exhibited asymmetric responses to reinforced and non-reinforced stimuli, thus being unable to rapidly reverse stimulus contingencies. Efficient reversers did not improve their successive discriminations but rather tended to generalize their choice to both odors at the end of conditioning. As a consequence, both discrimination and reversal efficiency decreasedalong experimental phases. This result invalidates a learning-to-learn effect and indicates that bees do not only respond to the actual stimulus contingencies but rather combine these with an average of past experiences with the same stimuli.  

  15. Online Reverse Auctions for Procurement of Services

    NARCIS (Netherlands)

    U.L. Radkevitch (Uladzimir)

    2008-01-01

    textabstractOnline reverse auctions, in which a buyer seeks to select a supplier and suppliers compete for contracts by bidding online, revolutionized corporate procurement early this century. Shortly after they had been pioneered by General Electric, many companies rushed to adopt reverse auctions

  16. Vibrational dynamics of ice in reverse micelles

    NARCIS (Netherlands)

    Dokter, A.M.; Petersen, C.; Woutersen, S.; Bakker, H.J.

    2008-01-01

    he ultrafast vibrational dynamics of HDO:D2O ice at 180 K in anionic reverse micelles is studied by midinfrared femtosecond pump-probe spectroscopy. Solutions containing reverse micelles are cooled to low temperatures by a fast-freezing procedure. The heating dynamics of the micellar solutions is

  17. Reversible logic gates on Physarum Polycephalum

    International Nuclear Information System (INIS)

    Schumann, Andrew

    2015-01-01

    In this paper, we consider possibilities how to implement asynchronous sequential logic gates and quantum-style reversible logic gates on Physarum polycephalum motions. We show that in asynchronous sequential logic gates we can erase information because of uncertainty in the direction of plasmodium propagation. Therefore quantum-style reversible logic gates are more preferable for designing logic circuits on Physarum polycephalum

  18. Magnetic reversals from planetary dynamo waves.

    Science.gov (United States)

    Sheyko, Andrey; Finlay, Christopher C; Jackson, Andrew

    2016-11-24

    A striking feature of many natural dynamos is their ability to undergo polarity reversals. The best documented example is Earth's magnetic field, which has reversed hundreds of times during its history. The origin of geomagnetic polarity reversals lies in a magnetohydrodynamic process that takes place in Earth's core, but the precise mechanism is debated. The majority of numerical geodynamo simulations that exhibit reversals operate in a regime in which the viscosity of the fluid remains important, and in which the dynamo mechanism primarily involves stretching and twisting of field lines by columnar convection. Here we present an example of another class of reversing-geodynamo model, which operates in a regime of comparatively low viscosity and high magnetic diffusivity. This class does not fit into the paradigm of reversal regimes that are dictated by the value of the local Rossby number (the ratio of advection to Coriolis force). Instead, stretching of the magnetic field by a strong shear in the east-west flow near the imaginary cylinder just touching the inner core and parallel to the axis of rotation is crucial to the reversal mechanism in our models, which involves a process akin to kinematic dynamo waves. Because our results are relevant in a regime of low viscosity and high magnetic diffusivity, and with geophysically appropriate boundary conditions, this form of dynamo wave may also be involved in geomagnetic reversals.

  19. Reverse engineering of the robot base platform

    International Nuclear Information System (INIS)

    Anwar A Rahman; Azizul Rahman A Aziz; Mohd Arif Hamzah; Muhd Nor Atan; Fadil Ismail; Rosli Darmawan

    2009-01-01

    The robot base platform used to place the robotic arm version 2 was imported through a local company. The robot base platform is used as a reference for reverse egineering development for a smaller size robot. The paper will discuss the reverse engineering design process and parameters involved in the development of the robot base platform. (Author)

  20. Reversal of laryngotracheal separation in paediatric patients.

    LENUS (Irish Health Repository)

    Young, Orla

    2012-02-01

    OBJECTIVE: Laryngotracheal separation (LTS) is an effective and reliable definitive treatment for intractable aspiration. A major advantage of this treatment for intractable aspiration is its\\' potential reversibility. Should the underlying disorder improve, a reversal of the procedure may be attempted. This has been successfully achieved in the adult population. To our knowledge, no previous cases have been reported of successful reversal of LTS in children. METHODS: A retrospective review from 2003 to 2010 identified four cases of intractable aspiration treated with LTS in our department. Two of these patients displayed objective evidence of sufficient recovery of their underlying aspiration to consider reversal. Patient selection for reversal was dependent upon successful oral intake for 9 months along with videofluoroscopic evidence of normal or minimally impaired swallow. RESULTS: Two children who were successfully treated for intractable aspiration with LTS demonstrated objective evidence of recovery sufficient to attempt reversal. Both children underwent successful surgical reversal of LTS using a cricotracheal resection with end-to-end anastamosis, similar to that used in treatment of subglottic stenosis. Both children can now tolerate oral diet and their speech and language development is in line with their overall developmental level. CONCLUSIONS: Laryngotracheal separation is an effective and reliable definitive treatment for intractable aspiration facilitating protection of the airway and allowing safe swallowing with unimpeded respiration, but with the major drawback of loss of phonation. To our knowledge, we document the first two cases of successful LTS reversal in children.

  1. Observation of the reversed current effect

    International Nuclear Information System (INIS)

    Jones, I.R.; Silawatshananai, C.

    1979-05-01

    The paper describes an observation of the reversed current effect, and its consequences, in a 'stabilized' Z-pinch. Magnetic probe measurements and holographic interferometry were used to follow the development of a reversed current layer and to pinpoint its location in the outer region of the pinched plasma column. The subsequent ejection of the outer plasma layer was observed using fast photography

  2. Magnetic reversals from planetary dynamo waves

    DEFF Research Database (Denmark)

    Sheyko, Andrey; Finlay, Chris; Jackson, Andrew

    2016-01-01

    A striking feature of many natural dynamos is their ability to undergo polarity reversals. The best documented example is Earth's magnetic field, which has reversed hundreds of times during its history. The origin of geomagnetic polarity reversals lies in a magnetohydrodynamic process that takes ...... to kinematic dynamo waves. Because our results are relevant in a regime of low viscosity and high magnetic diffusivity, and with geophysically appropriate boundary conditions, this form of dynamo wave may also be involved in geomagnetic reversals.......A striking feature of many natural dynamos is their ability to undergo polarity reversals. The best documented example is Earth's magnetic field, which has reversed hundreds of times during its history. The origin of geomagnetic polarity reversals lies in a magnetohydrodynamic process that takes...... place in Earth's core, but the precise mechanism is debated. The majority of numerical geodynamo simulations that exhibit reversals operate in a regime in which the viscosity of the fluid remains important, and in which the dynamo mechanism primarily involves stretching and twisting of field lines...

  3. Kronisk ileus efter iatrogen reversering af tyndtarmen

    DEFF Research Database (Denmark)

    Pedersen, Mark Ellebaek; Rahr, Hans B; Mahdi, Bassam

    2010-01-01

    We report a case of inadvertent reversal of the entire small intestine leading to severe complications and long-standing ileus. The clinical diagnosis was confirmed by magnetic resonance imaging and laparotomy. The patient was cured by surgical re-reversal of the bowel. Care should be taken to ma...... the bowel ends when multiple simultaneous bowel resections are performed....

  4. Probabilistic Reversible Automata and Quantum Automata

    OpenAIRE

    Golovkins, Marats; Kravtsev, Maksim

    2002-01-01

    To study relationship between quantum finite automata and probabilistic finite automata, we introduce a notion of probabilistic reversible automata (PRA, or doubly stochastic automata). We find that there is a strong relationship between different possible models of PRA and corresponding models of quantum finite automata. We also propose a classification of reversible finite 1-way automata.

  5. Reversed shear Alfven eigenmode stabilization by localized electron cyclotron heating

    Energy Technology Data Exchange (ETDEWEB)

    Van Zeeland, M A; Hyatt, A W; Lohr, J; Petty, C C [General Atomics, PO Box 85608 San Diego, CA 92186-5608 (United States); Heidbrink, W W [University of California-Irvine, Irvine, CA 92697 (United States); Nazikian, R; Solomon, W M; Gorelenkov, N N; Kramer, G J [Princeton Plasma Physics Laboratory, Princeton, NJ 08543-0451 (United States); Austin, M E [University of Texas-Austin, Austin, TX 78712 (United States); Berk, H L [Institute for Fusion Studies, University of Texas at Austin, Austin, TX 78712 (United States); Holcomb, C T; Makowski, M A [Lawrence Livermore National Laboratory, Livermore, CA (United States); McKee, G R [University of Wisconsin-Madison, Madison, WI 53726 (United States); Sharapov, S E [Euratom/UKAEA Fusion Association, Culham, Abingdon, Oxfordshire, OX14 3DB (United Kingdom); Rhodes, T L [University of California-Los Angeles, Los Angeles, California, 90095 (United States)], E-mail: vanzeeland@fusion.gat.com

    2008-03-15

    Reversed shear Alfven eigenmode (RSAE) activity in DIII-D is stabilized by electron cyclotron heating (ECH) applied near the minimum of the magnetic safety factor (q{sub min}) in neutral beam heated discharges with reversed-magnetic shear. The degree of RSAE stabilization, fast ion density and the volume averaged neutron production (S{sub n}) are highly dependent on ECH deposition location relative to q{sub min}. While discharges with ECH stabilization of RSAEs have higher S{sub n} and more peaked fast ion profiles than discharges with significant RSAE activity, neutron production remains strongly reduced (up to 60% relative to TRANSP predictions assuming classical fast ion transport) even when RSAEs are stabilized.

  6. Designing Novel Quaternary Quantum Reversible Subtractor Circuits

    Science.gov (United States)

    Haghparast, Majid; Monfared, Asma Taheri

    2018-01-01

    Reversible logic synthesis is an important area of current research because of its ability to reduce energy dissipation. In recent years, multiple valued logic has received great attention due to its ability to reduce the width of the reversible circuit which is a main requirement in quantum technology. Subtractor circuits are between major components used in quantum computers. In this paper, we will discuss the design of a quaternary quantum reversible half subtractor circuit using quaternary 1-qudit, 2-qudit Muthukrishnan-Stroud and 3-qudit controlled gates and a 2-qudit Generalized quaternary gate. Then a design of a quaternary quantum reversible full subtractor circuit based on the quaternary half subtractor will be presenting. The designs shall then be evaluated in terms of quantum cost, constant input, garbage output, and hardware complexity. The proposed quaternary quantum reversible circuits are the first attempt in the designing of the aforementioned subtractor.

  7. Parkinson’s disease managing reversible neurodegeneration

    Science.gov (United States)

    Hinz, Marty; Stein, Alvin; Cole, Ted; McDougall, Beth; Westaway, Mark

    2016-01-01

    Traditionally, the Parkinson’s disease (PD) symptom course has been classified as an irreversible progressive neurodegenerative disease. This paper documents 29 PD and treatment-induced systemic depletion etiologies which cause and/or exacerbate the seven novel primary relative nutritional deficiencies associated with PD. These reversible relative nutritional deficiencies (RNDs) may facilitate and accelerate irreversible progressive neurodegeneration, while other reversible RNDs may induce previously undocumented reversible pseudo-neurodegeneration that is hiding in plain sight since the symptoms are identical to the symptoms being experienced by the PD patient. Documented herein is a novel nutritional approach for reversible processes management which may slow or halt irreversible progressive neurodegenerative disease and correct reversible RNDs whose symptoms are identical to the patient’s PD symptoms. PMID:27103805

  8. Estimation and uncertainty of reversible Markov models.

    Science.gov (United States)

    Trendelkamp-Schroer, Benjamin; Wu, Hao; Paul, Fabian; Noé, Frank

    2015-11-07

    Reversibility is a key concept in Markov models and master-equation models of molecular kinetics. The analysis and interpretation of the transition matrix encoding the kinetic properties of the model rely heavily on the reversibility property. The estimation of a reversible transition matrix from simulation data is, therefore, crucial to the successful application of the previously developed theory. In this work, we discuss methods for the maximum likelihood estimation of transition matrices from finite simulation data and present a new algorithm for the estimation if reversibility with respect to a given stationary vector is desired. We also develop new methods for the Bayesian posterior inference of reversible transition matrices with and without given stationary vector taking into account the need for a suitable prior distribution preserving the meta-stable features of the observed process during posterior inference. All algorithms here are implemented in the PyEMMA software--http://pyemma.org--as of version 2.0.

  9. Drift reversal capability in helical systems

    International Nuclear Information System (INIS)

    Yokoyama, M.; Itoh, K.; Okamura, S.

    2002-10-01

    The maximum-J (J is the second adiabatic invariant) capability, i.e., the drift reversal capability, is examined in quasi-axisymmetric (QAS) stellarators and quasi-poloidally symmetric (QPS) stellarators as a possible mechanism for turbulent transport suppression. Due to the existence of non-axisymmetry of the magnetic field strength in QAS configurations, a local maximum of J is created to cause the drift reversal. The increase of magnetic shear in finite beta equilibria also has favorable effect in realizing the drift reversal. The radial variation of the uniform magnetic field component plays a crucial role for the drift reversal in a QPS configuration. Thus, the drift reversal capability and its external controllability are demonstrated for QAS and QPS stellarators, by which the impact of magnetic configuration on turbulent transport can be studied in experiments. (author)

  10. Drift reversal capability in helical systems

    International Nuclear Information System (INIS)

    Yokoyama, M.; Itoh, K.; Okamura, S.; Matsuoka, K.; Nakajima, N.; Itoh, S.-I.; Neilson, G.H.; Zarnstorff, M.C.; Rewoldt, G.

    2003-01-01

    The maximum-J (J is the second adiabatic invariant) capability, i.e., the drift reversal capability, is examined in quasi-axisymmetric (QAS) stellarators and quasi-poloidally symmetric (QPS) stellarators as a possible mechanism for turbulent transport suppression. Due to the existence of non-axisymmetry of the magnetic field strength in QAS configurations, a local maximum of J is created to cause the drift reversal. The increase of magnetic shear in finite beta equilibria also has favorable effect in realizing the drift reversal. The radial variation of the uniform magnetic field component plays a crucial role for the drift reversal in a QPS configuration. Thus, the drift reversal capability and its external controllability are demonstrated for QAS and QPS stellarators, by which the impact of magnetic configuration on turbulent transport can be studied in experiments. (author)

  11. Reversed field pinch ignition requirements

    International Nuclear Information System (INIS)

    Werley, K.A.

    1991-01-01

    Plasma models are described and used to calculated numerically the transport confinement (nτ E ) requirements and steady state operation points for both the reversed field pinch (RFP) and the tokamak. The models are used to examine the CIT tokamak ignition conditions and the RFP experimental and ignition conditions. Physics differences between RFPs and tokamaks and their consequences for a D-T ignition machine are discussed. Compared with a tokamak, the ignition RFP has many physics advantages, including Ohmic heating to ignition (no need for auxiliary heating systems), higher beta, lower ignition current, less sensitivity of ignition requirements to impurity effects, no hard disruptions (associated with beta or density limits) and successful operation with high radiation fractions (f RAD ∼ 0.95). These physics advantages, coupled with important engineering advantages associated with lower external magnetic field, larger aspect ratios and smaller plasma cross-sections, translate to significant cost reductions for both ignition and reactor applications. The primary drawback of the RFP is the uncertainty that the present scaling will extrapolate to reactor regimes. Devices that are under construction should go a long way toward resolving this scaling uncertainty. The 4 MA ZTH is expected to extend the nτ E transport scaling data by three orders of magnitude above the results of ZT-40M, and, if the present scaling holds, ZTH is expected to achieve a D-T equivalent scientific energy breakeven, Q = 1. A base case RFP ignition point is identified with a plasma current of 8.1 MA and no auxiliary heating. (author). 19 refs, 11 figs, 3 tabs

  12. Reversals and collisions optimize protein exchange in bacterial swarms

    Energy Technology Data Exchange (ETDEWEB)

    Amiri, Aboutaleb; Harvey, Cameron; Buchmann, Amy; Christley, Scott; Shrout, Joshua D.; Aranson, Igor S.; Alber, Mark

    2017-03-01

    Swarming groups of bacteria coordinate their behavior by self-organizing as a population to move over surfaces in search of nutrients and optimal niches for colonization. Many open questions remain about the cues used by swarming bacteria to achieve this self-organization. While chemical cue signaling known as quorum sensing is well-described, swarming bacteria often act and coordinate on time scales that could not be achieved via these extracellular quorum sensing cues. Here, cell-cell contact-dependent protein exchange is explored as amechanism of intercellular signaling for the bacterium Myxococcus xanthus. A detailed biologically calibrated computational model is used to study how M. xanthus optimizes the connection rate between cells and maximizes the spread of an extracellular protein within the population. The maximum rate of protein spreading is observed for cells that reverse direction optimally for swarming. Cells that reverse too slowly or too fast fail to spread extracellular protein efficiently. In particular, a specific range of cell reversal frequencies was observed to maximize the cell-cell connection rate and minimize the time of protein spreading. Furthermore, our findings suggest that predesigned motion reversal can be employed to enhance the collective behavior of biological synthetic active systems.

  13. Development of zero conditioning procedure for coal reverse flotation

    Energy Technology Data Exchange (ETDEWEB)

    D.P. Patil; J.S. Laskowski [University of British Columbia, Vancouver, BC (Canada). Mining Engineering Department

    2008-04-15

    The zero conditioning method was developed to facilitate the flotation of gangue minerals in the reverse coal flotation process. Batch and continuous methods were developed to maintain the zero conditioning principle during reverse flotation. Batch zero conditioning was achieved by adding the required amount of DTAB in one step, as soon as the air was introduced into the system. The continuous zero conditioning method involves uninterrupted addition of DTAB through a specially built sparger in the form of aerosol during the flotation experiment. This produces active bubbles that carry collector. The addition of DTAB in the form of aerosol during reverse flotation proved to be better in reducing the ash of a sub-bituminous (LS-26) coal from 34.7% to 22.9% with a froth product (gangue) yield of 36.8% without any depressant. In the presence of coal depressant (dextrin, 0.5 kg/t), the ash content of LS-26 coal was reduced from 34.7% to 16.5% at a clean coal yield of 55%, whereas the conventional (forward) flotation with fuel oil provided a clean coal containing 16.5% ash with only 29.2% yield. These results prove that flotation of gangue minerals is very much improved by maintaining zero conditioning time conditions in a coal reverse flotation process.

  14. A gene network simulator to assess reverse engineering algorithms.

    Science.gov (United States)

    Di Camillo, Barbara; Toffolo, Gianna; Cobelli, Claudio

    2009-03-01

    In the context of reverse engineering of biological networks, simulators are helpful to test and compare the accuracy of different reverse-engineering approaches in a variety of experimental conditions. A novel gene-network simulator is presented that resembles some of the main features of transcriptional regulatory networks related to topology, interaction among regulators of transcription, and expression dynamics. The simulator generates network topology according to the current knowledge of biological network organization, including scale-free distribution of the connectivity and clustering coefficient independent of the number of nodes in the network. It uses fuzzy logic to represent interactions among the regulators of each gene, integrated with differential equations to generate continuous data, comparable to real data for variety and dynamic complexity. Finally, the simulator accounts for saturation in the response to regulation and transcription activation thresholds and shows robustness to perturbations. It therefore provides a reliable and versatile test bed for reverse engineering algorithms applied to microarray data. Since the simulator describes regulatory interactions and expression dynamics as two distinct, although interconnected aspects of regulation, it can also be used to test reverse engineering approaches that use both microarray and protein-protein interaction data in the process of learning. A first software release is available at http://www.dei.unipd.it/~dicamill/software/netsim as an R programming language package.

  15. pH Gradient Reversal: An Emerging Hallmark of Cancers.

    Science.gov (United States)

    Sharma, Mohit; Astekar, Madhusudan; Soi, Sonal; Manjunatha, Bhari S; Shetty, Devi C; Radhakrishnan, Raghu

    2015-01-01

    Several tumors exhibit pH gradient reversal, with acidification of extracellular pH (pHe) and alkalinization of intracellular pH (pHi). The pH gradient reversal is evident even during the preliminary stages of tumorigenesis and is crucial for survival and propagation of tumors, irrespective of their pathology, genetics and origins. Moreover, this hallmark seems to be present ubiquitously in all malignant tumors. Based on these facts, we propose a new emerging hallmark of cancer "pH gradient reversal". Normalizing pH gradient reversal through inhibition of various proton transporters such as Na(+)-H(+) exchanger (NHE), Vacuolar-type H(+)-ATPase (V-ATPase), H(+)/K(+)-ATPases and carbonic anhydrases (CAs) has demonstrated substantial therapeutic benefits. Indeed, inhibition of NHE1 is now being regarded as the latest concept in cancer treatment. A recent patent deals with the utilization of cis-Urocanic acid to acidify the pHi and induce apoptosis in tumors. Another patent reports therapeutic benefit by inhibiting Lactate Dehydrogenase - 5 (LDH-5) in various cancers. Several patents have been formulated by designing drugs activated through acidic pHe providing a cancer specific action. The purpose of this review is to analyze the available literature and help design selective therapies that could be a valuable adjunct to the conventional therapies or even replace them.

  16. Rotational stability of a long field-reversed configuration

    International Nuclear Information System (INIS)

    Barnes, D. C.; Steinhauer, L. C.

    2014-01-01

    Rotationally driven modes of long systems with dominantly axial magnetic field are considered. We apply the incompressible model and order axial wavenumber small. A recently developed gyro-viscous model is incorporated. A one-dimensional equilibrium is assumed, but radial profiles are arbitrary. The dominant toroidal (azimuthal) mode numbers ℓ=1 and ℓ=2 modes are examined for a variety of non-reversed (B) and reversed profiles. Previous results for both systems with rigid rotor equilibria are reproduced. New results are obtained by incorporation of finite axial wavenumber and by relaxing the assumption of rigid electron and ion rotation. It is shown that the frequently troublesome ℓ=2 field reversed configuration (FRC) mode is not strongly affected by ion kinetic effects (in contrast to non-reversed cases) and is likely stabilized experimentally only by finite length effects. It is also shown that the ℓ=1 wobble mode has a complicated behavior and is affected by a variety of configuration and profile effects. The rotationally driven ℓ=1 wobble is completely stabilized by strong rotational shear, which is anticipated to be active in high performance FRC experiments. Thus, observed wobble modes in these systems are likely not driven by rotation alone

  17. Rotational stability of a long field-reversed configuration

    Energy Technology Data Exchange (ETDEWEB)

    Barnes, D. C., E-mail: coronadocon@msn.com; Steinhauer, L. C. [Tri Alpha Energy, Rancho Santa Margarita, California 92688 (United States)

    2014-02-15

    Rotationally driven modes of long systems with dominantly axial magnetic field are considered. We apply the incompressible model and order axial wavenumber small. A recently developed gyro-viscous model is incorporated. A one-dimensional equilibrium is assumed, but radial profiles are arbitrary. The dominant toroidal (azimuthal) mode numbers ℓ=1 and ℓ=2 modes are examined for a variety of non-reversed (B) and reversed profiles. Previous results for both systems with rigid rotor equilibria are reproduced. New results are obtained by incorporation of finite axial wavenumber and by relaxing the assumption of rigid electron and ion rotation. It is shown that the frequently troublesome ℓ=2 field reversed configuration (FRC) mode is not strongly affected by ion kinetic effects (in contrast to non-reversed cases) and is likely stabilized experimentally only by finite length effects. It is also shown that the ℓ=1 wobble mode has a complicated behavior and is affected by a variety of configuration and profile effects. The rotationally driven ℓ=1 wobble is completely stabilized by strong rotational shear, which is anticipated to be active in high performance FRC experiments. Thus, observed wobble modes in these systems are likely not driven by rotation alone.

  18. The reversal phase of the bone-remodeling cycle

    DEFF Research Database (Denmark)

    Delaisse, Jean-Marie

    2014-01-01

    coincides with decreased osteoblast recruitment and impaired initiation of bone formation, that is, uncoupling. Overall, this review stresses that coupling does not only depend on molecules able to activate osteogenesis, but that it also demands the presence of osteoprogenitors and ordered cell......The reversal phase couples bone resorption to bone formation by generating an osteogenic environment at remodeling sites. The coupling mechanism remains poorly understood, despite the identification of a number of 'coupling' osteogenic molecules. A possible reason is the poor attention...

  19. The reversal of the Sun's magnetic field in cycle 24

    OpenAIRE

    Mordvinov, Alexander V.; Pevtsov, Alexei A.; Bertello, Luca; Petrie, Gordon J. D.

    2016-01-01

    Analysis of synoptic data from the Vector Stokes Magnetograph (VSM) of the Synoptic Optical Long-term Investigations of the Sun (SOLIS) and the NASA/NSO Spectromagnetograph (SPM) at the NSO/Kitt Peak Vacuum Telescope facility shows that the reversals of solar polar magnetic fields exhibit elements of a stochastic process, which may include the development of specific patterns of emerging magnetic flux, and the asymmetry in activity between northern and southern hemispheres. The presence of su...

  20. Magnetization reversal and 1/H law in highly anisotropic materials

    International Nuclear Information System (INIS)

    Barbara, B.; Uehara, M.

    1978-01-01

    A model has been developed for the coercive field, based on the concept of creation and annihilation of domain-wall kinks. This model accounts for the Barkhausen jumps and leads to a new process of magnetization reversal involving simultaneously the pinning and nucleation mechanisms. It is characterized by an activation energy proportional to the reciprocal magnetic field H -1 . Such dependence has been observed in different kinds of materials and therefore seems to be general. (author)

  1. Reversibility: An Engineer's Point of View

    Energy Technology Data Exchange (ETDEWEB)

    Berest, Pierre [LMS, ecole Polytechnique (France)

    2012-07-01

    Reversibility is the most consistent option in a democratic country. However reversibility may also have several drawbacks which must be identified and mitigated. Reversibility of a geological repository is a relatively new idea in France. The 1991 law dedicated to nuclear waste management considered reversibility as a possible option. Fifteen years later, the 2006 law mandated that a deep repository must be reversible and that the exact content of this notion should be defined by a new law to be discussed by the Parliament in 2015. Reversibility was not a concern put forward by engineers. It clearly originated from a societal demand sponsored and formulated by the Parliament. Since 1991, the exact meaning of this mandate progressively became more precise. In the early days, reversibility meant the technical and financial capability to retrieve the wastes from the repository, at least for some period of time after being emplaced. Progressively, a broader definition, suggested by Andra, was accepted: reversibility also means that a disposal facility should be operated in such a way that a stepwise decision-making process is possible. At each step, society must be able to decide to proceed to the next step, to pause or to reverse a step. Several benefits can be expected from a reversible repository. Some technical safety concerns may be only recognised after waste emplacement. Radioactive wastes may become a resource whose recoverability is desirable. Regulations may change, alternative waste treatment or better disposal techniques may be developed, or the need to modify a component of the facility may arise. Looking back at how chemical or domestic wastes were managed some 50 years ago easily underscores that it is not unreasonable to hope for significant advances in the future. For scientists and engineers, reversibility proves to have several other merits. To design and build a good repository, time is needed. The operator of a mine or of an oil field knows that

  2. THE IMPORTANCE OF REVERSE LOGISTICS

    OpenAIRE

    Elmas, Güldem; Erdoğmuş, Fevzi

    2011-01-01

    How do companies differentiate themselves when operating in industries where most, if not all firms offer high quality products and customer service at the time of sale? For many products, a customer’s relationship with the product’s manufacturer does not end with product purchase. In fact, this relationship can be significantly influenced by the activities that occur after purchase, during the entire period of product ownership. After sales services can encompass multiple activities, i...

  3. Glucotoxicity promotes aberrant activation and mislocalization of Ras-related C3 botulinum toxin substrate 1 [Rac1] and metabolic dysfunction in pancreatic islet β-cells: reversal of such metabolic defects by metformin.

    Science.gov (United States)

    Baidwan, Sartaj; Chekuri, Anil; Hynds, DiAnna L; Kowluru, Anjaneyulu

    2017-11-01

    Emerging evidence suggests that long-term exposure of insulin-secreting pancreatic β-cells to hyperglycemic (HG; glucotoxic) conditions promotes oxidative stress, which, in turn, leads to stress kinase activation, mitochondrial dysfunction, loss of nuclear structure and integrity and cell apoptosis. Original observations from our laboratory have proposed that Rac1 plays a key regulatory role in the generation of oxidative stress and downstream signaling events culminating in the onset of dysfunction of pancreatic β-cells under the duress of metabolic stress. However, precise molecular and cellular mechanisms underlying the metabolic roles of hyperactive Rac1 remain less understood. Using pharmacological and molecular biological approaches, we now report mistargetting of biologically-active Rac1 [GTP-bound conformation] to the nuclear compartment in clonal INS-1 cells, normal rat islets and human islets under HG conditions. Our findings also suggest that such a signaling step is independent of post-translational prenylation of Rac1. Evidence is also presented to highlight novel roles for sustained activation of Rac1 in HG-induced expression of Cluster of Differentiation 36 [CD36], a fatty acid transporter protein, which is implicated in cell apoptosis. Finally, our findings suggest that metformin, a biguanide anti-diabetic drug, at a clinically relevant concentration, prevents β-cell defects [Rac1 activation, nuclear association, CD36 expression, stress kinase and caspase-3 activation, and loss in metabolic viability] under the duress of glucotoxicity. Potential implications of these findings in the context of novel and direct regulation of islet β-cell function by metformin are discussed.

  4. Docking and 3-D QSAR studies on indolyl aryl sulfones. Binding mode exploration at the HIV-1 reverse transcriptase non-nucleoside binding site and design of highly active N-(2-hydroxyethyl)carboxamide and N-(2-hydroxyethyl)carbohydrazide derivatives.

    Science.gov (United States)

    Ragno, Rino; Artico, Marino; De Martino, Gabriella; La Regina, Giuseppe; Coluccia, Antonio; Di Pasquali, Alessandra; Silvestri, Romano

    2005-01-13

    Three-dimensional quantitative structure-activity relationship (3-D QSAR) studies and docking simulations were developed on indolyl aryl sulfones (IASs), a class of novel HIV-1 non-nucleoside reverse transcriptase (RT) inhibitors (Silvestri, et al. J. Med. Chem. 2003, 46, 2482-2493) highly active against wild type and some clinically relevant resistant strains (Y181C, the double mutant K103N-Y181C, and the K103R-V179D-P225H strain, highly resistant to efavirenz). Predictive 3-D QSAR models using the combination of GRID and GOLPE programs were obtained using a receptor-based alignment by means of docking IASs into the non-nucleoside binding site (NNBS) of RT. The derived 3-D QSAR models showed conventional correlation (r(2)) and cross-validated (q(2)) coefficients values ranging from 0.79 to 0.93 and from 0.59 to 0.84, respectively. All described models were validated by an external test set compiled from previously reported pyrryl aryl sulfones (Artico, et al. J. Med. Chem. 1996, 39, 522-530). The most predictive 3-D QSAR model was then used to predict the activity of novel untested IASs. The synthesis of six designed derivatives (prediction set) allowed disclosure of new IASs endowed with high anti-HIV-1 activities.

  5. Visual hydrogen detector with variable reversibility

    Science.gov (United States)

    Muradov, Nazim (Inventor)

    2011-01-01

    Methods, processes and compositions are provided for a visual or chemochromic hydrogen-detector with variable or tunable reversible color change. The working temperature range for the hydrogen detector is from minus 100.degree. C. to plus 500.degree. C. A hydrogen-sensitive pigment, including, but not limited to, oxides, hydroxides and polyoxo-compounds of tungsten, molybdenum, vanadium, chromium and combinations thereof, is combined with nano-sized metal activator particles and preferably, coated on a porous or woven substrate. In the presence of hydrogen, the composition rapidly changes its color from white or light-gray or light-tan to dark gray, navy-blue or black depending on the exposure time and hydrogen concentration in the medium. After hydrogen exposure ceases, the original color of the hydrogen-sensitive pigment is restored, and the visual hydrogen detector can be used repeatedly. By changing the composition of the hydrogen-sensitive pigment, the time required for its complete regeneration is varied from a few seconds to several days.

  6. Double quick, double click reversible peptide "stapling".

    Science.gov (United States)

    Grison, Claire M; Burslem, George M; Miles, Jennifer A; Pilsl, Ludwig K A; Yeo, David J; Imani, Zeynab; Warriner, Stuart L; Webb, Michael E; Wilson, Andrew J

    2017-07-01

    The development of constrained peptides for inhibition of protein-protein interactions is an emerging strategy in chemical biology and drug discovery. This manuscript introduces a versatile, rapid and reversible approach to constrain peptides in a bioactive helical conformation using BID and RNase S peptides as models. Dibromomaleimide is used to constrain BID and RNase S peptide sequence variants bearing cysteine (Cys) or homocysteine ( h Cys) amino acids spaced at i and i + 4 positions by double substitution. The constraint can be readily removed by displacement of the maleimide using excess thiol. This new constraining methodology results in enhanced α-helical conformation (BID and RNase S peptide) as demonstrated by circular dichroism and molecular dynamics simulations, resistance to proteolysis (BID) as demonstrated by trypsin proteolysis experiments and retained or enhanced potency of inhibition for Bcl-2 family protein-protein interactions (BID), or greater capability to restore the hydrolytic activity of the RNAse S protein (RNase S peptide). Finally, use of a dibromomaleimide functionalized with an alkyne permits further divergent functionalization through alkyne-azide cycloaddition chemistry on the constrained peptide with fluorescein, oligoethylene glycol or biotin groups to facilitate biophysical and cellular analyses. Hence this methodology may extend the scope and accessibility of peptide stapling.

  7. N-Acetylcysteine Reverses Cocaine Induced Metaplasticity

    Science.gov (United States)

    Moussawi, Khaled; Pacchioni, Alejandra; Moran, Megan; Olive, M. Foster; Gass, Justin T.; Lavin, Antonieta; Kalivas, Peter W

    2009-01-01

    Cocaine addiction is characterized by an impaired ability to develop adaptive behaviors that can compete with cocaine seeking, implying a deficit in the ability to induce plasticity in cortico-accumbens circuitry critical for regulating motivated behavior. RWe found that rats withdrawn from cocaine self-administration had a marked in vivo deficit in the ability to develop long-term potentation (LTP) and depression (LTD) in the nucleus accumbens core subregion following stimulation of prefrontal cortex. N-acetylcysteine treatment prevents relapse in animal models and craving in humans by activating cystine-glutamate exchange and thereby stimulating extrasynaptic metabotropic glutamate receptors (mGluR). N-acetylcysteine treatment restored the ability to induce LTP and LTD by indirectly stimulating mGluR2/3 and mGluR5, respectively. Cocaine self-administration induces metaplasticity that inhibits the further induction of synaptic plasticity, and this impairment can be reversed by N-acetylcysteine, a drug that also prevents relapse. PMID:19136971

  8. Reverse transcriptase inhibitors as potential colorectal microbicides.

    Science.gov (United States)

    Herrera, Carolina; Cranage, Martin; McGowan, Ian; Anton, Peter; Shattock, Robin J

    2009-05-01

    We investigated whether reverse transcriptase (RT) inhibitors (RTI) can be combined to inhibit human immunodeficiency virus type 1 (HIV-1) infection of colorectal tissue ex vivo as part of a strategy to develop an effective rectal microbicide. The nucleotide RTI (NRTI) PMPA (tenofovir) and two nonnucleoside RTI (NNRTI), UC-781 and TMC120 (dapivirine), were evaluated. Each compound inhibited the replication of the HIV isolates tested in TZM-bl cells, peripheral blood mononuclear cells, and colorectal explants. Dual combinations of the three compounds, either NRTI-NNRTI or NNRTI-NNRTI combinations, were more active than any of the individual compounds in both cellular and tissue models. Combinations were key to inhibiting infection by NRTI- and NNRTI-resistant isolates in all models tested. Moreover, we found that the replication capacities of HIV-1 isolates in colorectal explants were affected by single point mutations in RT that confer resistance to RTI. These data demonstrate that colorectal explants can be used to screen compounds for potential efficacy as part of a combination microbicide and to determine the mucosal fitness of RTI-resistant isolates. These findings may have important implications for the rational design of effective rectal microbicides.

  9. Reversible myocardial ischaemia or irreversible myocardial fibrosis

    International Nuclear Information System (INIS)

    Mathey, D.; Hanrath, P.; Kupper, W.; Bleifeld, W.; Montz, R.; Knop, J.; Stritzke, P.; Kroeger, E.; Bleese, N.

    1978-01-01

    The results of biphasis 201 thallium ( 201 Tl) scanning were compared with those of coronary arteriography, left ventricular angiography and stress ECG in 56 patients with coronary artery disease and six with no evidence of heart disease. There were 104 201 Tl defects, 50 of them reversible. The defects were always located in the area supplied by a critically stenotic coronary artery. Correlation of regional wall motion with 201 Tl activity demonstrated that in all forms of abnormal wall motion there was either ischaemia or fibrosis. The resting LV angiogram thus does not make it possible to distinguish between myocardial ischaemia and fibrosis. Taking the LV angiogram as a standard, the rate of false-positive 201 Tl scintigrams was 5%, that of false-negative ones 23%. The biphasic 201 Tl scintigram was more sensitive than the stress ECG in detecting myocardial ischaemia. It furthermore made it possible to localize the ischaemic (or fibrotic) region within the LV and to estimate its size. (orig.) [de

  10. Chemical reactions in reverse micelle systems

    Science.gov (United States)

    Matson, Dean W.; Fulton, John L.; Smith, Richard D.; Consani, Keith A.

    1993-08-24

    This invention is directed to conducting chemical reactions in reverse micelle or microemulsion systems comprising a substantially discontinuous phase including a polar fluid, typically an aqueous fluid, and a microemulsion promoter, typically a surfactant, for facilitating the formation of reverse micelles in the system. The system further includes a substantially continuous phase including a non-polar or low-polarity fluid material which is a gas under standard temperature and pressure and has a critical density, and which is generally a water-insoluble fluid in a near critical or supercritical state. Thus, the microemulsion system is maintained at a pressure and temperature such that the density of the non-polar or low-polarity fluid exceeds the critical density thereof. The method of carrying out chemical reactions generally comprises forming a first reverse micelle system including an aqueous fluid including reverse micelles in a water-insoluble fluid in the supercritical state. Then, a first reactant is introduced into the first reverse micelle system, and a chemical reaction is carried out with the first reactant to form a reaction product. In general, the first reactant can be incorporated into, and the product formed in, the reverse micelles. A second reactant can also be incorporated in the first reverse micelle system which is capable of reacting with the first reactant to form a product.

  11. Reversible Lithium Neurotoxicity: Review of the Literature

    Science.gov (United States)

    Netto, Ivan

    2012-01-01

    Objective: Lithium neurotoxicity may be reversible or irreversible. Reversible lithium neurotoxicity has been defined as cases of lithium neurotoxicity in which patients recovered without any permanent neurologic sequelae, even after 2 months of an episode of lithium toxicity. Cases of reversible lithium neurotoxicity differ in clinical presentation from those of irreversible lithium neurotoxicity and have important implications in clinical practice. This review aims to study the clinical presentation of cases of reversible lithium neurotoxicity. Data Sources: A comprehensive electronic search was conducted in the following databases: MEDLINE (PubMed), 1950 to November 2010; PsycINFO, 1967 to November 2010; and SCOPUS (EMBASE), 1950 to November 2010. MEDLINE and PsycINFO were searched by using the OvidSP interface. Study Selection: A combination of the following search terms was used: lithium AND adverse effects AND central nervous system OR neurologic manifestation. Publications cited include articles concerned with reversible lithium neurotoxicity. Data Extraction: The age, sex, clinical features, diagnostic categories, lithium doses, serum lithium levels, precipitating factors, and preventive measures of 52 cases of reversible lithium neurotoxicity were extracted. Data Synthesis: Among the 52 cases of reversible lithium neurotoxicity, patients ranged in age from 10 to 80 years and a greater number were female (P = .008). Most patients had affective disorders, schizoaffective disorders, and/or depression (P lithium levels were less than or equal to 1.5 mEq/L (P lithium, underlying brain pathology, abnormal tissue levels, specific diagnostic categories, and elderly populations were some of the precipitating factors reported for reversible lithium neurotoxicity. The preventive measures were also described. Conclusions: Reversible lithium neurotoxicity presents with a certain clinical profile and precipitating factors for which there are appropriate

  12. Reversible lithium neurotoxicity: review of the literatur.

    Science.gov (United States)

    Netto, Ivan; Phutane, Vivek H

    2012-01-01

    Lithium neurotoxicity may be reversible or irreversible. Reversible lithium neurotoxicity has been defined as cases of lithium neurotoxicity in which patients recovered without any permanent neurologic sequelae, even after 2 months of an episode of lithium toxicity. Cases of reversible lithium neurotoxicity differ in clinical presentation from those of irreversible lithium neurotoxicity and have important implications in clinical practice. This review aims to study the clinical presentation of cases of reversible lithium neurotoxicity. A comprehensive electronic search was conducted in the following databases: MEDLINE (PubMed), 1950 to November 2010; PsycINFO, 1967 to November 2010; and SCOPUS (EMBASE), 1950 to November 2010. MEDLINE and PsycINFO were searched by using the OvidSP interface. A combination of the following search terms was used: lithium AND adverse effects AND central nervous system OR neurologic manifestation. Publications cited include articles concerned with reversible lithium neurotoxicity. The age, sex, clinical features, diagnostic categories, lithium doses, serum lithium levels, precipitating factors, and preventive measures of 52 cases of reversible lithium neurotoxicity were extracted. Among the 52 cases of reversible lithium neurotoxicity, patients ranged in age from 10 to 80 years and a greater number were female (P = .008). Most patients had affective disorders, schizoaffective disorders, and/or depression (P lithium levels were less than or equal to 1.5 mEq/L (P lithium, underlying brain pathology, abnormal tissue levels, specific diagnostic categories, and elderly populations were some of the precipitating factors reported for reversible lithium neurotoxicity. The preventive measures were also described. Reversible lithium neurotoxicity presents with a certain clinical profile and precipitating factors for which there are appropriate preventive measures. This recognition will help in early diagnosis and prompt treatment of

  13. From reverse transcription to human brain tumors

    Directory of Open Access Journals (Sweden)

    Dmitrenko V. V.

    2013-05-01

    Full Text Available Reverse transcriptase from avian myeloblastosis virus (AMV was the subject of the study, from which the investi- gations of the Department of biosynthesis of nucleic acids were started. Production of AMV in grams quantities and isolation of AMV reverse transcriptase were established in the laboratory during the seventies of the past cen- tury and this initiated research on the cDNA synthesis, cloning and investigation of the structure and functions of the eukaryotic genes. Structures of salmon insulin and insulin-like growth factor (IGF family genes and their transcripts were determined during long-term investigations. Results of two modern techniques, microarray-ba- sed hybridization and SAGE, were used for the identification of the genes differentially expressed in astrocytic gliomas and human normal brain. Comparison of SAGE results on the genes overexpressed in glioblastoma with the results of microarray analysis revealed a limited number of common genes. 105 differentially expressed genes, common to both methods, can be included in the list of candidates for the molecular typing of glioblastoma. The first experiments on the classification of glioblastomas based on the data of the 20 genes expression were conducted by using of artificial neural network analysis. The results of these experiments showed that the expression profiles of these genes in 224 glioblastoma samples and 74 normal brain samples could be according to the Koho- nen’s maps. The CHI3L1 and CHI3L2 genes of chitinase-like cartilage protein were revealed among the most overexpressed genes in glioblastoma, which could have prognostic and diagnostic potential. Results of in vitro experiments demonstrated that both proteins, CHI3L1 and CHI3L2, may initiate the phosphorylation of ERK1/ ERK2 and AKT kinases leading to the activation of MAPK/ERK1/2 and PI3K/AKT signaling cascades in human embryonic kidney 293 cells, human glioblastoma U87MG, and U373 cells. The new human cell line

  14. Aminocaproic Acid and Tranexamic Acid Fail to Reverse Dabigatran-Induced Coagulopathy.

    Science.gov (United States)

    Levine, Michael; Huang, Margaret; Henderson, Sean O; Carmelli, Guy; Thomas, Stephen H

    In recent years, dabigatran has emerged as a popular alternative to warfarin for treatment of atrial fibrillation. If rapid reversal is required, however, no reversal agent has clearly been established. The primary purpose of this manuscript was to evaluate the efficacy of tranexamic acid and aminocaproic acid as agents to reverse dabigatran-induced coagulopathy. Rats were randomly assigned to 6 groups. Each rat received either dabigatran or oral placebo, followed by saline, tranexamic acid, or aminocaproic acid. An activated clotting test was used to measure the coagulopathy. Neither tranexamic acid nor aminocaproic acid successfully reversed dabigatran-induced coagulopathy. In this rodent model of dabigatran-induced coagulopathy, neither tranexamic acid nor aminocaproic acid were able to reverse the coagulopathy.

  15. A point mutation in the DNA-binding domain of HPV-2 E2 protein increases its DNA-binding capacity and reverses its transcriptional regulatory activity on the viral early promoter

    Directory of Open Access Journals (Sweden)

    Gao Chen

    2012-02-01

    Full Text Available Abstract Background The human papillomavirus (HPV E2 protein is a multifunctional DNA-binding protein. The transcriptional activity of HPV E2 is mediated by binding to its specific binding sites in the upstream regulatory region of the HPV genomes. Previously we reported a HPV-2 variant from a verrucae vulgaris patient with huge extensive clustered cutaneous, which have five point mutations in its E2 ORF, L118S, S235P, Y287H, S293R and A338V. Under the control of HPV-2 LCR, co-expression of the mutated HPV E2 induced an increased activity on the viral early promoter. In the present study, a series of mammalian expression plasmids encoding E2 proteins with one to five amino acid (aa substitutions for these mutations were constructed and transfected into HeLa, C33A and SiHa cells. Results CAT expression assays indicated that the enhanced promoter activity was due to the co-expressions of the E2 constructs containing A338V mutation within the DNA-binding domain. Western blots analysis demonstrated that the transiently transfected E2 expressing plasmids, regardless of prototype or the A338V mutant, were continuously expressed in the cells. To study the effect of E2 mutations on its DNA-binding activity, a serial of recombinant E2 proteins with various lengths were expressed and purified. Electrophoresis mobility shift assays (EMSA showed that the binding affinity of E2 protein with A338V mutation to both an artificial probe with two E2 binding sites or HPV-2 and HPV-16 promoter-proximal LCR sequences were significantly stronger than that of the HPV-2 prototype E2. Furthermore, co-expression of the construct containing A338V mutant exhibited increased activities on heterologous HPV-16 early promoter P97 than that of prototype E2. Conclusions These results suggest that the mutation from Ala to Val at aa 338 is critical for E2 DNA-binding and its transcriptional regulation.

  16. Parallelization of Reversible Ripple-carry Adders

    DEFF Research Database (Denmark)

    Thomsen, Michael Kirkedal; Axelsen, Holger Bock

    2009-01-01

    The design of fast arithmetic logic circuits is an important research topic for reversible and quantum computing. A special challenge in this setting is the computation of standard arithmetical functions without the generation of \\emph{garbage}. Here, we present a novel parallelization scheme...... wherein $m$ parallel $k$-bit reversible ripple-carry adders are combined to form a reversible $mk$-bit \\emph{ripple-block carry adder} with logic depth $\\mathcal{O}(m+k)$ for a \\emph{minimal} logic depth $\\mathcal{O}(\\sqrt{mk})$, thus improving on the $mk$-bit ripple-carry adder logic depth $\\mathcal...

  17. Reversible perspective and splitting in time.

    Science.gov (United States)

    Hart, Helen Schoenhals

    2012-01-01

    The element of time--the experience of it and the defensive use of it--is explored in conjunction with the use of reversible perspective as a psychotic defense. Clinical material from a long analysis illustrates how a psychotic patient used the reversible perspective, with its static splitting, to abolish the experience of time. When he improved and the reversible perspective became less effective for him, he replaced it with a more dynamic splitting mechanism using time gaps. With further improvement, the patient began to experience the passage of time, and along with it the excruciating pain of separation, envy, and loss.

  18. Performance of the reverse Helmbold universal portfolio

    Science.gov (United States)

    Tan, Choon Peng; Kuang, Kee Seng; Lee, Yap Jia

    2017-04-01

    The universal portfolio is an important investment strategy in a stock market where no stochastic model is assumed for the stock prices. The zero-gradient set of the objective function estimating the next-day portfolio which contains the reverse Kullback-Leibler order-alpha divergence is considered. From the zero-gradient set, the explicit, reverse Helmbold universal portfolio is obtained. The performance of the explicit, reverse Helmbold universal portfolio is studied by running them on some stock-price data sets from the local stock exchange. It is possible to increase the wealth of the investor by using these portfolios in investment.

  19. Time reversibility in the quantum frame

    Energy Technology Data Exchange (ETDEWEB)

    Masot-Conde, Fátima [Escuela Superior Ingenieros, Dpt. Física Aplicada III, Universidad de Sevilla Isla Mágica, 41092- Sevilla (Spain)

    2014-12-04

    Classic Mechanics and Electromagnetism, conventionally taken as time-reversible, share the same concept of motion (either of mass or charge) as the basis of the time reversibility in their own fields. This paper focuses on the relationship between mobile geometry and motion reversibility. The goal is to extrapolate the conclusions to the quantum frame, where matter and radiation behave just as elementary mobiles. The possibility that the asymmetry of Time (Time’s arrow) is an effect of a fundamental quantum asymmetry of elementary particles, turns out to be a consequence of the discussion.

  20. Refractory reverse amblyopia with atropine penalization

    Directory of Open Access Journals (Sweden)

    Preeti Ajit Patil

    2010-01-01

    Full Text Available Pharmacological penalization with atropine has been shown to be equally effective as conventional occlusion therapy in the treatment of amblyopia in children. Reverse amblyopia of the sound eye with atropine penalization has been reported before, but is more common in cases where the effect is augmented with optical penalization and is mostly reversible. We report a case of reverse amblyopia with atropine penalization, in a 4-year-old girl, which was refractory to treatment. This report highlights the need for strict monitoring of the vision in the sound eye and regular follow-up in children undergoing amblyopia treatment.